鼎湖鳞伞菌丝体多糖的发酵条件优化、分离纯化、抗肿瘤活性及其机制的研究
|
摘要
蘑菇作为人类的食物和药物在世界上已经有数千年的使用历史了。蘑菇中含有丰富的营养物质和医药用途物质,包括大量的碳水化合物、蛋白质、维生素,硫胺素,核黄素,抗坏血酸,维生素D,以及矿物质等。现代医学研究表明,蘑菇多糖具有免疫调节、抗肿瘤、抗氧化、降胆固醇、降血糖、抗菌和抗病毒、抗过敏和抗炎、保肝护肝和肠道益生等功能。鼎湖鳞伞(Pholiota dinghuensis Bi)为中国特有种,(?)Pholiota属中的一个新种,1985年发现于我国广东省。目前关于鼎湖鳞伞菌丝体多糖的研究尚未见报道。因此,本论文主要对鼎湖鳞伞菌丝体的发酵条件优化、多糖分离纯化、理化性质研究、体内抗CCl4诱导小鼠急性肝损伤、体外抗癌活性筛选、抑制人乳腺癌MCF-7细胞体外增殖以及诱导其凋亡的信号通路进行了研究。主要研究结果如下：
1液体发酵制备鼎湖鳞伞菌丝体粗多糖的条件优化
首先通过单因素试验筛选了发酵产生鼎湖鳞伞菌丝体多糖的培养基成分以及发酵条件。初步确定了适于鼎湖鳞伞菌丝体多糖的最佳培养基配方为复合碳源(葡萄糖和玉米粉)40g/L、复合氮源(蛋白胨和酵母膏)4g/L、KH2P041g/L和MgSO41.5g/L,最佳的接种量为15%(v/v),培养温度为25℃,摇床转速为140rpm。
然后在单因素优化基础上采用部分组成因子设计(FFD)试验研究了不同培养基成分对鼎湖鳞伞菌丝体多糖的显著性影响。结果发现,葡萄糖、玉米粉和酵母膏对鼎湖鳞伞菌丝体多糖的产量最为显著。进一步采用爬坡试验得到葡萄糖、玉米粉和酵母膏浓度中心点分别为35、10和5g/L。并以此为中心点,采用中心组成因子设计(CCD)试验对显著性影响因素的浓度进行优化。结果表明,当葡萄糖、玉米粉和酵母膏的浓度分别为36.0、11.8和5.4g/L时,鼎湖鳞伞菌丝体多糖产量达到757±38mg/L,与预测值较为一致。统计分析表明该模型能有效的预测鼎湖鳞伞菌丝体多糖的产量。
液体发酵得到的菌丝体经干燥、粉碎、热水浸提、乙醇沉淀、离心,然后用丙酮和乙醚依次洗涤、干燥,得到鼎湖鳞伞菌丝体粗多糖。
2鼎湖鳞伞菌丝体多糖分离纯化与理化性质研究
采用DEAE-纤维素阴离子交换柱层析法对鼎湖鳞伞菌丝体粗多糖进行初步分离,并采用葡聚糖G-100凝胶过滤柱层析法对各个组分进一步纯化,得到鼎湖鳞伞菌丝体多糖纯化组分PDP-1、PDP-2和PDP-3共三个组分,得率分别为60.25%、23.69%和4.61%。采用分子排阻液相法进一步分析了PDP-1、PDP-2和PDP-3,结果发现三种纯化多糖是均一的组分,分子量分别为1.59×105、7.20×105和3.53x105Da。
采用苯酚-硫酸法、间羟联苯法、考马斯亮蓝法和氯化钡-明胶比色法测定了多糖样品中的总糖、糖醛酸、蛋白质和硫酸基含量,结果表明鼎湖鳞伞菌丝体粗多糖、PDP-1、PDP-2和PDP-3中总糖含量分别为86.95%、97.97%、94.46%和85.58%；在所测的各个多糖组分中,PDP-3含有较高的蛋白、糖醛酸和硫酸基含量。
通过糖腈乙酸酯衍生物气相色谱法测定了多糖样品的单糖组成。鼎湖鳞伞菌丝体粗多糖、PDP-1、PDP-2和PDP-3中的葡萄糖含量分别为92.54%、92.24%、88.65%和67.83%。对于粗多糖而言,阿拉伯糖、岩藻糖、木糖、甘露糖、葡萄糖、半乳糖的比例分别为2.18%、1.06%、1.48%、0.92%、92.54%和1.82%。三个纯化组分中,与PDP-1和PDP-2相比,PDP-3的单糖组成更为复杂,其中PDP-3中含有鼠李糖和木糖,而PDP-1和PDP-2没有被检测到,且PDP-3中的岩藻糖、甘露糖和半乳糖含量均比PDP-1和PDP-2中的含量高。
红外光谱扫描结果显示,鼎湖鳞伞菌丝体粗多糖以及各个纯化样品的吸收峰表明了所有样品均具有多糖特征。图谱中特征吸收峰表明PDP-2和PDP-3是酸性多糖和硫酸酯化多糖；同时证明了PDP-3可能是一种多糖和蛋白或肽的复合物。紫外光谱扫描结果表明鼎湖鳞伞菌丝体粗多糖及其各纯化组分在波长为280nm左右有不同程度的吸收峰,表明各样品均含有一定的蛋白或者肽,但是PDP-3的蛋白比其它组分含量更高。
3鼎湖鳞伞菌丝体粗多糖体内对CCl4诱导小鼠急性肝损伤的肝保护作用
采用四氯化碳诱导的小鼠急性肝损体内动物试验模型评价了鼎湖鳞伞菌丝体粗多糖肝保护作用。结果表明,鼎湖鳞伞菌丝体粗多糖能有效降低小鼠血清中的天门冬氨酸转移酶(AST)和丙氨酸转移酶(ALT)活性,并提高小鼠肝脏组织中SOD和GSH-Px的活性；同时研究发现,鼎湖鳞伞菌丝体粗多糖能抑制四氯化碳诱导的小鼠肝组织中丙二醛(MDA)的含量；小鼠肝组织切染色结果显示高剂量鼎湖鳞伞菌丝体粗多糖(每天200mg/kg体重)能明显减轻四氯化碳导致的小鼠肝脏组织浸染、细胞形态结构和颜色变化,达到阳性对照的保肝护肝效果。实验结果表明鼎湖鳞伞菌丝体粗多糖对四氯化碳诱导的小鼠急性肝损有明显的保护作用。
4鼎湖鳞伞菌丝体粗多糖及其纯化组分体外抑制肿瘤细胞增殖活性与机理
采用MTT法以人胃癌BGC-823细胞为模型,同时采用亚甲基蓝染色法以人肝癌HepG2细胞为模型,分别筛选了鼎湖鳞伞菌丝体粗多糖及其纯化组分(PDP-1、PDP-2和PDP-3)的体外肿瘤细胞增殖抑制活性。结果发现,PDP-3具有较好的体外抗肿瘤细胞增殖的活性。然后,以人乳腺MCF-10A细胞、人乳腺癌MDA-MB-231和MCF-7细胞株筛选了PDP-3体外对人乳腺细胞的增殖抑制活性。结果发现PDP-3对于非肿瘤化的人乳腺MCF-10A细胞没有明显增殖抑制作用,而对人乳腺癌MDA-MB-231和MCF-7细胞均具有非常显著增殖抑制作用；细胞划痕愈合试验结果表明PDP-3能有效降低MDA-MB-231细胞的浸染和转移能力。Western-blot试验结果发现,PDP-3能显著增加雌性激素依赖型的人乳腺癌MCF-7细胞中p21蛋白表达,同时能明显降低PCNA、CyclinD1和CDK4的蛋白表达。
5PDP-3体外诱导人乳腺癌MCF-7凋亡及其抗癌机理
采用Western-blot法测定了PDP-3处理对人乳腺癌MCF-7细胞中的Bcl-2、Bax、 Caspase-9、Caspase-3、p-p53、p-p38、ASK1、TRAF2以及细胞核和细胞之中的ER-α等蛋白的表达影响。结果发现,PDP-3处理激活了人乳腺癌MCF-7细胞中p38/MAPK通路,通过提高p21蛋白表达,降低人乳腺癌MCF-7细胞中与细胞增殖(PCNA)和细胞周期相关蛋白(Cyclin D1和CDK4)表达,从而有效抑制了细胞增殖；同时通过增加Bax和降低Bcl-2表达,以及激活Caspase家族蛋白(Caspase-9和Caspase-3)共同诱导人乳腺癌MCF-7细胞凋亡。上游蛋白表达结果证实PDP-3提高了p-p53、p-p38和ASKl蛋白表达,并降低TRAF2蛋白表达；同时研究发现,PDP-3处理能显著降低了人乳腺癌MCF-7细胞核和细胞质中雌激素受体ER-α蛋白的表达。TUNEL试验和DNA片段化试验结果分别证实了PDP-3能诱导人乳腺癌MCF-7细胞凋亡。结合本论文第五和六章实验结果,总结出PDP-3抗人乳腺癌MCF-7细胞的信号通路图。
Mushroom has been used as food and drugs for human in the world about several thousand years already, and many nutrients and compounds with medicinal use, including carbohydrates, protein, vitamins, thiamine, riboflavin, ascorbic acid, vitamin D, and minerals, etc, were found in the mushroom. Modern medical research shows that the mushroom polysaccharides possess the bioactivities of immunomodulatory, anti-tumor, antioxidant, cholesterol-lowering, hypoglycemic, anti-bacterial, anti-virus, anti-allergic and anti-inflammatory, hepatoprotectivity and intestinal prebiotics. Pholiota dinghuensis Bi is a new species in Pholiota family, and is only found in Guangdong Province of China. As a specific kind of mushroom, its bioactive polysaccharides should be paid more attention. However, little information is available compared with those of other Pholiota mushrooms. Therefore, studies about polysaccharide of from the mycelium of Pholiota dinghuensis Bi, on the optimization of fermentation conditions, separation and purification, physicochemical properties and in vivo hepatoprotective effects on CC14-induced acute liver injury, in vitro anticancer activities, prevention of cell proliferation and induction of apoptosis in human breast cancer MCF-7cells were studied. The main findings are as following:
1. Optimization of submerged fermentation conditions for crude PDP
Firstly, optical medium composition and fermentation conditions were screened by single factor experiments for the submerged fermentation of crude polysaccharide (PDP) from mycelia of Pholiota dingensis Bi. The primary conditions for crude PDP production were set as of SCS40g/L, SNS4g/L, inoculum volume15%(v/v), culture temperature25℃and shaking speed140rpm.
Based on the results of single factor experiments, a fractional factorial design (FFD) was initially employed to screen the most significant factors based on our previous study, and the glucose, corn flour and yeast extract were selected as the most significant factors. And then, a path of steepest ascent experiment was carried out for the suitable concentrations for the selected factors, and the central points of the concentrations of glucose, corn flour and yeast extract were set35,10and5g/L, respectively.
After that, a central composite design (CCD) of RSM was applied to study the optimal medium compositions for maximum PDP production. As results, the optimal conditions for crude PDP production were determined as (g/L):glucose36.0, corn flour11.8, peptone3.0, yeast extract5.4, KH2PO41.0and MgSO41.5. Using these optimal conditions, the crude PDP yield of757±38mg/L was obtained, which is in a good correlation with the prediction of this model. The statistical analysis of this model showed an effective prediction of the crude PDP.
Mycelia of Pholiota dingensis Bi were dried, powdered, and extracted by hot water. The supernatant were precipitated by ethanol, and then centrifuged. The precipitate were collected and dried for crude PDP.
2. Separation and purification, and physicochemical properties of PDP
Crude PDP was sequentially purified by DEAE-52cellulose ion-exchange chromatography and Sephadex G-100size-exclusion chromatography, then three fractions (PDP-1, PDP-2and PDP-3) were obtained, with a recovery rate of60.25%.23.69%and4.61%, respectively. PDP-1, PDP-2and PDP-3were further confirmed as homogeneous polysaccharides using HPGPC, and its relative molecular weight was1.59x105,7.20x105and3.53×105Da, respectively.
The contents of carbohydrate, uronic acid, protein and sulfate in polysaccharide samples were determined according to the reported methods of sulfuric acid-phenol coloration, the m-hydroxybiphenyl colourimetric procedure, coomassie brilliant blue coloration and barium chloride-gelatin, respectively. The contents of carbohydrate of crude PDP, PDP-1, PDP-2and PDP-3were86.95%,97.97%,94.46%and85.58%, respectively. In the purified fractions, PDP-3represents higher uronic acid, protein and sulfate content than PDP-1and PDP-3, indicating PDP-3was a complex of polysaccharide and protein or peptide.
The monosaccharide compositions of crude PDP and its purified fractions (PDP-1, PDP-2and PDP-3) were carried out by GC according to the methods of aldonitrile acetate derivatives. Notably, glucose was found to be the most abundant monosaccharide, in a ratio of92.54%,92.24%,88.65%and67.83%, respectively, for crude PDP, PDP-1, PDP-2and PDP-3. For crude PDP, it was composed of arabinose, fucose, xylose, mannose, glucose and galactose in relative percent of2.18,1.06,1.48,0.92,92.54and1.82, respectively. However, the monosaccharide composition of PDP-3was different from that of PDP-1or PDP-2. Interestingly, xylose and rhamnose were found only to be present in PDP-3. In addition, the contents of fucose, mannose and galactose in PDP-3were relatively higher than those in PDP-1or PDP-2.
The FT-IR spectra of crude PDP, PDP-1, PDP-2, and PDP-3were by the potassium bromide (KBr) pellet method. All the absorption peaks of tested samples indicated the characteristic absorptions of polysaccharides. Furthermore, specific absorbance of COO-and S=O indicated PDP-2and PDP-3were acidic polysaccharides and sulfated polysaccharides. What's more, the relative stronger absorption peak of N-H bending vibration might be related to the higher content of protein in PDP-3. UV spectrum results indicated that there was some protein absorption in all samples, but higher protein absorption in PDP-3was found.
3. In vivo hepatoprotective effects of crude PDP against carbon tetrachloride-induced acute liver injury in mice
The hepatoprotective effects of PDP against carbon tetrachloride (CC14)-induced acute liver damage in Kunming female mice were investigated. As a result, PDP-3significantly prevented the increase of serum ALT and AST activities, and enhanced the SOD and GSH-Px activities in CC14-induced mice. The formation and accumulation of MDA in the liver of CC14-induced mice was significantly prevented by the pretreatment of PDP-3. The histopathological results showed, pretreatment with crude PDP at200mg/kg BW per day restored from the CC14-induced liver jury, which depicted in the model control with marked and massive inflammation, infiltration and color changes of tissue, indicating a similar effect of pretreatment with silymarin in the positive control group. All the results showed that crude PDP represents a relative hepatoprotective effect against carbon tetrachloride (CC14)-induced acute liver damage in mice.
4. In vitro antiproliferative activities and its mechanism of PDPs to the human cancer cells
MTT assay for human gastric cancer BGC-823cells, and methylene blue staining for human liver cancer HepG2cells, were used to screen in vitro antiproliferative activities toward human tumor cells of crude PDP and its purified fractions (PDP-1, PDP-2and PDP-3). The results showed the PDP-3represented the highest antiproliferative activity than PDP-1and PDP-2. And then, human breast MCF-10A cells, human breast cancer MDA-MB-231and MCF-7cells were selected to screen the in vitro antiproliferative activity of PDP-3toward human breast cells. As a result, a little prevention of proliferation of MCF-10A cells was found when pretreated with PDP-3, while PDP-3showed significant antiproliferative activities toward human breast cancer MDA-MB-231and MCF-7cells. However, higher antiproliferative activity of PDP-3in estrogen-dependent human breast cancer MCF-7cell, when compared to the estrogen-independent human breast cancer MDA-MB-231cell. To further investigation showed PDP-3up-regulated the protein expression of p21and down-regulated the protein expression of PCNA and Cyclin D1and CDK4in human breast cancer MCF-7cells.
5. In vitro apoptosis of human breast cancer MCF-7cells and its mechanism induced by PDP-3
Western-blot analysis were used to determine the effect of protein expression of Bcl-2, Bax, Caspase-9, Caspase-3, p-p53, p-p38, ASK1, TRAF2, nuclear and plasmic ER-α in the human breast cancer MCF-7cells pretreated by PDP-3. The results showed the PDP-3activated p38/MAPK pathway in human breast cancer MCF-7cells. For the cell proliferation, PDP-3increased the p21protein expression and reduced human breast cancer MCF-7cells and cell proliferation (PCNA) and cell cycle-related protein (Cyclin D1and CDK4) expression; For the cell apoptosis, PDP-3increased Bax and lowered Bcl-2expression, and also activated the expression of Caspase family proteins (caspase-9and Caspase-3). Results of upstream protein expression showed PDP-3increased p-p53, p-p38and ASK1protein expression, and reduced the TRAF2protein expression. What's more, PDP-3down-regulated the protein expression of nuclear and plasmic ER-α in human breast cancer MCF-7cells. The results of TUNEL assay and DNA fragmentation confirmed the apoptosis of human breast cancer MCF-7cells pretreated by the PDP-3. The signaling pathway of PDP-3induced antiproliferation and apoptosis in human breast cancer MCF-7cells was summed up, based on all of the relative results in the fifth and sixth chapter of this thesis.
1液体发酵制备鼎湖鳞伞菌丝体粗多糖的条件优化
首先通过单因素试验筛选了发酵产生鼎湖鳞伞菌丝体多糖的培养基成分以及发酵条件。初步确定了适于鼎湖鳞伞菌丝体多糖的最佳培养基配方为复合碳源(葡萄糖和玉米粉)40g/L、复合氮源(蛋白胨和酵母膏)4g/L、KH2P041g/L和MgSO41.5g/L,最佳的接种量为15%(v/v),培养温度为25℃,摇床转速为140rpm。
然后在单因素优化基础上采用部分组成因子设计(FFD)试验研究了不同培养基成分对鼎湖鳞伞菌丝体多糖的显著性影响。结果发现,葡萄糖、玉米粉和酵母膏对鼎湖鳞伞菌丝体多糖的产量最为显著。进一步采用爬坡试验得到葡萄糖、玉米粉和酵母膏浓度中心点分别为35、10和5g/L。并以此为中心点,采用中心组成因子设计(CCD)试验对显著性影响因素的浓度进行优化。结果表明,当葡萄糖、玉米粉和酵母膏的浓度分别为36.0、11.8和5.4g/L时,鼎湖鳞伞菌丝体多糖产量达到757±38mg/L,与预测值较为一致。统计分析表明该模型能有效的预测鼎湖鳞伞菌丝体多糖的产量。
液体发酵得到的菌丝体经干燥、粉碎、热水浸提、乙醇沉淀、离心,然后用丙酮和乙醚依次洗涤、干燥,得到鼎湖鳞伞菌丝体粗多糖。
2鼎湖鳞伞菌丝体多糖分离纯化与理化性质研究
采用DEAE-纤维素阴离子交换柱层析法对鼎湖鳞伞菌丝体粗多糖进行初步分离,并采用葡聚糖G-100凝胶过滤柱层析法对各个组分进一步纯化,得到鼎湖鳞伞菌丝体多糖纯化组分PDP-1、PDP-2和PDP-3共三个组分,得率分别为60.25%、23.69%和4.61%。采用分子排阻液相法进一步分析了PDP-1、PDP-2和PDP-3,结果发现三种纯化多糖是均一的组分,分子量分别为1.59×105、7.20×105和3.53x105Da。
采用苯酚-硫酸法、间羟联苯法、考马斯亮蓝法和氯化钡-明胶比色法测定了多糖样品中的总糖、糖醛酸、蛋白质和硫酸基含量,结果表明鼎湖鳞伞菌丝体粗多糖、PDP-1、PDP-2和PDP-3中总糖含量分别为86.95%、97.97%、94.46%和85.58%；在所测的各个多糖组分中,PDP-3含有较高的蛋白、糖醛酸和硫酸基含量。
通过糖腈乙酸酯衍生物气相色谱法测定了多糖样品的单糖组成。鼎湖鳞伞菌丝体粗多糖、PDP-1、PDP-2和PDP-3中的葡萄糖含量分别为92.54%、92.24%、88.65%和67.83%。对于粗多糖而言,阿拉伯糖、岩藻糖、木糖、甘露糖、葡萄糖、半乳糖的比例分别为2.18%、1.06%、1.48%、0.92%、92.54%和1.82%。三个纯化组分中,与PDP-1和PDP-2相比,PDP-3的单糖组成更为复杂,其中PDP-3中含有鼠李糖和木糖,而PDP-1和PDP-2没有被检测到,且PDP-3中的岩藻糖、甘露糖和半乳糖含量均比PDP-1和PDP-2中的含量高。
红外光谱扫描结果显示,鼎湖鳞伞菌丝体粗多糖以及各个纯化样品的吸收峰表明了所有样品均具有多糖特征。图谱中特征吸收峰表明PDP-2和PDP-3是酸性多糖和硫酸酯化多糖；同时证明了PDP-3可能是一种多糖和蛋白或肽的复合物。紫外光谱扫描结果表明鼎湖鳞伞菌丝体粗多糖及其各纯化组分在波长为280nm左右有不同程度的吸收峰,表明各样品均含有一定的蛋白或者肽,但是PDP-3的蛋白比其它组分含量更高。
3鼎湖鳞伞菌丝体粗多糖体内对CCl4诱导小鼠急性肝损伤的肝保护作用
采用四氯化碳诱导的小鼠急性肝损体内动物试验模型评价了鼎湖鳞伞菌丝体粗多糖肝保护作用。结果表明,鼎湖鳞伞菌丝体粗多糖能有效降低小鼠血清中的天门冬氨酸转移酶(AST)和丙氨酸转移酶(ALT)活性,并提高小鼠肝脏组织中SOD和GSH-Px的活性；同时研究发现,鼎湖鳞伞菌丝体粗多糖能抑制四氯化碳诱导的小鼠肝组织中丙二醛(MDA)的含量；小鼠肝组织切染色结果显示高剂量鼎湖鳞伞菌丝体粗多糖(每天200mg/kg体重)能明显减轻四氯化碳导致的小鼠肝脏组织浸染、细胞形态结构和颜色变化,达到阳性对照的保肝护肝效果。实验结果表明鼎湖鳞伞菌丝体粗多糖对四氯化碳诱导的小鼠急性肝损有明显的保护作用。
4鼎湖鳞伞菌丝体粗多糖及其纯化组分体外抑制肿瘤细胞增殖活性与机理
采用MTT法以人胃癌BGC-823细胞为模型,同时采用亚甲基蓝染色法以人肝癌HepG2细胞为模型,分别筛选了鼎湖鳞伞菌丝体粗多糖及其纯化组分(PDP-1、PDP-2和PDP-3)的体外肿瘤细胞增殖抑制活性。结果发现,PDP-3具有较好的体外抗肿瘤细胞增殖的活性。然后,以人乳腺MCF-10A细胞、人乳腺癌MDA-MB-231和MCF-7细胞株筛选了PDP-3体外对人乳腺细胞的增殖抑制活性。结果发现PDP-3对于非肿瘤化的人乳腺MCF-10A细胞没有明显增殖抑制作用,而对人乳腺癌MDA-MB-231和MCF-7细胞均具有非常显著增殖抑制作用；细胞划痕愈合试验结果表明PDP-3能有效降低MDA-MB-231细胞的浸染和转移能力。Western-blot试验结果发现,PDP-3能显著增加雌性激素依赖型的人乳腺癌MCF-7细胞中p21蛋白表达,同时能明显降低PCNA、CyclinD1和CDK4的蛋白表达。
5PDP-3体外诱导人乳腺癌MCF-7凋亡及其抗癌机理
采用Western-blot法测定了PDP-3处理对人乳腺癌MCF-7细胞中的Bcl-2、Bax、 Caspase-9、Caspase-3、p-p53、p-p38、ASK1、TRAF2以及细胞核和细胞之中的ER-α等蛋白的表达影响。结果发现,PDP-3处理激活了人乳腺癌MCF-7细胞中p38/MAPK通路,通过提高p21蛋白表达,降低人乳腺癌MCF-7细胞中与细胞增殖(PCNA)和细胞周期相关蛋白(Cyclin D1和CDK4)表达,从而有效抑制了细胞增殖；同时通过增加Bax和降低Bcl-2表达,以及激活Caspase家族蛋白(Caspase-9和Caspase-3)共同诱导人乳腺癌MCF-7细胞凋亡。上游蛋白表达结果证实PDP-3提高了p-p53、p-p38和ASKl蛋白表达,并降低TRAF2蛋白表达；同时研究发现,PDP-3处理能显著降低了人乳腺癌MCF-7细胞核和细胞质中雌激素受体ER-α蛋白的表达。TUNEL试验和DNA片段化试验结果分别证实了PDP-3能诱导人乳腺癌MCF-7细胞凋亡。结合本论文第五和六章实验结果,总结出PDP-3抗人乳腺癌MCF-7细胞的信号通路图。
Mushroom has been used as food and drugs for human in the world about several thousand years already, and many nutrients and compounds with medicinal use, including carbohydrates, protein, vitamins, thiamine, riboflavin, ascorbic acid, vitamin D, and minerals, etc, were found in the mushroom. Modern medical research shows that the mushroom polysaccharides possess the bioactivities of immunomodulatory, anti-tumor, antioxidant, cholesterol-lowering, hypoglycemic, anti-bacterial, anti-virus, anti-allergic and anti-inflammatory, hepatoprotectivity and intestinal prebiotics. Pholiota dinghuensis Bi is a new species in Pholiota family, and is only found in Guangdong Province of China. As a specific kind of mushroom, its bioactive polysaccharides should be paid more attention. However, little information is available compared with those of other Pholiota mushrooms. Therefore, studies about polysaccharide of from the mycelium of Pholiota dinghuensis Bi, on the optimization of fermentation conditions, separation and purification, physicochemical properties and in vivo hepatoprotective effects on CC14-induced acute liver injury, in vitro anticancer activities, prevention of cell proliferation and induction of apoptosis in human breast cancer MCF-7cells were studied. The main findings are as following:
1. Optimization of submerged fermentation conditions for crude PDP
Firstly, optical medium composition and fermentation conditions were screened by single factor experiments for the submerged fermentation of crude polysaccharide (PDP) from mycelia of Pholiota dingensis Bi. The primary conditions for crude PDP production were set as of SCS40g/L, SNS4g/L, inoculum volume15%(v/v), culture temperature25℃and shaking speed140rpm.
Based on the results of single factor experiments, a fractional factorial design (FFD) was initially employed to screen the most significant factors based on our previous study, and the glucose, corn flour and yeast extract were selected as the most significant factors. And then, a path of steepest ascent experiment was carried out for the suitable concentrations for the selected factors, and the central points of the concentrations of glucose, corn flour and yeast extract were set35,10and5g/L, respectively.
After that, a central composite design (CCD) of RSM was applied to study the optimal medium compositions for maximum PDP production. As results, the optimal conditions for crude PDP production were determined as (g/L):glucose36.0, corn flour11.8, peptone3.0, yeast extract5.4, KH2PO41.0and MgSO41.5. Using these optimal conditions, the crude PDP yield of757±38mg/L was obtained, which is in a good correlation with the prediction of this model. The statistical analysis of this model showed an effective prediction of the crude PDP.
Mycelia of Pholiota dingensis Bi were dried, powdered, and extracted by hot water. The supernatant were precipitated by ethanol, and then centrifuged. The precipitate were collected and dried for crude PDP.
2. Separation and purification, and physicochemical properties of PDP
Crude PDP was sequentially purified by DEAE-52cellulose ion-exchange chromatography and Sephadex G-100size-exclusion chromatography, then three fractions (PDP-1, PDP-2and PDP-3) were obtained, with a recovery rate of60.25%.23.69%and4.61%, respectively. PDP-1, PDP-2and PDP-3were further confirmed as homogeneous polysaccharides using HPGPC, and its relative molecular weight was1.59x105,7.20x105and3.53×105Da, respectively.
The contents of carbohydrate, uronic acid, protein and sulfate in polysaccharide samples were determined according to the reported methods of sulfuric acid-phenol coloration, the m-hydroxybiphenyl colourimetric procedure, coomassie brilliant blue coloration and barium chloride-gelatin, respectively. The contents of carbohydrate of crude PDP, PDP-1, PDP-2and PDP-3were86.95%,97.97%,94.46%and85.58%, respectively. In the purified fractions, PDP-3represents higher uronic acid, protein and sulfate content than PDP-1and PDP-3, indicating PDP-3was a complex of polysaccharide and protein or peptide.
The monosaccharide compositions of crude PDP and its purified fractions (PDP-1, PDP-2and PDP-3) were carried out by GC according to the methods of aldonitrile acetate derivatives. Notably, glucose was found to be the most abundant monosaccharide, in a ratio of92.54%,92.24%,88.65%and67.83%, respectively, for crude PDP, PDP-1, PDP-2and PDP-3. For crude PDP, it was composed of arabinose, fucose, xylose, mannose, glucose and galactose in relative percent of2.18,1.06,1.48,0.92,92.54and1.82, respectively. However, the monosaccharide composition of PDP-3was different from that of PDP-1or PDP-2. Interestingly, xylose and rhamnose were found only to be present in PDP-3. In addition, the contents of fucose, mannose and galactose in PDP-3were relatively higher than those in PDP-1or PDP-2.
The FT-IR spectra of crude PDP, PDP-1, PDP-2, and PDP-3were by the potassium bromide (KBr) pellet method. All the absorption peaks of tested samples indicated the characteristic absorptions of polysaccharides. Furthermore, specific absorbance of COO-and S=O indicated PDP-2and PDP-3were acidic polysaccharides and sulfated polysaccharides. What's more, the relative stronger absorption peak of N-H bending vibration might be related to the higher content of protein in PDP-3. UV spectrum results indicated that there was some protein absorption in all samples, but higher protein absorption in PDP-3was found.
3. In vivo hepatoprotective effects of crude PDP against carbon tetrachloride-induced acute liver injury in mice
The hepatoprotective effects of PDP against carbon tetrachloride (CC14)-induced acute liver damage in Kunming female mice were investigated. As a result, PDP-3significantly prevented the increase of serum ALT and AST activities, and enhanced the SOD and GSH-Px activities in CC14-induced mice. The formation and accumulation of MDA in the liver of CC14-induced mice was significantly prevented by the pretreatment of PDP-3. The histopathological results showed, pretreatment with crude PDP at200mg/kg BW per day restored from the CC14-induced liver jury, which depicted in the model control with marked and massive inflammation, infiltration and color changes of tissue, indicating a similar effect of pretreatment with silymarin in the positive control group. All the results showed that crude PDP represents a relative hepatoprotective effect against carbon tetrachloride (CC14)-induced acute liver damage in mice.
4. In vitro antiproliferative activities and its mechanism of PDPs to the human cancer cells
MTT assay for human gastric cancer BGC-823cells, and methylene blue staining for human liver cancer HepG2cells, were used to screen in vitro antiproliferative activities toward human tumor cells of crude PDP and its purified fractions (PDP-1, PDP-2and PDP-3). The results showed the PDP-3represented the highest antiproliferative activity than PDP-1and PDP-2. And then, human breast MCF-10A cells, human breast cancer MDA-MB-231and MCF-7cells were selected to screen the in vitro antiproliferative activity of PDP-3toward human breast cells. As a result, a little prevention of proliferation of MCF-10A cells was found when pretreated with PDP-3, while PDP-3showed significant antiproliferative activities toward human breast cancer MDA-MB-231and MCF-7cells. However, higher antiproliferative activity of PDP-3in estrogen-dependent human breast cancer MCF-7cell, when compared to the estrogen-independent human breast cancer MDA-MB-231cell. To further investigation showed PDP-3up-regulated the protein expression of p21and down-regulated the protein expression of PCNA and Cyclin D1and CDK4in human breast cancer MCF-7cells.
5. In vitro apoptosis of human breast cancer MCF-7cells and its mechanism induced by PDP-3
Western-blot analysis were used to determine the effect of protein expression of Bcl-2, Bax, Caspase-9, Caspase-3, p-p53, p-p38, ASK1, TRAF2, nuclear and plasmic ER-α in the human breast cancer MCF-7cells pretreated by PDP-3. The results showed the PDP-3activated p38/MAPK pathway in human breast cancer MCF-7cells. For the cell proliferation, PDP-3increased the p21protein expression and reduced human breast cancer MCF-7cells and cell proliferation (PCNA) and cell cycle-related protein (Cyclin D1and CDK4) expression; For the cell apoptosis, PDP-3increased Bax and lowered Bcl-2expression, and also activated the expression of Caspase family proteins (caspase-9and Caspase-3). Results of upstream protein expression showed PDP-3increased p-p53, p-p38and ASK1protein expression, and reduced the TRAF2protein expression. What's more, PDP-3down-regulated the protein expression of nuclear and plasmic ER-α in human breast cancer MCF-7cells. The results of TUNEL assay and DNA fragmentation confirmed the apoptosis of human breast cancer MCF-7cells pretreated by the PDP-3. The signaling pathway of PDP-3induced antiproliferation and apoptosis in human breast cancer MCF-7cells was summed up, based on all of the relative results in the fifth and sixth chapter of this thesis.
引文
[1]Moradali M F, Mostafavi H, Ghods S, et al. Immunomodulating and anticancer agents in the realm of macromycetes fungi (macrofungi) [J]. International Immunopharmacology,2007,7(6):701-724
[2]Wasser S P. Current findings, future trends, and unsolved problems in studies of medicinal mushrooms [J]. Applied Microbiology and Biotechnology,2011,89(5):1323-1332
[3]Miles P G, Chang S T. Mushroom biology-concise basics and current developments [J]. Singapore: World Scientific,1997,144.
[4]陈娟,苏开美.食用菌遗传育种及种质鉴定研究进展[J].中国食用菌,2008,27(5)：3-8.
[5]Rathee S, Rathee D, Rathee D, et al. Mushrooms as therapeutic agents [J]. Revista Brasileira de Farmacognosia-Brazilian Journal of Pharmacognosy.2012,22(2):459-474.
[6]Wasser S P. Medicinal mushroom science:history, current Status, future trends, and unsolved problems [J]. International Journal of Medicinal Mushrooms,2010,12(1):1-16
[7]Dotan N, Wasser S P, Mahajna J. The culinary-medicinal mushroom Coprinus comatus as a natural antiandrogenic modulator [J]. Integrative Cancer Therapies,2011,10(2):148-59.
[8]Mattila P, Suonpaa K, Piironen V. Functional properties of edible mushrooms [J]. Nutrition,2000, 16(7/8):694-696.
[9]Zaidman B Z, Yassin M, Mahajna J, et al. Medicinal mushroom modulators of molecular targets as cancer therapeutics [J]. Applied Microbiology and Biotechnology,2005,67(4):453-468.
[10]Dai Y C, Yang Z L, Cui B K, et al. Species diversity and utilization of medicinal mushrooms and Fungi in China (Review) [J]. International Journal for Medicinal Mushrooms,2009,11(3): 287-302.
[11]Aida F M N A, Shuhaimi M, Yazid M, et al. Mushroom as a potential source of prebiotics:a review [J]. Trends in Food Science & Technology,2009,20(11-12):567-575
[12]Chang S T. Global impact of edible and medicinal mushrooms on human welfare in the 21st century: nongreen revolution [J]. International Journal for Medicinal Mushrooms,1999,1:1-8.
[13]Wasser S P, Weis A L. Medicinal properties of substances occurring in higher Basidiomycetes mushrooms:current perspectives (review) [J]. International Journal for Medicinal Mushrooms, 1999,1:31-62.
[14]Mizuno T. The extraction and development of antitumor-active polysaccharides from medicinal mushrooms in Japan (review) [J]. International Journal for Medicinal Mushrooms,1999,1: 9-29.
[15]Reshetnikov S V, Tan K K. Higher Basidiomycota as source of antitumor and immunostimulating polysaccharides [J]. International Journal for Medicinal Mushrooms,2001,3:361-394.
[16]Wasser S P. Medicinal mushrooms:ancient traditions, contemporary knowledge, and scientific enquiries [J]. International Journal for Medicinal Mushrooms,2007,9(3/4):187-189.
[17]Van Griensven L J L D. Culinary-medicinal mushrooms:must action be taken? [J] International Journal for Medicinal Mushrooms,2009,11(3):281-286.
[18]Bohn J A, BeMiller J N. (1-3)-β-D-glucans as biological response modifiers:a review of structure-functional activity relationships [J]. Carbohydrate Polymers,1995,28:3-14.
[19]Sarkar S, Koga J, Whitley R J, et al. Antiviral effect of the extract of culture medium of Lentinus edodes mycelia on the replication of herpes simplex virus type 1 [J]. Antiviral Research,1993, 20(4):293-303.
[20]Matsuyama H, Mangindaan R E, Yano T. Protective effect of schizophyllan and scleroglucan against Streptococcus sp. infection in Yellow Tail (Seriola quinqueradiata) [J]. Aquaculture, 1992,101:197-203.
[21]Oh K W, Lee C K, Kim Y S, et al. Antiherpetic activites of acidic protein bound polysaccharide isolated from Ganoderma lucidum alone and in combinations with acyclovir and vidarabine [J]. Journal of Ethnopharmacology,2000,72:221-227.
[22]Tsukagoshi S. Krestin (PSK) [J]. Cancer Treat Review,1984,11:131-55.
[23]Ooi V E C. Pharmacological studies on certain mushroom from China [J]. International Journal of Medicinal Mushrooms,2001,3:341-354.
[24]Lin W H, Hung C H, Hsu C I, et al. Dimerzation of the Nterminal amphipathic α-helix domain of the fungal immunomodulatory protein from Ganoderma tsugae (Fip-gts) defined by a yeast two-hybride system and site-directed mutagenesis [J]. Journal of Biological Chemistry,1997, 272:20044-20048.
[25]E1-Mekkawy S, E1-Mekkawy S, Meselhy M R, et al. Anti-HIV-1 and anti-H1V-1-protease substances from Ganoderma lucidum [J]. Phytochemistry,1998,49:1651-1657.
[26]Chairul, Tokuyama T, Hayashi Y, et al. Applanoxidic acids A, B, C and D, biologically active tetracyclic triterpenes from Ganoderma applanatum [J]. Phytochemistry,1991,30:4105-4109.
[27]Toth J O, Luu B, Ourisson G. Ganoderic acid T and Z:cytotoxic triterpenes from Ganoderma lucidum (Polyporaceae) [J]. Tetrahedron Letters,1983,24:1081-1084.
[28]Kohda H, Tokumoto W, Sakamoto K, et al. The biologically active constituents of Ganoderma lucidum (Fr.) Karst, histamine release-inhibitory triterpenes [J]. Chemical and Pharmaceutical Bulletin,1985,33:1367-1374.
[29]Morigiwa A, Kitabatake K, Fujimoto Y, et al. Angiotensin converting enzyme-inhibitory triterpenes from Ganoderma lucidum [J]. Chemical and Pharmaceutical Bulletin,1986,34:3025-3028.
[30]Lin C N, Tome W P. Novel cytotoxic principle of Formosan Ganoderma lucidum [J]. Journal of Natural Products,1991,54:998-1002.
[31]Bok J W, Lermer L, Chilton J, et al. Antitumor sterols from the mycelia of Cordyceps sinensis [J]. Phytochemistry,1999,51:891-898.
[32]Keller A C, Maillard M P, Hostettmann K. Antimicrobial steroids from the fungus Fomitopsis pinicola [J]. Phytochemistry,1996,41:1041-1046.
[33]Menoli R C R, Mantovani M S, Ribeiro L R, et al. Antimutagenic effects of the mushroom Agaricus blazei Murrill extracts on V79 cells [J]. Mutation Research,2001,496:5-13.
[34]Moradali M F, Mostafavi H, Hedjaroude G A, et al. Investigation of antibacterial potentiality of methanol extraction from fungus Ganoderma applanatum. World Conference on Magic Bullets Celebrating Paul Ehrlich 150th Birthday, Nurnberg, Germany,2004.
[35]Chiu S W,Wang Z M, Leung T M, et al. Nutritional value of Ganoderma extract and assessment of its genotoxicity and antigenotoxicity using comet assay of mouse lymphocytes [J]. Food and Chemical Toxicology,2000,38:173-178.
[36]Shimizu A, Yano T, Saito Y, et al. Isolation of an inhibitor of platelet aggregation from a fungus, Ganoderma lucidum [J]. Chemical and Pharmaceutical Bulletin,1985,33:3012-3015.
[37]Gottlieb D. Viomycin In:Gottlicb D, Shaw P D, eds. Antibiotics I, Mechanism of action [M], Springer-Verlag Berlin; 1967,677-680.
[38]Wasser S P. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides [J]. Applied Microbiology and Biotechnology,2002,60:258-274.
[39]汪建敏,焦阳,吕凤霞,等.食药用真菌翅鳞伞菌丝体蛋白活性的研究[J].江西农业学报,2008,20(8)：99-101.
[40]赵海珍,王娟,吕凤霞,等.翅鳞伞AS5.245胞内粗多糖抗肿瘤作用的研究[J].食品科学,2008,29(12)：678-680.
[41]Chang S T, Miles P G. The nutritional attributes of edible mushrooms [M]. In Mushrooms: Cultivation, Nutritional Value, Medicinal Effect, and Environmental Impact. Boca Raton, FL: CRC Press,2004,27-38.
[42]Kasuga A, Aoyagi Y, Sugahara T. Antioxidative activities of several mushroom extracts [J]. Journal of the Japanese Society for Food Science and Technology,1993,40:56-63.
[43]Mau J L, Chao G R, Wu K T. Antioxidant properties of methanolic extracts from several ear mushrooms [J]. Journal of Agricultural and Food Chemistry,2001,49:5461-5467.
[44]Yang J H, Lin H C, Mau J L. Antioxidant properties of several commercial mushrooms [J]. Food Chemistry,2002,77:229-235.
[45]Mau J L, Lin H C, Song S F. Antioxidant properties of several specialty mushrooms [J]. Food Research International,2002,35:519-526.
[46]Tsai S Y, Huang S J, Mau J L. Antioxidant properties of hot-water extracts from Agrocybe cylindracea [J]. Food Chemistry,2006,98:670-677.
[47]Lee Y L, Yen M T, Mau J L. Antioxidant properties of various extracts from Hypsizigus marmoreus [J]. Food Chemistry,2007,104:1-9.
[48]Lo KM, Cheung PCK. Antioxidant activity of extracts from the fruiting bodies of Agrocybe aegerita var. alba [J]. Food Chemistry,2005,89:533-539.
[49]Elmastas M, Isildak O, Turkekul I, Temur N. Determination of antioxidant activity and antioxidant compounds in wild edible mushrooms [J]. Journal of Food Composition and Analysis,2007,20: 337-345.
[50]Shon M Y, Kim T H, Sung N J. Antioxidants and free radical scavenging activity of Phellinus baumii (Phellinus of Hymenochaetaceae) extracts [J]. Food Chemistry,2003,82:593-597.
[51]Luo J G, Liu J, Sun Y, et al. Medium optimization, preliminary characterization and antioxidant activity in vivo of mycelial polysaccharide from Phellinus baumii Pilat [J]. Carbohydrate Polymers,2010,81:533-540.
[52]Reis FS, Martins A, Barros L, et al. Antioxidant properties and phenolic profile of the most widely appreciated cultivated mushrooms:a comparative study between in vivo and in vitro samples [J]. Food and Chemical Toxicology,2012, doi:10.1016/j.fct.2012.02.013.
[53]Palacios I, Lozano M, Moro C, et al. Antioxidant properties of phenolic compounds occurring in edible mushrooms [J]. Food Chemistry,2011,128:674-678.
[54]Liu Y T, Sun J, Luo Z Y, et al. Chemical composition of five wild edible mushrooms collected from Southwest China and their antihyperglycemic and antioxidant activity [J]. Food and Chemical Toxicology,2012, doi:10.1016/j.fct.2012.01.023.
[55]Ishikawa Y, Marimoto K, Hamasaki T. Flavoglaucin, a metabolite of Eurotium chavalieri, its oxidation and synergism with tocopherol [J]. Journal of the American Oil Chemists'Society, 1984,61:1864-1868.
[56]Tokita F, Shibukawa N, Yasumoto T, et al. Isolation and chemical structure of the plasma-cholesterol reducing substance from Shiitake mushroom [J]. Mushroom Science,1972,8: 783-788.
[57]Suzuki S, Ohshima S. Influence of shiitake (Lentinus edodes) on human serum cholesterol [J]. Mushroom Science,1976,9,463-470.
[58]Bobek P, Ozdin L, Galbavy S. Dose-and time-dependent hypocholesterolemic effect of oyster mushroom(Pleurotus ostreatus) in rats [J]. Nutrition,1998,14:282-286.
[59]Fukushima M, Nakano M, Morii Y, et al. Hepatic LDL receptor mRNA is increased by dietary mushroom (Agaricus bisporus) fiber and sugar beet fiber [J]. Journal of Nutrition,2000,130: 2151-2156.
[60]Ng Y F. In vitro and in vivo antioxidant activity and hypocholesterolemic effect in extracts of Agrocybe aegerita. M.Phil, thesis. Hong Kong:The Chinese University of Hong Kong.2005.
[61]Chen J J, Mao D, Yong Y Y, et al. Hepatoprotective and hypolipidemic effects of water-soluble polysaccharidic extract of Pleurotus eryngii [J]. Food Chemistry,2012,130(3):687-694.
[62]崔莉,董明盛,陈晓红,等.一株纤溶酶产生菌-蛹虫草的形态和分子鉴定[J].江苏农业学报,2010,26(3)：667-669.
[63]Kiho T, Kochi M, Usui S, et al. Antidiabetic effect of an acidic polysaccharide (TAP) from Tremella aurantia Schw.:Fr. (Heterobasidiomycetes) in genetically diabetic KKAy mice [J]. International Journal of Medicinal Mushrooms,2002,4:291-297.
[64]Swanston-Flatt S K, Day C, Flatt P R, et al. Glycemic effects of traditional European plant treatments for diabetes:Studies in normal and streptozotocin diabetic mice [J]. Diabetes Research and Clinical Practice,1989,10:69-73.
[65]Kurushima H, Kodama N, Nanba H. Activities of polysaccharides obtained from Grifola frondosa on insulin-dependent diabetes mellitus induced by streptozotocin in mice [J]. Mycoscience,2000, 41:473-480.
[66]Kiho T, Morimoto H, Kobayashi T, et al. Effect of a polysaccharide (TAP) from the fruiting bodies of Tremella aurantia on glucose metabolism in mouse liver [J]. Bioscience, Biotechnology, and Biochemistry,2000,64:417-419.
[67]Gao Y, Lan J, Dai X, et al. A phase Ⅰ/Ⅱ study of ling zhi mushroom Ganoderma lucidum (W.Curt.:Fr.) Lloyd (Aphyllophoromycetidae) extract in patients with type II diabetes mellitus [J]. International Journal of Medicinal Mushrooms,2004,6:33-39.
[68]Eo S K, Kim Y S, Lee C K, et al. Antiviral activities of various water and methanol soluble substances isolated from Ganoderma lucidum [J]. Journal of Ethnopharmacology,1999,68: 129-136.
[69]Takazawa H, Tajima F, Miyashita C. An antifungal compound from "Shiitake" (Lentinus edodes) [J]. Yakugaku Zasshi,1982,102:489-491.
[70]Mothana R A A, Jansen R, Julich W D, et al. Ganomycin A and B, new antimicrobial farnesyl hydroquinones from the basidiomycete Ganoderma pfeifferi [J]. Journal of Natural Products, 2000,63:416-418.
[71]Badalyan S M. Antiprotozoal activity and mitogenic effect of mycelium of culinary-medicinal shiitake mushroom Lentinus edodes (Berk.) Singer (Agaricomycetidae) [J]. International Journal of Medicinal Mushrooms,2004,6:131-138.
[72]Brandt C R, Piraino F. Mushroom antivirals [J]. Antimicrobial Agents and Chemotherapy\Antimicrob. Agents Chemother,2000,4:11-26.
[73]Mothana R A A, Awadh N A A, Jansen R, et al. Antiviral lanostanoid triterpenes from the fungus Ganoderma pfeifferi Bres [J]. Fitoterapia,2003,74:177-180.
[74]Awadh A A N, Mothana R A A, Lesnau A, et al. Antiviral activity of extracts and compounds from Inonotus hispidus [J]. Fitoterapia,2003,74:483-485.
[75]Sano M, Yoshino K, Matsuzawa T, et al. Inhibitory effects of edible higher basidiomycetes mushroom extracts on mouse type Ⅳ allergy [J]. International Journal of Medicinal Mushrooms, 2002,4:37-41.
[76]Ali N A A, Pilgrim H, Ludke J, et al. Inhibition of chemiluminescence response of human mononuclear cells and suppression of mitogeninduced proliferation of spleen lymphocytes of mice by hispolon and hispidin [J]. Pharmazie,1996,51:667-670.
[77]Chen R Y, Yu D Q. Studies on the triterpenoid constituents of the spores from Ganoderma lucidum Karst [J]. Journal of Pharmaceutical Sciences,1993,2:91-96.
[78]Wang M Y, Liu Q, Che Q M, et al. Effects of total triterpenoids extract from Ganoderma lucidum (Curt.:Fr.) P.Karst. (Reishi Mushroom) on experimental liver injury models induced by carbon tetrachloride or d-galactosamine in mice [J]. International Journal of Medicinal Mushrooms, 2002,4:337-342.
[79]Gao Y, Zhou S, Chen G, et al. A phase Ⅰ/Ⅱ study of a Ganoderma lucidum (Curt.:Fr.) P.Karst. (Ling Zhi, Reishi mushroom) extract in patients with chronic hepatitis B [J]. International Journal of Medicinal Mushrooms,2002,4:2321-2327.
[80]Nada S A, Omara E A, Abdel-Salam O M E, et al. Mushroom insoluble polysaccharides prevent carbon tetrachloride-induced hepatotoxicity in rat [J]. Food and Chemical Toxicology,2010,48: 3184-3188.
[81]Gibson G R, Probert H M, Rastall R A, et al. Dietary modulation of the human colonic microbiota: updating the concept of prebiotics [J]. Nutrition Research Reviews,2004,17:259-275.
[82]Macfarlane S, Macfarlane G T, Cumming J H. Review article:prebiotics in the gastrointestinal tract [J]. Alimentary Pharmacology and Therapeutics,2006,24:701-714.
[83]Douglas L C, Sanders M E. Probiotics and prebiotics in dietetics practice [J]. Journal of the American Dietetic Association,2008,108:510-521.
[84]Wang Y. Prebiotics:present and future in food science and technology [J]. Food Research International,2009,42:8-12.
[85]Vetter J. Chitin content of cultivated mushrooms Agaricus bisporus, Pleurotus ostreatus and Lentinula edodes [J]. Food Chemistry,2007,102:6-9.
[86]Tao Y, Zhang L, Cheung P C K. Physicochemical properties and antitummor activities of water-soluble native and sulfated hyperbranched mushroom polysaccharides [J]. Carbohydrate Research,2006,341:2261-2269.
[87]Van Loo J. Inulin-type fructans as prebiotics. In G. R. Gibson, & R. A. Rastall (Eds.), Prebiotics: Development and application (pp.59). Hoboken, NJ:John Wiley & Sons,2006.
[88]Synytsya A, Mickova K, Synytsya A, et al. Glucans from fruit bodies of cultivated mushrooms Pleurotus ostreatus and Pleurotus eryngii:structure and potential prebiotic activity [J]. Carbohydrate Polymers,2009,76(4):548-556.
[89]Luo J J, Liu J, Ke C L,et al. Optimization of medium composition for the production of exopolysaccharides from Phellinus baumii Pilot in submerged culture and the immuno-stimulating activity of exopolysaccharides [J]. Carbohydrate Polymers,2009,78(3): 409-415.
[90]方庆华,钟建江.灵芝真菌发酵生产灵芝多糖和灵芝酸[J].华东理工大学学报,2001,27(3)： 254-257.
[91]夏志兰,俞挑生,周连玉,等.灵芝液体发酵条件的优化研究[J].微生物学杂志,2007,27(2)：10-15.
[92]邢燕,杨晓彤,杨庆尧,等.灵芝液体深层发酵研究进展[J].工业微生物,2007,37(3)：63-67
[93]刘忠义,曾虹燕.茯苓液体培养研究初探[J].湘潭大学自然科学学报,2002,24(4)：49-51.
[94]王谦,闫蕾蕾,王超.茯苓液体培养条件研究及其营养浓缩液的相关检测[J].食用菌学报,2003,10(2)：17-20.
[95]李羿,万德光,裴瑾.茯苓液体发酵条件的研究[J].成都中医药大学学报,2005,28(1)：52-55.
[96]尚德静,王孝敏.冬虫夏草深层发酵的研究[J].中国食用菌,1996,15(6)：48-49.
[97]钟士清,胡文峰,罗国威.冬虫夏草头孢菌菌丝体液体发酵条件研究[J].华南农业大学学报,1995,16(3)：108-111.
[98]王允祥,陆兆新.翅鳞伞培养条件响应面法优化研究[J].微生物学通报,2004,31(6)：42-47.
[99]Zhao H Z, Wang J, Lu Z X. Optimization of process parameters of the Pholiota squarrosa extracellular polysaccharide by Box-Behnken statistical design [J]. Carbohydrate Polymers,2009, 77 (3):677-680.
[100]刘少琴,赵紫华,马彩霞,等.药用真菌液体发酵培养的研究进展[J].中国现代中药,2006,8(7)：28-31,35.
[101]Ruiz-Herrera J. Fungal cell wall:Structure, synthesis, and assembly [M]. Boca Raton, Ann Arbor, London:CRC press,1956.
[102]Sietsman J H, Wessels J G H. Evidence for covalent linkages between chitin and β-glucan in a fungal wall [J]. Journal of Genetic Microbiology,1979,114,99-105.
[103]Mizuno T, Ohsawa K, Hagiwara N, et al. Fractionation and characterization of antitumor polysaccharides from Maitake, Grifola frondosa [J]. Agricultural Biology and Chemistry,1986, 50:1679-1688.
[104]Mizuno T, Hagiwara T, Nakamura T, et al. Antitumor activity and some properties of water-soluble polysaccharides from "Himematsutake", the fruiting body of Agaricus blazei Murrill [J]. Agricultural Biology and Chemistry,1990,54:2889-2896.
[105]Zhang M, Cui S W, Cheung P C K, et al. Antitumor polysaccharides from mushrooms:a review on their isolation process, structural characteristics and antitumor activity [J]. Trends in Food Science & Technology,2007,18:4-19.
[106]Nauts H C, Swift W E, Coley B L. The treatment of malignant tumors by bacterial toxins as developed by the late William B. Coley, reviewed in the light of modern research [J]. Cancer Research,1946,6:205-214.
[107]Chihara G. The antitumor polysaccharide lentinan:an overview. In T. Aoki, et al. (Eds.), Manipulation of host defense mechanism [J]. Nature,1969,222:687-694.
[108]Ikekawa T. Beneficial effects of edible and medicinal mushrooms in health care [J]. International Journal Medical Mushrooms,2001,3:291-298.
[109]Ooi V E C, Liu F. A review of pharmacological activities of mushroom polysaccharides [J]. International Journal of Medicinal Mushrooms,1999,1:195-206.
[110]Maeda Y Y, Chihara G. Lentinan, a new immunoaccelerator of cells-mediated responses [J]. Nature,1971,229:634-647.
[111]Chihara G. Immunopharmacology of lentinan, a polysaccharide isolated from lentinus edodes:its application as a host defense potentiator [J]. International Journal Oriental Medicine,1992,17: 57-77.
[112]Maeda Y Y, Watanabe S T, Chihara C, et al. Denaturation and renaturation of α β-1,6;1,3-glucan, lentinan, associated with expression of T-cell-mediated responses [J]. Cancer Research,1988,48: 671-675.
[113]Suzuki M, Iwashiro M, Takatsuki F, et al. Reconstitution of antitumor effects of lentinan in nude mice:roles of delayed-type hypersensitivity reaction triggered by CD4-positive T cell clone in the infiltration of effector cells into tumor [J]. Japanese Journal of cancer Research,1994,85: 409-417.
[114]Taki H, Ohishi K, Okano A, et al. Antimetastatic effect of lentinan on liver metastasis of colon carcinoma (Colon 26):possible role of activated Kupffer cells [J]. International Journal of Immunotherapy,1995,11,29-38.
[115]Wang Y Y, Khoo K H, Chen S T, et al. Studies on the immuno-modulating and antitumor activities of Ganoderma lucidum (Reishi) polysaccharides:functional and proteomic analyses of a fucose-containing glycoprotein fraction responsible for the activities [J]. Bioorganic Medical Chemistry,2002,10:1057-1062.
[116]Chen Y Y, Chang H M. Antiproliferative and differentiating effects of polysaccharide fraction from fu-ling (Poria cocos) on human leukemic U937 and HL-60 cells [J]. Food and Chemical Toxicology,2004,42:759-769.
[117]Li G, Kim D, Kim T, et al. Protein-bound polysaccharide from Phellinus linteus induces G2/M phase arrest and apoptosis in SW480 human colon cancer cells [J]. Cancer Letters,2004,216: 175-181.
[118]Lin X, Cai Y, Li Z, et al. Structure determination, apoptosis induction, and telomerase inhibition of CEP-2, a novel lichenin from Cladonia furcata [J]. Biochimica et Biophysica Acta,2003,1622, 99-108.
[119]Chow L, Lo W, Loo C S, et al. Polysaccharide peptide mediates apoptosis by up-regulating p21 gene and and down-regulating cyclin D1 gene [J]. American Journal Chinese Medicine,2003,31: 1-9.
[120]Zhang M, Cheung P C K, Chiu L C M, et al. Cell-cycle arrest and apoptosis induction in human breast carcinoma MCF-7 cells by carboxymethylated β-glucan from the mushroom sclerotia of Pleurotus tuber-regium [J]. Carbohydrate Polymers,2006,66:455-462.
[121]Kawamura M, Kasai H. Delayed cell cycle progression and apoptosis induced by hemicellulase-treated Agaricus blazei [J]. Evidence-Based Complementary and Alternative Medicine,2007,4(1):83-94.
[122]Yeh W C, Dompa J L, Mccarrach M E, et al. FADD:essential for embryo development and signaling from some, but not all, inducer of apoptosis [J]. Science,1998,279:1954-1955.
[123]Enari M, Sakahira H, Yokoyama H, et al. A caspase-activated DNase that degades DNA during apoptosis, and its inhibitor ICAD [J]. Nature,1998,392:43-50.
[124]Xu H S, Wu Y W, Xu S F, et al. Antitumor and immunomodulatory activity of polysaccharides from the roots of Actinidia eriantha [J]. Journal of Ethnopharmacology,2009,125:310-317.
[125]Zheng R, Su J, Dai H, et al. Characterization and immunomodulating activities of polysaccharide from Lentinus edodes [J]. International Immunopharmacology,2005,5:811-820.
[126]冯优,王凤山,张天民,等.多糖类药物的研究进展[J].中国生化药物杂志,2008,2：129-133,139.
[127]张延坤,张东祥.生物活性多糖的抗肿瘤作用及其机制研究进展[J].解放军预防医学杂志,2006,24：382-385.
[128]冯文茹.我国天然抗肿瘤活性成分的研究进展[J].中华医学研究杂志,2007,7(9)：801-803.
[129]陈执中.天然药物抗癌活性成分研究进展[J].中国民族民间医药杂志,2004,70：249-251.
[130]Vandana S, Arvind S N, Kumar J K, et al. Plant-based anticancer molecules:A chemical and biological profile of some important leads [J]. Bioorganic & Medicinal Chemistry,2005,13: 5892-5908.
[131]Ma X, Wang Z. Anticancer drug discovery in the future:an evolutionary perspective [J]. Drug Discovery Today,2009,14:1137-1142.
[132]Vidi J, Sivakami S, Shahani S, et al. Antihyperglycemic dffects of three extracts from Momordica and Charantia [J]. Journal of ethnopharmacology,2003,88:107.
[133]于红,张学成.螺旋藻多糖对HeLa细胞生长的影响[J].中国海洋药物,2003,22：26.
[134]Yang L, Zhang L. Chemical structural and chain conformational characterization of some bioactive polysaccharides isolated from natural sources [J]. Carbohydrate Polymers,2009,76:349-361.
[135]Bi Z S, Li TH, Zheng G Y, et al. Four new species of Agariacales [J]. Acta Mycologica Sinica, 1985,4:155-161.
[136]Kirk P M, Cannon PF, Minter DW, et al. Dictionary of the Fungi. (10th ed.) [M]. Wallingford: CABI.2008.
[137]Cui Y J, Li Q Z. Immune effect of Pholiota nameko polysaccharide on the aging model mice in the different period [J]. Journal of Northeast Agricultural University,2004,35(2):159-161.
[138]Li H, Lu X, Zhang S, et al. Anti-inflammatory activity of polysaccharide from Pholiota nameko [J]. Biochemistry (Mosc),2008,73:669-675.
[139]Li H, Wang S. Kinetics of inhibition of ribonuclease A by Pholiota Nameko polysaccharide [J]. International Journal of Biological Macromolecules,2007,40:134-138.
[140]Li H, Zhang M, Ma G. Hypolipidemic effect of the polysaccharide from Pholiota nameko [J]. Nutrition,2010,26:556-562.
[141]Zhao H, Wang J, Lu Z. Optimization of process parameters of the Pholiota squarrosa extracellular polysaccharide by Box-Behnken statistical design [J]. Carbohydrate Polymers,2009,77, 677-680.
[142]Zou S, Zhang X, Yao W, et al. Structure characterization and hypoglycemic activity of a polysaccharide isolated from the fruit of Lycium barbarum L [J]. Carbohydrate Polymers,2010, 80:1161-1167.
[143]Jiang C, Wang M, Liu J, et al. Extraction, preliminary characterization, antioxidant and anticancer activities in vitro of polysaccharides from Cyclina sinensis [J]. Carbohydrate Polymers,2011, 84(3):851-857.
[144]Gan D, Ma L, Jiang C, et al. Production, preliminary characterization and antitumor activity in vitro of polysaccharides from the mycelium of Pholiota dinghuensis Bi [J]. Carbohydrate Polymers,2011,84(3):997-1003.
[1]Wasser S P. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides [J]. Applied Microbiology and Biotechnology,2002,60:258-274.
[2]Zaidman BZ, Yassin M, Mahajna J, et al. Medicinal mushroom modulators of molecular targets as cancer therapeutics [J]. Applied Microbiology and Biotechnology,2005,67(4):453-468.
[3]Chen W, Zhao Z, Chen, S F, et al. Optimization for the production of exopolysaccharide from Fomes fomentarius in submerged culture and its antitumor effect in vitro [J]. Bioresource Technology, 2008,99:3187-3194.
[4]Luo J, Liu J, Sun Y, et al. Optimization of Medium optimization, preliminary characterization and antioxidant activity in vivo of mycelial polysaccharide from Phellinus baumii Pilat [J]. Carbohydrate Polymers,2010,81:533-540.
[5]Moradali M F, Mostafavi H, Ghods S, et al. Immunomodulating and anticancer agents in the realm of macromycetes fungi (macrofungi) [J]. International Immunopharmacology,2007,7:701-724.
[6]Peng Y, Zhang L, Zeng F, et al. Structure and antitumor activities of the water-soluble polysaccharides from Ganoderma tsugae mycelium [J]. Carbohydrate Polymers,2005,59: 385-392.
[7]Zhang M, Cui S W, Cheung P C K, et al. Antitumor polysaccharides from mushrooms:a review on their isolation process, structural characteristics and antitumor activity [J]. Trends in Food Science and Technology,2007,18:4-19.
[8]Zhao L, Dong Y, Chen G, et al. Extraction, purification, characterization and antitumor activity of polysaccharides from Ganoderma lucidum [J]. Carbohydrate Polymers,2010,80:783-789.
[9]Cui Y J, Li Q Z. Immune effect of Pholiota nameko polysaccharide on the aging model mice in the different period [J]. Journal of Northeast Agricultural University,2004,35(2):159-161.
[10]Li H, Lu X, Zhang S, et al. Anti-inflammatory activity of polysaccharide from Pholiota nameko [J]. Biochemistry (Mosc),2008,73:669-675.
[11]Li H, Wang S. Kinetics of inhibition of ribonuclease A by Pholiota Nameko polysaccharide [J]. International Journal of Biological Macromolecules,2007,40:134-138.
[12]Li H, Zhang M, Ma G. Hypolipidemic effect of the polysaccharide from Pholiota nameko [J]. Nutrition,2010,26:556-562.
[13]Bi Z S, Li T H, Zheng G Y, et al. Four new species of Agariacales. Acta Mycologica Sinica [J],1985, 4:155-161.
[14]Kirk P M, Cannon P F, Minter D W, et al. Dictionary of the Fungi. (10th ed.) [M]. Wallingford: CABI.2008.
[15]Wasser S P. Current findings, future trends, and unsolved problems in studies of medicinal mushrooms [J]. Applied Microbiology and Biotechnology,2011,89(5):1323-1332.
[16]Cheung P C K. Dietary fiber content and composition of some cultivated edible mushroom fruiting bodies and mycelia [J]. Journal of Agricultural and Food Chemistry 1996,44:468-471.
[17]Aida F M N A, Shuhaimi M, Yazid M, et al. Mushroom as a potential source of prebiotics:a review [J]. Trends in Food Science and Technology,2009,20(11-12):567-575.
[18]Ho Y C, Norli I, Alkarkhi A, et al. Characterization of biopolymeric flocculant (pectin) and organic synthetic flocculant (PAM):A comparative study on treatment and optimization in kaolin suspension [J]. Bioresource Technology,2010,101(4):1166-1174.
[19]Francis F, Sabu A, Nampoothiri K. Use of response surface methodology for optimizing process parameters for the production of a-amylase by Aspergillus oryzae [J]. Biochemical Engineering Journal,2003,15(2):107-15.
[20]Liu C, Liu Y, Liao W, et al. Application of statistically based experimental designs for the optimization of nisin production from whey [J]. Biotechnology Letters,2003,25(11):877-82.
[21]Kshirsagar A C, Singhal R S. Optimization of starch oleate derivatives from native corn and hydrolyzed corn starch by response surface methodology [J]. Carbohydrate Polymers,2007,69: 455-461.
[22]Liu J, Luo J, Ye H, et al. Medium optimization and structural characterization of exopolysaccharides from endophytic bacterium Paenibacillus polymyxa EJS-3 [J]. Carbohydrate Polymers,2010,79: 206-213.
[23]Liu J, Luo J, Ye H, et al. Production, characterization and antioxidant activities in vitro of exopolysaccharides from endophytic bacterium Paenibacillus polymyxa EJS-3 [J]. Carbohydrate Polymers,2009,78:275-281.
[24]Pokhrel C P, Ohga S. Submerged culture conditions for mycelial yield and polysaccharides production by Lyophyllum decastes [J]. Food Chemistry,2007,105:641-646.
[25]Bae J T, Sinha J, Park J P, et al. Optimization of submerged culture conditions for exo-biopolymer production by Paecilomyces japonica [J]. Journal of Microbiology and Biotechnology,2000,10: 482-497.
[26]Kim H O, Lim J M, Joo S W, et al. Optimization of submerged culture condition for the production of mycelial biomass and exopolysaccharide by Agrocybe cylindracea [J]. Bioresource Technology, 2005,96:1175-1182.
[27]Gan D, Ma L P, Jiang C X, et al. Production, preliminary characterization and antitumor activity in vitro of polysaccharides from the mycelium of Pholiota dinghuensis Bi. Carbohydrate Polymers 2011,84:997-1003
[28]王允祥,陆兆新.翅鳞伞培养条件响应面法优化研究[J].微生物学通报,2004,31(6)：42-47.
[29]Zhao H Z, Wang J, Lu Z X. Optimization of process parameters of the Pholiota squarrosa extracellular polysaccharide by Box-Behnken statistical design. Carbohydrate Polymers,2009,77 (3):677-680.
[1]Wasser S P. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides [J]. Applied Microbiology and Biotechnology,2002,60(3):258-274
[2]Zaidman B Z, Yassin M, Mahajna J, et al. Medicinal mushroom modulators of molecular targets as cancer therapeutics [J]. Applied Microbiology and Biotechnology,2005,67(4):453-468
[3]Wasser S P. Current findings, future trends, and unsolved problems in studies of medicinal mushrooms [J]. Applied Microbiology and Biotechnology,2011,89(5):1323-1332
[4]Aida F M N A, Shuhaimi M, Yazid M, et al. Mushroom as a potential source of prebiotics:a review [J]. Trends in Food Science & Technology,2009,20(11-12):567-575
[5]Nada S A, Omara E A, Abdel-Salam O M E, et al. Mushroom insoluble polysaccharides prevent carbon tetrachloride-induced hepatotoxicity in rat [J]. Food and Chemical Toxicology,2010, 48(11):3184-3188
[6]Kozarski M, Klaus A, Niksic M, et al. Antioxidative and immunomodulating activities of polysaccharide extracts of the medicinal mushrooms Agaricus bisporus, Agaricus brasiliensis, Ganoderma lucidum and Phellinus linteus [J]. Food Chemistry,2011,129(4):1667-1675
[7]Gan D, Ma L P, Jiang C X, et al. Production, preliminary characterization and antitumor activity in vitro of polysaccharides from the mycelium of Pholiota dinghuensis Bi [J]. Carbohydrate Polymers,2011,84(3):997-1003
[8]Mahajna J, Dotan N, Zaidman B Z, et al. Pharmacological Values of Medicinal Mushrooms for Prostate Cancer Therapy:The Case of Ganoderma Lucidum [J]. Nutrition and Cancer-an International Journal,2009,61(1):16-26
[9]Zhang M, Cui S W, Cheung P C K, et al. Polysaccharides from mushrooms:a review on their isolation process, structural characteristics and antitumor activity [J]. Trends in Food Science & Technology,2006,18(1):4-19
[10]Vaz J A, Barros L, Martins A, et al. Chemical composition of wild edible mushrooms and antioxidant properties of their water soluble polysaccharidic and ethanolic fractions [J]. Food Chemistry,2011,126(2):610-616
[11]Dubois M, Gilles K A, Hamilton J K, et al. Colorimetric method for determination of sugars and related substances [J]. Analytical Chemistry,1956,28,350-356.
[12]Blumenkrantz M, Asboe-Hansen G. New method for quantitative determination of uronic acids [J]. Analytical Biochemistry,1973,54,484-489.
[13]Bradford M M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding [J]. Analytical Biochemistry,1976,72,248-254.
[14]Kawai Y, Seno N, Anno K. A modified method for chondrosulfatase assay [J]. Analytical Biochemistry,1969,32,314-321.
[15]Liu J, Luo J G, Ye H, et al. Production, characterization and antioxidant activities in vitro of exopolysaccharides from endophytic bacterium Paenibacillus polymyxa EJS-3 [J]. Carbohydrate Polymers,2009,78(2):275-281
[16]Qiao D, Hu B, Gan D, et al. Extraction optimized by using response surface methodology, purification and preliminary characterization of polysaccharides from Hyriopsis cumingii [J]. Carbohydrate Polymers,2009,76(3):422-429
[17]Maciel J S, Chaves L S, Souza B W S, et al. Structural characterization of cold extracted fraction of soluble sulfated polysaccharide from red seaweed Gracilaria birdiae [J]. Carbohydrate Polymers, 2008,71(4):559-565
[18]Peng Y F, Zhang L N, Zeng F B, et al. Structure and antitumor activities of the water-soluble polysaccharides from Ganoderma tsugae mycelium [J]. Carbohydrate Polymers,2005,59(3): 385-392
[19]Liu C H, Li X D, Li Y H, et al. Structural characterisation and antimutagenic activity of a novel polysaccharide isolated from Sepiella maindroni ink [J]. Food Chemistry,2008,110(4):807-813
[20]Zou S, Zhang X, Yao W B, et al. Structure characterization and hypoglycemic activity of a polysaccharide isolated from the fruit of Lycium barbarum L. [J]. Carbohydrate Polymers,2010, 80(4):1161-1167
[21]Yang L Q, Fu S S, Zhu X N, et al. Hyperbranched acidic polysaccharide from green tea [J]. Biomacromolecules,2010,11(12):3395-3405
[1]Hwang Y P, Choi J H, Jeong H G. Protective effect of the Aralia continentalis root extract against carbon tetrachloride-induced hepatotoxicity in mice [J]. Food and Chemical Toxicology, 2009,47(1):75-81
[2]Hsu Y W, Tsai C F, Chang W H, et al. Protective effects of Dunaliella salina-A carotenoids-rich alga, against carbon tetrachloride-induced hepatotoxicity in mice [J]. Food and Chemical Toxicology,2008,46(10):3311-3317
[3]Siegel R, Ward E, Brawley O, et al. Cancer statistics,2011:the impact of eliminating socioeconomic and racial disparities on premature cancer deaths [J]. CA Cancer J Clin,2011, 61(4):212-236
[4]Finkel T, Holbrook N J. Oxidants, oxidative stress and the biology of ageing [J]. Nature,2000, 408(6809):239-247
[5]Valko M, Leibfritz D, Moncol J, et al. Free radicals and antioxidants in normal physiological functions and human disease [J]. International Journal of Biochemistry & Cell Biology,2007, 39(1):44-84
[6]Sun J, Chu Y F, Wu X Z, et al. Antioxidant and anti proliferative activities of common fruits [J]. Journal of Agricultural and Food Chemistry,2002,50(25):7449-7454
[7]Aida F M N A, Shuhaimi M, Yazid M, et al. Mushroom as a,potential source of prebiotics:a review [J]. Trends in Food Science & Technology,2009,20(11-12):567-575
[8]Yoon H, Liu R H. Effect of selected phytochemicals and apple extracts on NF-kappa B activation in human breast cancer MCF-7 cells [J]. Journal of Agricultural and Food Chemistry, 2007,55(8):3167-3173
[9]Eberhardt M V, Lee C Y, Liu R H. Nutrition-Antioxidant activity of fresh apples [J]. Nature, 2000,405(6789):903-904
[10]Wasser S P. Current findings, future trends, and unsolved problems in studies of medicinal mushrooms [J]. Applied Microbiology and Biotechnology,2011,89(5):1323-1332
[11]Zhang M, Cui S W, Cheung P C K, et al. Polysaccharides from mushrooms:a review on their isolation process, structural characteristics and antitumor activity [J]. Trends in Food Science & Technology,2006,18(1):4-19
[12]Ke C, Sun L, Qiao D, et al. Antioxidant acitivity of low molecular weight hyaluronic acid [J]. Food and Chemical Toxicology,2011,49(10):2670-2675
[13]Qiao D, Ke C, Hu B, et al. Antioxidant activities of polysaccharides from Hyriopsis cumingii [J]. Carbohydrate Polymers,2009,78(2):199-204
[14]Luo J, Liu J, Sun Y, et al. Medium optimization, preliminary characterization and antioxidant activity in vivo of mycelial polysaccharide from Phellinus baumii Pilat [J]. Carbohydrate Polymers,2010,81(3):533-540
[15]Ye H, Wang K, Zhou C, et al. Purification, antitumor and antioxidant activities in vitro of polysaccharides from the brown seaweed Sargassum pallidum [J]. Food Chemistry,2008,111(2): 428-432
[16]Gan D, Ma L, Jiang C, et al. Production, preliminary characterization and antitumor activity in vitro of polysaccharides from the mycelium of Pholiota dinghuensis Bi [J]. Carbohydrate Polymers,2011,84(3):997-1003
[17]Fan G J, Tang J J, Bhadauria M, et al. Resveratrol ameliorates carbon tetrachloride-induced acute liver injury in mice [J]. Environmental Toxicology and Pharmacology,2009,28(3): 350-356
[18]Hsu Y W, Tsai C F, Chen W K, et al. Protective effects of seabuckthom(Hippophae rhamnoides L.) seed oil against carbon tetrachloride-induced hepatotoxicity in mice [J]. Food and Chemical Toxicology,2009,47(9):2281-2288
[19]Zaidman B Z, Yassin M, Mahajna J, et al. Medicinal mushroom modulators of molecular targets as cancer therapeutics [J]. Applied Microbiology and Biotechnology,2005,67(4):453-468
[20]Kozarski M, Klaus A, Niksic M, et al. Antioxidative and immunomodulating activities of polysaccharide extracts of the medicinal mushrooms Agaricus bisporus,Agaricus brasiliensis, Ganoderma lucidum and Phellinus linteus [J]. Food Chemistry,2011,129(4):1667-1675
[21]Chen J J, Mao D, Yong Y Y, et al. Hepatoprotective and. hypolipidemic effects of water-soluble polysaccharidic extract of Pleurotus eryngii [J]. Food Chemistry,2012,130(3):687-694
[22]Dhanasekaran M, Ignacimuthu S, Agastian P. Potential hepatoprotective activity of ononitol monohydrate isolated from Cassia tora L. on carbon tetrachloride induced hepatotoxicity in wistar rats [J]. Phytomedicine,2009,16(9):891-895
[23]Miesel R, Sanocka D, Kurpisz M, et al. Antiinflammatory effects of nadph oxidase-inhibitors [J]. Inflammation,1995,19(3):347-362
[24]Nada S A, Omara E A, Abdel-Salam O M E, et al. Mushroom insoluble polysaccharides prevent carbon tetrachloride-induced hepatotoxicity in rat [J]. Food and Chemical Toxicology,2010, 48(11):3184-3188
[25]Tsai C F, Hsu Y W, Chen W K, et al. Hepatoprotective effect of electrolyzed reduced water against carbon tetrachloride-induced liver damage in mice [J]. Food and Chemical Toxicology, 2009,47(8):2031-2036
[26]Shim J Y, Kim M H, Kim H D, et al. Protective action of the immunomodulator ginsan against carbon tetrachloride-induced liver injury via control of oxidative stress and the inflammatory response [J]. Toxicology and Applied Pharmacology,2010,242(3):318-325
[27]Park C M, Youn H J, Chang H K, et al. TOP1 and 2, polysaccharides from Taraxacum officinale, attenuate CC14-induced hepatic damage through the modulation of NF-kappa B and its regulatory mediators [J]. Food and Chemical Toxicology,2010,48(5):1255-1261
[28]Singh N, Kamath V, Narasimhamurthy K, et al. Protective effect of potato peel extract against carbon tetrachloride-induced liver injury in rats [J]. Environmental Toxicology and Pharmacology,2008,26(2):241-246
[1]Siegel R, Ward E, Brawley O, et al. Cancer statistics,2011:the impact of eliminating socioeconomic and racial disparities on premature cancer deaths [J]. CA-A Cancer Journal for Clinicians,2011, 61(4):212-236.
[2]World Health Organization. An update of the global burden of disease in 2004. Geneva, World Health Organization (forthcoming),2004.
[3]World Health Organization. World health statistics 2008. Geneva, World Health Organization,2009.
[4]Chabner B A, Roberts T G. Timeline-chemotherapy and the war on cancer [J]. Nature Reviews Cancer,2005,5:65-72
[5]Sawyers C. Targeted cancer therapy [J]. Nature,2004,432:294-297.
[6]冯文茹.我国天然抗肿瘤活性成分的研究进展[J].中华医学研究杂志,2007,7(9)：801-803.
[7]陈执中.天然药物抗癌活性成分研究进展[J].中国民族民间医药杂志,2004,70：249-251.
[8]Vandana S, Negi A, Kumar J, et al. Plant-based anticancer molecules:A chemical and biological profile of some important leads [J]. Bioorganic & Medicinal Chemistry,2005,13:5892-5908.
[9]Ma X, Wang Z. Anticancer drug discovery in the future:an evolutionary perspective [J]. Drug Discovery Today,2009,14:1137-1142.
[10]Yeh W, Dompa J, Mccarrach M, et al. FADD:essential for embryo development and signaling from some, but not all, inducer of apoptosis [J]. Science,1998,279,1954-1955.
[11]Enari M, Sakahira H, Yokoyama H, et al. A caspase-activated DNase that degades DNA during apoptosis, and its inhibitor ICAD [J]. Nature,1998,392,43-50.
[12]Xu H, WuY, Xu S, et al. Antitumor and immunomodulatory activity of polysaccharides from the roots of Actinidia eriantha [J]. Journal of Ethnopharmacology,2009,125,310-317.
[13]Ruan Z, Su J, Dai H, et al. Characterization and immunomodulating activities of polysaccharide from Lentinus edodes [J]. International Immunopharmacology,2005,5,811-820.
[14]冯优,王凤山,张天民,等.多糖类药物的研究进展[J].中国生化药物杂志,2008,2,129-133,139.
[15]张延坤,张东祥.生物活性多糖的抗肿瘤作用及其机制研究进展[J].解放军预防医学杂志,2006,24,382-385.
[16]Vidi J, Sivakami S, Shahani S, et al. Antihyperglycemic dffects of three extracts from Momordica and charantia [J]. Journal of ethnopharmacology,2003,88,107.
[17]于红,张学成.螺旋藻多糖对HeLa细胞生长的影响[J].中国海洋药物,2003,22,26.
[18]Yang L, Zhang L. Chemical structural and chain conformational characterization of some bioactive polysaccharides isolated from natural sources [J]. Carbohydrate Polymers,2009,76,349-361.
[19]Mosmann T. Rapid colorimetric assay for cellular growth and survival:Application to proliferation and cytotoxicity assays [J]. Journal of Immunological Methods,1983,65(1-2),55-63.
[20]Felice D L, Sun J, Liu R H. A modified methylene blue assay for accurate cell counting [J]. Journal of Functional Foods,2009,1(1):109-118
[21]Yoon H, Liu R H. Effect of 2alpha-hydroxyursolic acid on NF-kB activation induced by TNF-alpha in human breast cancer MCF-7 cells [J]. Journal of Agriculture and Food Chemistry,2008,56(18): 8412-8417.
[22]Adams L S, Phung S, Yee N, et al. Blueberry Phytochemicals Inhibit Growth and Metastatic Potential of MDA-MB-231 Breast Cancer Cells through Modulation of the Phosphatidylinositol 3-Kinase Pathway [J]. Cancer Research,2010,70(9):3594-3605.
[23]Yoon H, Liu R H. Effect of selected phytochemicals and apple extracts on NF-kappaB activation in human breast cancer MCF-7 cells [J]. Journal of Agriculture and Food Chemistry,2007,55(8): 3167-3173.
[24]Liu R H, Jacob J, Tennant B. Chemiluminescent detection of protein molecular weight markers in Western blot techniques [J]. Biotechniques,1997,22(4):594-595.
[19]Mosmann T. Rapid colorimetric assay for cellular growth and survival:Application to proliferation and cytotoxicity assays. Journal of Immunological Methods,1983,65(1-2),55-63.
[20]Felice D L, Sun J, Liu R H. A modified methylene blue assay for accurate cell counting [J]. Journal of Functional Foods,2009,1(1):109-118
[21]Yoon H, Liu R H. Effect of 2a-hydroxyursolic acid on NF-kB activation induced by TNF-a in human breast cancer MCF-7 cells [J]. Journal of Agriculture and Food Chemistry,2008,56(18): 8412-8417.
[22]Adams L S, Phung S, Yee N, et al. Blueberry Phytochemicals Inhibit Growth and Metastatic Potential of MDA-MB-231 Breast Cancer Cells through Modulation of the Phosphatidylinositol 3-Kinase Pathway [J]. Cancer Research,2010,70(9):3594-3605.
[23]Yoon H, Liu R H. Effect of selected phytochemicals and apple extracts on NF-kB activation in human breast cancer MCF-7 cells [J]. Journal of Agriculture and Food Chemistry,2007,55(8): 3167-3173.
[24]Liu R H, Jacob J, Tennant B. Chemiluminescent detection of protein molecular weight markers in Western blot techniques [J]. Biotechniques,1997,22(4):594-595.
[25]Daba A, Ezeronye O. Anti-cancer effect of polysaccharides isolated from higher basidiomycetes mushrooms [J]. African Journal of Biotechnology,2003,2(12):672-678.
[26]Frantz G. Polysaccharides in pharmacy:Current applications and future concepts [J]. Planta Medicine,1989,55:493-497.
[27]Wasser S P. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides [J]. Applied Microbiology and Biotechnology,2002,60:258-274.
[28]Zaidman B, Yassin M, Mahajna J, et al. Medicinal mushroom modulators of molecular targets as cancer therapeutics [J]. Applied Microbiology and Biotechnology,2005,67:453-468.
[29]Lee B, Bae J, Pyo H, et al. Biological activities of the polysaccharides produced from submerged culture of the edible basidiomycete Grifola frondosa [J]. Enzyme and Microbial Technology,2003, 32:574-581.
[30]Song G, Du Q. Isolation of a polysaccharide with anticancer activity from Auricularia polytricha using high-speed countercurrent chromatography with an aqueous two-phase system [J]. Journal of Chromatography A,2010,1217:5930-5934.
[31]Cui F, Tao W, Xu Z, et al. Structural analysis of antitumor heteropolysaccharide GFPSlb from the cultured mycelia of Grifola frondosa GF9801 [J]. Bioresource Technology,2007,98:395-401.
[32]Jin Y, Zhang L, Zhang M, et al. Antitumor activities of heteropolysaccharides of Poria cocos mycelia from different strains and culture media [J]. Carbohydrate Research,2003,338: 1517-1521.
[33]Li G, Kim D, Kim T, et al. Protein-bound polysaccharide from Phellinus linteus induces G2/M phase arrest and apoptosis in SW480 human colon cancer cells [J]. Cancer Letters,2004,216: 175-181.
[34]Zhang M, Cui S W, Cheung P C K, et al. Antitumor polysaccharides from mushrooms:a review on their isolation process, structural characteristics and antitumor activity [J]. Trends in Food Science & Technology,2007,18:4-19.
[35]Zou S, Zhang X, Yao W, et al. Structure characterization and hypoglycemic activity of a polysaccharide isolated from the fruit of Lycium barbarum L [J]. Carbohydrate Polymers,2010, 80:1161-1167.
[36]Wasser S P. Current findings, future trends, and unsolved problems in studies of medicinal mushrooms [J]. Applied Microbiology and Biotechnology,2011,89(5):1323-1332
[37]Soule H D, Maloney T M, Wolman S R, et al. Isolation and Characterization of a Spontaneously Immortalized Human Breast Epithelial-Cell Line, Mcf-10 [J]. Cancer Research,1990,50(18): 6075-6086.
[38]Sun J, Liu R H. Cranberry phytochemical extracts induce cell cycle arrest and apoptosis in human MCF-7 breast cancer cells [J]. Cancer Letters,2006,241(1):124-134.
[39]Sommers C L, Walkerjones D, Heckford S E, et al. Vimentin Rather Than Keratin Expression in Some Hormone-Independent Breast-Cancer Cell-Lines and in Oncogene-Transformed Mammary Epithelial-Cells [J]. Cancer Research,1989,49(15):4258-4263.
[40]Wasser S P. Medicinal mushrooms:ancient traditions, contemporary knowledge, and scientific enquiries [J]. International Journal for Medicinal Mushrooms,2007,9(3/4):187-189.
[41]Wasser S P. Medicinal mushroom science:history, current Status, future trends, and unsolved problems [J]. International Journal of Medicinal Mushrooms,2010,12(1):1-16.
[42]Hiyama H, Iavarone A, Reeves S A. Regulation of the cdk inhibitor p21 gene during cell cycle progression is under the control of the transcription factor E2F [J]. Oncogene,1998,16(12): 1513-1523
[43]Morris M C, Divita G. Characterization of the interactions between human cdc25C, cdks, cyclins and cdk-cyclin complexes [J]. Journal of Molecular Biology,1999,286(2):475-487
[44]Sun J, Liu R H. Cranberry phytochemical extracts induce cell cycle arrest and apoptosis in human MCF-7 breast cancer cells [J]. Cancer Letters,2006,241(1):124-134.
[45]Prakobwong S, Gupta S C, Kim J H, et al. Curcumin suppresses proliferation and induces apoptosis in human biliary cancer cells through modulation of multiple cell signaling pathways [J]. Carcinogenesis, 2011,32(9):1372-1380.
[46]Kim S P, Kang M Y, Choi Y H, et al. Mechanism of Hericium erinaceus (Yamabushitake) mushroom-induced apoptosis of U937 human monocytic leukemia cells [J]. Food & Function,2011, 2(6):348-356.
[1]Siegel R, Ward E, Brawley O, et al. Cancer statistics,2011:the impact of eliminating socioeconomic and racial disparities on premature cancer deaths [J]. CA Cancer J Clin,2011, 61(4):212-236
[2]Desantis C, Siegel R, Bandi P, et al. Breast cancer statistics,2011 [J]. CA Cancer J Clin,2011:
[3]Adams L S, Phung S, Yee N, et al. Blueberry phytochemicals inhibit growth and metastatic potential of MDA-MB-231 breast cancer cells through modulation of the phosphatidylinositol 3-Kinase pathway [J]. Cancer Research,2010,70(9):3594-3605
[4]Ray R B, Raychoudhuri A, Steele R, et al. Bitter melon (Momordica charantia) extract inhibits breast cancer cell proliferation by modulating cell cycle regulatory genes and promotes apoptosis [J]. Cancer Research,2010,70(5):1925-1931
[5]Prakobwong S, Gupta S C, Kim J H, et al. Curcumin suppresses proliferation and induces apoptosis in human biliary cancer cells through modulation of multiple cell signaling pathways [J]. Carcinogenesis,2011,32(9):1372-1380
[6]Eberhardt M V, Lee C Y, Liu R H. Nutrition-Antioxidant activity of fresh apples [J]. Nature, 2000,405(6789):903-904
[7]Chu Y F, Sun J, Wu X Z, et al. Antioxidant and anti proliferative activities of common vegetables [J]. Journal of Agricultural and Food Chemistry,2002,50(23):6910-6916
[8]Sun J, Chu Y F, Wu X Z, et al. Antioxidant and anti proliferative activities of common fruits [J]. Journal of Agricultural and Food Chemistry,2002,50(25):7449-7454
[9]Gan D, Ma L P, Jiang C X, et al. Production, preliminary characterization and antitumor activity in vitro of polysaccharides from the mycelium of Pholiota dinghuensis Bi [J]. Carbohydrate Polymers,2011,84(3):997-1003
[10]Wolfe K, Wu X Z, Liu R H. Antioxidant activity of apple peels [J]. Journal of Agricultural and Food Chemistry,2003,51(3):609-614
[11]Sun J, Liu R H. Cranberry phytochemical extracts induce cell cycle arrest and apoptosis in human MCF-7 breast cancer cells [J]. Cancer Letters,2006,241(1):124-134
[12]Liu J R, Dong H W, Chen B Q, et al. Fresh Apples suppress mammary carcinogenesis and proliferative activity and induce apoptosis in mammary tumors of the sprague-dawley rat [J]. Journal of Agricultural and Food Chemistry,2009,57(1):297-304
[13]Sliva D. Medicinal mushroom Phellinus linteus as an alternative cancer therapy (Review) [J]. Experimental and Therapeutic Medicine,2010,1(3):407-411
[14]Wasser S P. Medicinal mushroom science:history, current status, future trends, and unsolved problems [J]. International Journal of Medicinal Mushrooms,2010,12(1):1-16
[15]Luo J, Liu J, Sun Y, et al. Medium optimization, preliminary characterization and antioxidant activity in vivo of mycelial polysaccharide from Phellinus baumii Pilat [J]. Carbohydrate Polymers,2010,81(3):533-540
[16]Aida F M N A, Shuhaimi M, Yazid M, et al. Mushroom as a potential source of prebiotics:a review [J]. Trends in Food Science & Technology,2009,20(11-12):567-575
[17]Bera A K, Rana T R, T., Das S, et al. Mushroom lectin protects arsenic induced apoptosis in hepatocytes of rodents [J]. Human & Experimental Toxicology,2011,30(4):307-317
[18]Balogh G, Soares R, Meireles M, et al. Maitake (D fraction) mushroom extract induces apoptosis in breast cancer cells by BAK-1 gene activation [J]. Journal of Medicinal Food,2011, 14(6):563-572
[19]Mahajna J, Dotan N, Zaidman B Z, et al. Pharmacological values of medicinal mushrooms for prostate cancer therapy:the case of Ganoderma Lucidum [J]. Nutrition and Cancer-an International Journal,2009,61(1):16-26
[20]Chow L W C, Lo C S Y, Loo W T Y, et al. Polysaccharide peptide mediates apoptosis by up-regulating p21 gene and down-regulating cyclin D1 gene [J]. American Journal of Chinese Medicine,2003,31(1):1-9
[21]Zhang M, Chiu L C M, Cheung P C K, et al. Growth-inhibitory effects of a (3-glucan from the mycelium of Poria cocos on human breast carcinoma MCF-7 cells:Cell-cycle arrest and apoptosis induction [J]. Oncology Reports,2006,15(3):637-643
[22]Kim S P, Kang M Y, Kim J H, et al. Composition and mechanism of antitumor effects of Hericium erinaceus mushroom extracts in tumor-bearing mice [J]. Journal of Agricultural and Food Chemistry,2011,59(18):9861-9869
[23]Wasser S P. Current findings, future trends, and unsolved problems in studies of medicinal mushrooms [J]. Applied Microbiology and Biotechnology,2011,89(5):1323-1332
[24]Yoon H, Liu R H. Effect of selected phytochemicals and apple extracts on NF-kB activation in human breast cancer MCF-7 cells [J]. Journal of Agricultural and Food Chemistry,2007,55(8): 3167-3173
[25]Yoon H, Liu R H. Effect of 2 a-hydroxyursolic acid on NF-kB activation induced by TNF-a in human breast cancer MCF-7 cells [J]. Journal of Agricultural and Food Chemistry,2008,56(18): 8412-8417
[26]Liu R H, Jacob J, Tennant B. Chemiluminescent detection of protein molecular weight markers in Western blot techniques [J]. Biotechniques,1997,22(4):594-595
[27]Kawamura M, Kasai H. Delayed cell cycle progression and apoptosis induced by hemicellulase-treated Agaricus blazei [J]. Evidence-Based Complementary and Alternative Medicine,2007,4(1):83-94
[28]Huang G J, Deng J S, Huang S S, et al. Hispolon induces apoptosis and cell cycle arrest of human hepatocellular carcinoma Hep3B cells by modulating ERK phosphorylation [J]. Journal of Agricultural and Food Chemistry,2011,59(13):7104-7113
[29]Kim S P, Kang M Y, Choi Y H, et al. Mechanism of Hericium erinaceus (Yamabushitake) mushroom-induced apoptosis of U937 human monocytic leukemia cells [J]. Food & Function, 2011,2(6):348-356
[30]Hattori T S, Komatsu N, Shichijo S, et al. Protein-bound polysaccharide K induced apoptosis of the human Burkitt lymphoma cell line, Namalwa [J]. Biomedicine & Pharmacotherapy,2004, 58(4):226-230
[31]Kono K, Kawaguchi Y, Mizukami Y, et al. Protein-bound polysaccharide K partially prevents apoptosis of circulating T cells induced by anti-cancer drug S-l in patients with gastric cancer [J]. Oncology,2008,74(3-4):143-149
[32]Zhang M, Cui S W, Cheung P C K, et al. Polysaccharides from mushrooms:a review on their isolation process, structural characteristics and antitumor activity [J]. Trends in Food Science & Technology,2006,18(1):4-19
[33]Elmore S. Apoptosis:A review of programmed cell death [J]. Toxicologic Pathology,2007, 35(4):495-516
[34]Chipuk J E, Kuwana T, Bouchier-Hayes L, et al. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis [J]. Science,2004,303(5660): 1010-1014
[35]Buckley C D, Pilling D, Henriquez N V, et al. RGD peptides induce apoptosis by direct caspase-3 activation [J]. Nature,1999,397(6719):534-539
[36]Yin Y X, Liu Y X, Jin Y J, et al. PAC1 phosphatase is a transcription target of p53 in signalling apoptosis and growth suppression [J]. Nature,2003,422(6931):527-531
[37]Park J M, Greten F R, Li Z W, et al. Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition [J]. Science,2002,297(5589):2048-2051
[38]Cheung P C K, Zhang M, Chiu L C M, et al. Cell-cycle arrest and apoptosis induction in human breast carcinoma MCF-7 cells by carboxymethylated beta-glucan from the mushroom sclerotia of Pleurotus tuber-regium [J]. Carbohydrate Polymers,2006,66(4):455-462
[39]Ichijo H, Nishida E, Irie K, et al. Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways [J]. Science,1997,275(5296):90-94
[40]Fukuyo Y, Kitamura T, Inoue M, et al. Phosphorylation-dependent lys(63)-linked polyubiquitination of daxx is essential for sustained TNF-a-induced ASK1 activation [J]. Cancer Research,2009,69(19):7512-7517
[41]Hosokawa Y, Suzuki H, Suzuki Y, et al. Antiapoptotic function of apoptosis inhibitor 2-MALT1 fusion protein involved in t(11;18)(q21;q21) mucosa-associated lymphoid tissue lymphoma [J]. Cancer Research,2004,64(10):3452-3457
[42]Rangasamy V, Mishra R, Mehrotra S, et al. Estrogen suppresses MLK3-mediated apoptosis sensitivity in ER(+) breast cancer cells [J]. Cancer Research,2010,70(4):1731-1740
[43]Stoica G E, Franke T F, Moroni M, et al. Effect of estradiol on estrogen receptor-α gene expression and activity can be modulated by the ErbB2/PI 3-K/Akt pathway [J]. Oncogene, 2003,22(39):7998-8011
[44]Diaz-Cruz E S, Furth PA. Deregulated estrogen receptor a and p53 heterozygosity collaborate in the development of mammary hyperplasia [J]. Cancer Research,2010,70(10):3965-3974
[45]Thordarson G, Mendoza R A, Enriquez M I, et al. Interactions between IGF-I, estrogen receptor-a (ER a), and ER β in regulating growth/apoptosis of MCF-7 human breast cancer cells [J]. Journal of Endocrinology,2011,208(1):1-9
[2]Wasser S P. Current findings, future trends, and unsolved problems in studies of medicinal mushrooms [J]. Applied Microbiology and Biotechnology,2011,89(5):1323-1332
[3]Miles P G, Chang S T. Mushroom biology-concise basics and current developments [J]. Singapore: World Scientific,1997,144.
[4]陈娟,苏开美.食用菌遗传育种及种质鉴定研究进展[J].中国食用菌,2008,27(5)：3-8.
[5]Rathee S, Rathee D, Rathee D, et al. Mushrooms as therapeutic agents [J]. Revista Brasileira de Farmacognosia-Brazilian Journal of Pharmacognosy.2012,22(2):459-474.
[6]Wasser S P. Medicinal mushroom science:history, current Status, future trends, and unsolved problems [J]. International Journal of Medicinal Mushrooms,2010,12(1):1-16
[7]Dotan N, Wasser S P, Mahajna J. The culinary-medicinal mushroom Coprinus comatus as a natural antiandrogenic modulator [J]. Integrative Cancer Therapies,2011,10(2):148-59.
[8]Mattila P, Suonpaa K, Piironen V. Functional properties of edible mushrooms [J]. Nutrition,2000, 16(7/8):694-696.
[9]Zaidman B Z, Yassin M, Mahajna J, et al. Medicinal mushroom modulators of molecular targets as cancer therapeutics [J]. Applied Microbiology and Biotechnology,2005,67(4):453-468.
[10]Dai Y C, Yang Z L, Cui B K, et al. Species diversity and utilization of medicinal mushrooms and Fungi in China (Review) [J]. International Journal for Medicinal Mushrooms,2009,11(3): 287-302.
[11]Aida F M N A, Shuhaimi M, Yazid M, et al. Mushroom as a potential source of prebiotics:a review [J]. Trends in Food Science & Technology,2009,20(11-12):567-575
[12]Chang S T. Global impact of edible and medicinal mushrooms on human welfare in the 21st century: nongreen revolution [J]. International Journal for Medicinal Mushrooms,1999,1:1-8.
[13]Wasser S P, Weis A L. Medicinal properties of substances occurring in higher Basidiomycetes mushrooms:current perspectives (review) [J]. International Journal for Medicinal Mushrooms, 1999,1:31-62.
[14]Mizuno T. The extraction and development of antitumor-active polysaccharides from medicinal mushrooms in Japan (review) [J]. International Journal for Medicinal Mushrooms,1999,1: 9-29.
[15]Reshetnikov S V, Tan K K. Higher Basidiomycota as source of antitumor and immunostimulating polysaccharides [J]. International Journal for Medicinal Mushrooms,2001,3:361-394.
[16]Wasser S P. Medicinal mushrooms:ancient traditions, contemporary knowledge, and scientific enquiries [J]. International Journal for Medicinal Mushrooms,2007,9(3/4):187-189.
[17]Van Griensven L J L D. Culinary-medicinal mushrooms:must action be taken? [J] International Journal for Medicinal Mushrooms,2009,11(3):281-286.
[18]Bohn J A, BeMiller J N. (1-3)-β-D-glucans as biological response modifiers:a review of structure-functional activity relationships [J]. Carbohydrate Polymers,1995,28:3-14.
[19]Sarkar S, Koga J, Whitley R J, et al. Antiviral effect of the extract of culture medium of Lentinus edodes mycelia on the replication of herpes simplex virus type 1 [J]. Antiviral Research,1993, 20(4):293-303.
[20]Matsuyama H, Mangindaan R E, Yano T. Protective effect of schizophyllan and scleroglucan against Streptococcus sp. infection in Yellow Tail (Seriola quinqueradiata) [J]. Aquaculture, 1992,101:197-203.
[21]Oh K W, Lee C K, Kim Y S, et al. Antiherpetic activites of acidic protein bound polysaccharide isolated from Ganoderma lucidum alone and in combinations with acyclovir and vidarabine [J]. Journal of Ethnopharmacology,2000,72:221-227.
[22]Tsukagoshi S. Krestin (PSK) [J]. Cancer Treat Review,1984,11:131-55.
[23]Ooi V E C. Pharmacological studies on certain mushroom from China [J]. International Journal of Medicinal Mushrooms,2001,3:341-354.
[24]Lin W H, Hung C H, Hsu C I, et al. Dimerzation of the Nterminal amphipathic α-helix domain of the fungal immunomodulatory protein from Ganoderma tsugae (Fip-gts) defined by a yeast two-hybride system and site-directed mutagenesis [J]. Journal of Biological Chemistry,1997, 272:20044-20048.
[25]E1-Mekkawy S, E1-Mekkawy S, Meselhy M R, et al. Anti-HIV-1 and anti-H1V-1-protease substances from Ganoderma lucidum [J]. Phytochemistry,1998,49:1651-1657.
[26]Chairul, Tokuyama T, Hayashi Y, et al. Applanoxidic acids A, B, C and D, biologically active tetracyclic triterpenes from Ganoderma applanatum [J]. Phytochemistry,1991,30:4105-4109.
[27]Toth J O, Luu B, Ourisson G. Ganoderic acid T and Z:cytotoxic triterpenes from Ganoderma lucidum (Polyporaceae) [J]. Tetrahedron Letters,1983,24:1081-1084.
[28]Kohda H, Tokumoto W, Sakamoto K, et al. The biologically active constituents of Ganoderma lucidum (Fr.) Karst, histamine release-inhibitory triterpenes [J]. Chemical and Pharmaceutical Bulletin,1985,33:1367-1374.
[29]Morigiwa A, Kitabatake K, Fujimoto Y, et al. Angiotensin converting enzyme-inhibitory triterpenes from Ganoderma lucidum [J]. Chemical and Pharmaceutical Bulletin,1986,34:3025-3028.
[30]Lin C N, Tome W P. Novel cytotoxic principle of Formosan Ganoderma lucidum [J]. Journal of Natural Products,1991,54:998-1002.
[31]Bok J W, Lermer L, Chilton J, et al. Antitumor sterols from the mycelia of Cordyceps sinensis [J]. Phytochemistry,1999,51:891-898.
[32]Keller A C, Maillard M P, Hostettmann K. Antimicrobial steroids from the fungus Fomitopsis pinicola [J]. Phytochemistry,1996,41:1041-1046.
[33]Menoli R C R, Mantovani M S, Ribeiro L R, et al. Antimutagenic effects of the mushroom Agaricus blazei Murrill extracts on V79 cells [J]. Mutation Research,2001,496:5-13.
[34]Moradali M F, Mostafavi H, Hedjaroude G A, et al. Investigation of antibacterial potentiality of methanol extraction from fungus Ganoderma applanatum. World Conference on Magic Bullets Celebrating Paul Ehrlich 150th Birthday, Nurnberg, Germany,2004.
[35]Chiu S W,Wang Z M, Leung T M, et al. Nutritional value of Ganoderma extract and assessment of its genotoxicity and antigenotoxicity using comet assay of mouse lymphocytes [J]. Food and Chemical Toxicology,2000,38:173-178.
[36]Shimizu A, Yano T, Saito Y, et al. Isolation of an inhibitor of platelet aggregation from a fungus, Ganoderma lucidum [J]. Chemical and Pharmaceutical Bulletin,1985,33:3012-3015.
[37]Gottlieb D. Viomycin In:Gottlicb D, Shaw P D, eds. Antibiotics I, Mechanism of action [M], Springer-Verlag Berlin; 1967,677-680.
[38]Wasser S P. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides [J]. Applied Microbiology and Biotechnology,2002,60:258-274.
[39]汪建敏,焦阳,吕凤霞,等.食药用真菌翅鳞伞菌丝体蛋白活性的研究[J].江西农业学报,2008,20(8)：99-101.
[40]赵海珍,王娟,吕凤霞,等.翅鳞伞AS5.245胞内粗多糖抗肿瘤作用的研究[J].食品科学,2008,29(12)：678-680.
[41]Chang S T, Miles P G. The nutritional attributes of edible mushrooms [M]. In Mushrooms: Cultivation, Nutritional Value, Medicinal Effect, and Environmental Impact. Boca Raton, FL: CRC Press,2004,27-38.
[42]Kasuga A, Aoyagi Y, Sugahara T. Antioxidative activities of several mushroom extracts [J]. Journal of the Japanese Society for Food Science and Technology,1993,40:56-63.
[43]Mau J L, Chao G R, Wu K T. Antioxidant properties of methanolic extracts from several ear mushrooms [J]. Journal of Agricultural and Food Chemistry,2001,49:5461-5467.
[44]Yang J H, Lin H C, Mau J L. Antioxidant properties of several commercial mushrooms [J]. Food Chemistry,2002,77:229-235.
[45]Mau J L, Lin H C, Song S F. Antioxidant properties of several specialty mushrooms [J]. Food Research International,2002,35:519-526.
[46]Tsai S Y, Huang S J, Mau J L. Antioxidant properties of hot-water extracts from Agrocybe cylindracea [J]. Food Chemistry,2006,98:670-677.
[47]Lee Y L, Yen M T, Mau J L. Antioxidant properties of various extracts from Hypsizigus marmoreus [J]. Food Chemistry,2007,104:1-9.
[48]Lo KM, Cheung PCK. Antioxidant activity of extracts from the fruiting bodies of Agrocybe aegerita var. alba [J]. Food Chemistry,2005,89:533-539.
[49]Elmastas M, Isildak O, Turkekul I, Temur N. Determination of antioxidant activity and antioxidant compounds in wild edible mushrooms [J]. Journal of Food Composition and Analysis,2007,20: 337-345.
[50]Shon M Y, Kim T H, Sung N J. Antioxidants and free radical scavenging activity of Phellinus baumii (Phellinus of Hymenochaetaceae) extracts [J]. Food Chemistry,2003,82:593-597.
[51]Luo J G, Liu J, Sun Y, et al. Medium optimization, preliminary characterization and antioxidant activity in vivo of mycelial polysaccharide from Phellinus baumii Pilat [J]. Carbohydrate Polymers,2010,81:533-540.
[52]Reis FS, Martins A, Barros L, et al. Antioxidant properties and phenolic profile of the most widely appreciated cultivated mushrooms:a comparative study between in vivo and in vitro samples [J]. Food and Chemical Toxicology,2012, doi:10.1016/j.fct.2012.02.013.
[53]Palacios I, Lozano M, Moro C, et al. Antioxidant properties of phenolic compounds occurring in edible mushrooms [J]. Food Chemistry,2011,128:674-678.
[54]Liu Y T, Sun J, Luo Z Y, et al. Chemical composition of five wild edible mushrooms collected from Southwest China and their antihyperglycemic and antioxidant activity [J]. Food and Chemical Toxicology,2012, doi:10.1016/j.fct.2012.01.023.
[55]Ishikawa Y, Marimoto K, Hamasaki T. Flavoglaucin, a metabolite of Eurotium chavalieri, its oxidation and synergism with tocopherol [J]. Journal of the American Oil Chemists'Society, 1984,61:1864-1868.
[56]Tokita F, Shibukawa N, Yasumoto T, et al. Isolation and chemical structure of the plasma-cholesterol reducing substance from Shiitake mushroom [J]. Mushroom Science,1972,8: 783-788.
[57]Suzuki S, Ohshima S. Influence of shiitake (Lentinus edodes) on human serum cholesterol [J]. Mushroom Science,1976,9,463-470.
[58]Bobek P, Ozdin L, Galbavy S. Dose-and time-dependent hypocholesterolemic effect of oyster mushroom(Pleurotus ostreatus) in rats [J]. Nutrition,1998,14:282-286.
[59]Fukushima M, Nakano M, Morii Y, et al. Hepatic LDL receptor mRNA is increased by dietary mushroom (Agaricus bisporus) fiber and sugar beet fiber [J]. Journal of Nutrition,2000,130: 2151-2156.
[60]Ng Y F. In vitro and in vivo antioxidant activity and hypocholesterolemic effect in extracts of Agrocybe aegerita. M.Phil, thesis. Hong Kong:The Chinese University of Hong Kong.2005.
[61]Chen J J, Mao D, Yong Y Y, et al. Hepatoprotective and hypolipidemic effects of water-soluble polysaccharidic extract of Pleurotus eryngii [J]. Food Chemistry,2012,130(3):687-694.
[62]崔莉,董明盛,陈晓红,等.一株纤溶酶产生菌-蛹虫草的形态和分子鉴定[J].江苏农业学报,2010,26(3)：667-669.
[63]Kiho T, Kochi M, Usui S, et al. Antidiabetic effect of an acidic polysaccharide (TAP) from Tremella aurantia Schw.:Fr. (Heterobasidiomycetes) in genetically diabetic KKAy mice [J]. International Journal of Medicinal Mushrooms,2002,4:291-297.
[64]Swanston-Flatt S K, Day C, Flatt P R, et al. Glycemic effects of traditional European plant treatments for diabetes:Studies in normal and streptozotocin diabetic mice [J]. Diabetes Research and Clinical Practice,1989,10:69-73.
[65]Kurushima H, Kodama N, Nanba H. Activities of polysaccharides obtained from Grifola frondosa on insulin-dependent diabetes mellitus induced by streptozotocin in mice [J]. Mycoscience,2000, 41:473-480.
[66]Kiho T, Morimoto H, Kobayashi T, et al. Effect of a polysaccharide (TAP) from the fruiting bodies of Tremella aurantia on glucose metabolism in mouse liver [J]. Bioscience, Biotechnology, and Biochemistry,2000,64:417-419.
[67]Gao Y, Lan J, Dai X, et al. A phase Ⅰ/Ⅱ study of ling zhi mushroom Ganoderma lucidum (W.Curt.:Fr.) Lloyd (Aphyllophoromycetidae) extract in patients with type II diabetes mellitus [J]. International Journal of Medicinal Mushrooms,2004,6:33-39.
[68]Eo S K, Kim Y S, Lee C K, et al. Antiviral activities of various water and methanol soluble substances isolated from Ganoderma lucidum [J]. Journal of Ethnopharmacology,1999,68: 129-136.
[69]Takazawa H, Tajima F, Miyashita C. An antifungal compound from "Shiitake" (Lentinus edodes) [J]. Yakugaku Zasshi,1982,102:489-491.
[70]Mothana R A A, Jansen R, Julich W D, et al. Ganomycin A and B, new antimicrobial farnesyl hydroquinones from the basidiomycete Ganoderma pfeifferi [J]. Journal of Natural Products, 2000,63:416-418.
[71]Badalyan S M. Antiprotozoal activity and mitogenic effect of mycelium of culinary-medicinal shiitake mushroom Lentinus edodes (Berk.) Singer (Agaricomycetidae) [J]. International Journal of Medicinal Mushrooms,2004,6:131-138.
[72]Brandt C R, Piraino F. Mushroom antivirals [J]. Antimicrobial Agents and Chemotherapy\Antimicrob. Agents Chemother,2000,4:11-26.
[73]Mothana R A A, Awadh N A A, Jansen R, et al. Antiviral lanostanoid triterpenes from the fungus Ganoderma pfeifferi Bres [J]. Fitoterapia,2003,74:177-180.
[74]Awadh A A N, Mothana R A A, Lesnau A, et al. Antiviral activity of extracts and compounds from Inonotus hispidus [J]. Fitoterapia,2003,74:483-485.
[75]Sano M, Yoshino K, Matsuzawa T, et al. Inhibitory effects of edible higher basidiomycetes mushroom extracts on mouse type Ⅳ allergy [J]. International Journal of Medicinal Mushrooms, 2002,4:37-41.
[76]Ali N A A, Pilgrim H, Ludke J, et al. Inhibition of chemiluminescence response of human mononuclear cells and suppression of mitogeninduced proliferation of spleen lymphocytes of mice by hispolon and hispidin [J]. Pharmazie,1996,51:667-670.
[77]Chen R Y, Yu D Q. Studies on the triterpenoid constituents of the spores from Ganoderma lucidum Karst [J]. Journal of Pharmaceutical Sciences,1993,2:91-96.
[78]Wang M Y, Liu Q, Che Q M, et al. Effects of total triterpenoids extract from Ganoderma lucidum (Curt.:Fr.) P.Karst. (Reishi Mushroom) on experimental liver injury models induced by carbon tetrachloride or d-galactosamine in mice [J]. International Journal of Medicinal Mushrooms, 2002,4:337-342.
[79]Gao Y, Zhou S, Chen G, et al. A phase Ⅰ/Ⅱ study of a Ganoderma lucidum (Curt.:Fr.) P.Karst. (Ling Zhi, Reishi mushroom) extract in patients with chronic hepatitis B [J]. International Journal of Medicinal Mushrooms,2002,4:2321-2327.
[80]Nada S A, Omara E A, Abdel-Salam O M E, et al. Mushroom insoluble polysaccharides prevent carbon tetrachloride-induced hepatotoxicity in rat [J]. Food and Chemical Toxicology,2010,48: 3184-3188.
[81]Gibson G R, Probert H M, Rastall R A, et al. Dietary modulation of the human colonic microbiota: updating the concept of prebiotics [J]. Nutrition Research Reviews,2004,17:259-275.
[82]Macfarlane S, Macfarlane G T, Cumming J H. Review article:prebiotics in the gastrointestinal tract [J]. Alimentary Pharmacology and Therapeutics,2006,24:701-714.
[83]Douglas L C, Sanders M E. Probiotics and prebiotics in dietetics practice [J]. Journal of the American Dietetic Association,2008,108:510-521.
[84]Wang Y. Prebiotics:present and future in food science and technology [J]. Food Research International,2009,42:8-12.
[85]Vetter J. Chitin content of cultivated mushrooms Agaricus bisporus, Pleurotus ostreatus and Lentinula edodes [J]. Food Chemistry,2007,102:6-9.
[86]Tao Y, Zhang L, Cheung P C K. Physicochemical properties and antitummor activities of water-soluble native and sulfated hyperbranched mushroom polysaccharides [J]. Carbohydrate Research,2006,341:2261-2269.
[87]Van Loo J. Inulin-type fructans as prebiotics. In G. R. Gibson, & R. A. Rastall (Eds.), Prebiotics: Development and application (pp.59). Hoboken, NJ:John Wiley & Sons,2006.
[88]Synytsya A, Mickova K, Synytsya A, et al. Glucans from fruit bodies of cultivated mushrooms Pleurotus ostreatus and Pleurotus eryngii:structure and potential prebiotic activity [J]. Carbohydrate Polymers,2009,76(4):548-556.
[89]Luo J J, Liu J, Ke C L,et al. Optimization of medium composition for the production of exopolysaccharides from Phellinus baumii Pilot in submerged culture and the immuno-stimulating activity of exopolysaccharides [J]. Carbohydrate Polymers,2009,78(3): 409-415.
[90]方庆华,钟建江.灵芝真菌发酵生产灵芝多糖和灵芝酸[J].华东理工大学学报,2001,27(3)： 254-257.
[91]夏志兰,俞挑生,周连玉,等.灵芝液体发酵条件的优化研究[J].微生物学杂志,2007,27(2)：10-15.
[92]邢燕,杨晓彤,杨庆尧,等.灵芝液体深层发酵研究进展[J].工业微生物,2007,37(3)：63-67
[93]刘忠义,曾虹燕.茯苓液体培养研究初探[J].湘潭大学自然科学学报,2002,24(4)：49-51.
[94]王谦,闫蕾蕾,王超.茯苓液体培养条件研究及其营养浓缩液的相关检测[J].食用菌学报,2003,10(2)：17-20.
[95]李羿,万德光,裴瑾.茯苓液体发酵条件的研究[J].成都中医药大学学报,2005,28(1)：52-55.
[96]尚德静,王孝敏.冬虫夏草深层发酵的研究[J].中国食用菌,1996,15(6)：48-49.
[97]钟士清,胡文峰,罗国威.冬虫夏草头孢菌菌丝体液体发酵条件研究[J].华南农业大学学报,1995,16(3)：108-111.
[98]王允祥,陆兆新.翅鳞伞培养条件响应面法优化研究[J].微生物学通报,2004,31(6)：42-47.
[99]Zhao H Z, Wang J, Lu Z X. Optimization of process parameters of the Pholiota squarrosa extracellular polysaccharide by Box-Behnken statistical design [J]. Carbohydrate Polymers,2009, 77 (3):677-680.
[100]刘少琴,赵紫华,马彩霞,等.药用真菌液体发酵培养的研究进展[J].中国现代中药,2006,8(7)：28-31,35.
[101]Ruiz-Herrera J. Fungal cell wall:Structure, synthesis, and assembly [M]. Boca Raton, Ann Arbor, London:CRC press,1956.
[102]Sietsman J H, Wessels J G H. Evidence for covalent linkages between chitin and β-glucan in a fungal wall [J]. Journal of Genetic Microbiology,1979,114,99-105.
[103]Mizuno T, Ohsawa K, Hagiwara N, et al. Fractionation and characterization of antitumor polysaccharides from Maitake, Grifola frondosa [J]. Agricultural Biology and Chemistry,1986, 50:1679-1688.
[104]Mizuno T, Hagiwara T, Nakamura T, et al. Antitumor activity and some properties of water-soluble polysaccharides from "Himematsutake", the fruiting body of Agaricus blazei Murrill [J]. Agricultural Biology and Chemistry,1990,54:2889-2896.
[105]Zhang M, Cui S W, Cheung P C K, et al. Antitumor polysaccharides from mushrooms:a review on their isolation process, structural characteristics and antitumor activity [J]. Trends in Food Science & Technology,2007,18:4-19.
[106]Nauts H C, Swift W E, Coley B L. The treatment of malignant tumors by bacterial toxins as developed by the late William B. Coley, reviewed in the light of modern research [J]. Cancer Research,1946,6:205-214.
[107]Chihara G. The antitumor polysaccharide lentinan:an overview. In T. Aoki, et al. (Eds.), Manipulation of host defense mechanism [J]. Nature,1969,222:687-694.
[108]Ikekawa T. Beneficial effects of edible and medicinal mushrooms in health care [J]. International Journal Medical Mushrooms,2001,3:291-298.
[109]Ooi V E C, Liu F. A review of pharmacological activities of mushroom polysaccharides [J]. International Journal of Medicinal Mushrooms,1999,1:195-206.
[110]Maeda Y Y, Chihara G. Lentinan, a new immunoaccelerator of cells-mediated responses [J]. Nature,1971,229:634-647.
[111]Chihara G. Immunopharmacology of lentinan, a polysaccharide isolated from lentinus edodes:its application as a host defense potentiator [J]. International Journal Oriental Medicine,1992,17: 57-77.
[112]Maeda Y Y, Watanabe S T, Chihara C, et al. Denaturation and renaturation of α β-1,6;1,3-glucan, lentinan, associated with expression of T-cell-mediated responses [J]. Cancer Research,1988,48: 671-675.
[113]Suzuki M, Iwashiro M, Takatsuki F, et al. Reconstitution of antitumor effects of lentinan in nude mice:roles of delayed-type hypersensitivity reaction triggered by CD4-positive T cell clone in the infiltration of effector cells into tumor [J]. Japanese Journal of cancer Research,1994,85: 409-417.
[114]Taki H, Ohishi K, Okano A, et al. Antimetastatic effect of lentinan on liver metastasis of colon carcinoma (Colon 26):possible role of activated Kupffer cells [J]. International Journal of Immunotherapy,1995,11,29-38.
[115]Wang Y Y, Khoo K H, Chen S T, et al. Studies on the immuno-modulating and antitumor activities of Ganoderma lucidum (Reishi) polysaccharides:functional and proteomic analyses of a fucose-containing glycoprotein fraction responsible for the activities [J]. Bioorganic Medical Chemistry,2002,10:1057-1062.
[116]Chen Y Y, Chang H M. Antiproliferative and differentiating effects of polysaccharide fraction from fu-ling (Poria cocos) on human leukemic U937 and HL-60 cells [J]. Food and Chemical Toxicology,2004,42:759-769.
[117]Li G, Kim D, Kim T, et al. Protein-bound polysaccharide from Phellinus linteus induces G2/M phase arrest and apoptosis in SW480 human colon cancer cells [J]. Cancer Letters,2004,216: 175-181.
[118]Lin X, Cai Y, Li Z, et al. Structure determination, apoptosis induction, and telomerase inhibition of CEP-2, a novel lichenin from Cladonia furcata [J]. Biochimica et Biophysica Acta,2003,1622, 99-108.
[119]Chow L, Lo W, Loo C S, et al. Polysaccharide peptide mediates apoptosis by up-regulating p21 gene and and down-regulating cyclin D1 gene [J]. American Journal Chinese Medicine,2003,31: 1-9.
[120]Zhang M, Cheung P C K, Chiu L C M, et al. Cell-cycle arrest and apoptosis induction in human breast carcinoma MCF-7 cells by carboxymethylated β-glucan from the mushroom sclerotia of Pleurotus tuber-regium [J]. Carbohydrate Polymers,2006,66:455-462.
[121]Kawamura M, Kasai H. Delayed cell cycle progression and apoptosis induced by hemicellulase-treated Agaricus blazei [J]. Evidence-Based Complementary and Alternative Medicine,2007,4(1):83-94.
[122]Yeh W C, Dompa J L, Mccarrach M E, et al. FADD:essential for embryo development and signaling from some, but not all, inducer of apoptosis [J]. Science,1998,279:1954-1955.
[123]Enari M, Sakahira H, Yokoyama H, et al. A caspase-activated DNase that degades DNA during apoptosis, and its inhibitor ICAD [J]. Nature,1998,392:43-50.
[124]Xu H S, Wu Y W, Xu S F, et al. Antitumor and immunomodulatory activity of polysaccharides from the roots of Actinidia eriantha [J]. Journal of Ethnopharmacology,2009,125:310-317.
[125]Zheng R, Su J, Dai H, et al. Characterization and immunomodulating activities of polysaccharide from Lentinus edodes [J]. International Immunopharmacology,2005,5:811-820.
[126]冯优,王凤山,张天民,等.多糖类药物的研究进展[J].中国生化药物杂志,2008,2：129-133,139.
[127]张延坤,张东祥.生物活性多糖的抗肿瘤作用及其机制研究进展[J].解放军预防医学杂志,2006,24：382-385.
[128]冯文茹.我国天然抗肿瘤活性成分的研究进展[J].中华医学研究杂志,2007,7(9)：801-803.
[129]陈执中.天然药物抗癌活性成分研究进展[J].中国民族民间医药杂志,2004,70：249-251.
[130]Vandana S, Arvind S N, Kumar J K, et al. Plant-based anticancer molecules:A chemical and biological profile of some important leads [J]. Bioorganic & Medicinal Chemistry,2005,13: 5892-5908.
[131]Ma X, Wang Z. Anticancer drug discovery in the future:an evolutionary perspective [J]. Drug Discovery Today,2009,14:1137-1142.
[132]Vidi J, Sivakami S, Shahani S, et al. Antihyperglycemic dffects of three extracts from Momordica and Charantia [J]. Journal of ethnopharmacology,2003,88:107.
[133]于红,张学成.螺旋藻多糖对HeLa细胞生长的影响[J].中国海洋药物,2003,22：26.
[134]Yang L, Zhang L. Chemical structural and chain conformational characterization of some bioactive polysaccharides isolated from natural sources [J]. Carbohydrate Polymers,2009,76:349-361.
[135]Bi Z S, Li TH, Zheng G Y, et al. Four new species of Agariacales [J]. Acta Mycologica Sinica, 1985,4:155-161.
[136]Kirk P M, Cannon PF, Minter DW, et al. Dictionary of the Fungi. (10th ed.) [M]. Wallingford: CABI.2008.
[137]Cui Y J, Li Q Z. Immune effect of Pholiota nameko polysaccharide on the aging model mice in the different period [J]. Journal of Northeast Agricultural University,2004,35(2):159-161.
[138]Li H, Lu X, Zhang S, et al. Anti-inflammatory activity of polysaccharide from Pholiota nameko [J]. Biochemistry (Mosc),2008,73:669-675.
[139]Li H, Wang S. Kinetics of inhibition of ribonuclease A by Pholiota Nameko polysaccharide [J]. International Journal of Biological Macromolecules,2007,40:134-138.
[140]Li H, Zhang M, Ma G. Hypolipidemic effect of the polysaccharide from Pholiota nameko [J]. Nutrition,2010,26:556-562.
[141]Zhao H, Wang J, Lu Z. Optimization of process parameters of the Pholiota squarrosa extracellular polysaccharide by Box-Behnken statistical design [J]. Carbohydrate Polymers,2009,77, 677-680.
[142]Zou S, Zhang X, Yao W, et al. Structure characterization and hypoglycemic activity of a polysaccharide isolated from the fruit of Lycium barbarum L [J]. Carbohydrate Polymers,2010, 80:1161-1167.
[143]Jiang C, Wang M, Liu J, et al. Extraction, preliminary characterization, antioxidant and anticancer activities in vitro of polysaccharides from Cyclina sinensis [J]. Carbohydrate Polymers,2011, 84(3):851-857.
[144]Gan D, Ma L, Jiang C, et al. Production, preliminary characterization and antitumor activity in vitro of polysaccharides from the mycelium of Pholiota dinghuensis Bi [J]. Carbohydrate Polymers,2011,84(3):997-1003.
[1]Wasser S P. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides [J]. Applied Microbiology and Biotechnology,2002,60:258-274.
[2]Zaidman BZ, Yassin M, Mahajna J, et al. Medicinal mushroom modulators of molecular targets as cancer therapeutics [J]. Applied Microbiology and Biotechnology,2005,67(4):453-468.
[3]Chen W, Zhao Z, Chen, S F, et al. Optimization for the production of exopolysaccharide from Fomes fomentarius in submerged culture and its antitumor effect in vitro [J]. Bioresource Technology, 2008,99:3187-3194.
[4]Luo J, Liu J, Sun Y, et al. Optimization of Medium optimization, preliminary characterization and antioxidant activity in vivo of mycelial polysaccharide from Phellinus baumii Pilat [J]. Carbohydrate Polymers,2010,81:533-540.
[5]Moradali M F, Mostafavi H, Ghods S, et al. Immunomodulating and anticancer agents in the realm of macromycetes fungi (macrofungi) [J]. International Immunopharmacology,2007,7:701-724.
[6]Peng Y, Zhang L, Zeng F, et al. Structure and antitumor activities of the water-soluble polysaccharides from Ganoderma tsugae mycelium [J]. Carbohydrate Polymers,2005,59: 385-392.
[7]Zhang M, Cui S W, Cheung P C K, et al. Antitumor polysaccharides from mushrooms:a review on their isolation process, structural characteristics and antitumor activity [J]. Trends in Food Science and Technology,2007,18:4-19.
[8]Zhao L, Dong Y, Chen G, et al. Extraction, purification, characterization and antitumor activity of polysaccharides from Ganoderma lucidum [J]. Carbohydrate Polymers,2010,80:783-789.
[9]Cui Y J, Li Q Z. Immune effect of Pholiota nameko polysaccharide on the aging model mice in the different period [J]. Journal of Northeast Agricultural University,2004,35(2):159-161.
[10]Li H, Lu X, Zhang S, et al. Anti-inflammatory activity of polysaccharide from Pholiota nameko [J]. Biochemistry (Mosc),2008,73:669-675.
[11]Li H, Wang S. Kinetics of inhibition of ribonuclease A by Pholiota Nameko polysaccharide [J]. International Journal of Biological Macromolecules,2007,40:134-138.
[12]Li H, Zhang M, Ma G. Hypolipidemic effect of the polysaccharide from Pholiota nameko [J]. Nutrition,2010,26:556-562.
[13]Bi Z S, Li T H, Zheng G Y, et al. Four new species of Agariacales. Acta Mycologica Sinica [J],1985, 4:155-161.
[14]Kirk P M, Cannon P F, Minter D W, et al. Dictionary of the Fungi. (10th ed.) [M]. Wallingford: CABI.2008.
[15]Wasser S P. Current findings, future trends, and unsolved problems in studies of medicinal mushrooms [J]. Applied Microbiology and Biotechnology,2011,89(5):1323-1332.
[16]Cheung P C K. Dietary fiber content and composition of some cultivated edible mushroom fruiting bodies and mycelia [J]. Journal of Agricultural and Food Chemistry 1996,44:468-471.
[17]Aida F M N A, Shuhaimi M, Yazid M, et al. Mushroom as a potential source of prebiotics:a review [J]. Trends in Food Science and Technology,2009,20(11-12):567-575.
[18]Ho Y C, Norli I, Alkarkhi A, et al. Characterization of biopolymeric flocculant (pectin) and organic synthetic flocculant (PAM):A comparative study on treatment and optimization in kaolin suspension [J]. Bioresource Technology,2010,101(4):1166-1174.
[19]Francis F, Sabu A, Nampoothiri K. Use of response surface methodology for optimizing process parameters for the production of a-amylase by Aspergillus oryzae [J]. Biochemical Engineering Journal,2003,15(2):107-15.
[20]Liu C, Liu Y, Liao W, et al. Application of statistically based experimental designs for the optimization of nisin production from whey [J]. Biotechnology Letters,2003,25(11):877-82.
[21]Kshirsagar A C, Singhal R S. Optimization of starch oleate derivatives from native corn and hydrolyzed corn starch by response surface methodology [J]. Carbohydrate Polymers,2007,69: 455-461.
[22]Liu J, Luo J, Ye H, et al. Medium optimization and structural characterization of exopolysaccharides from endophytic bacterium Paenibacillus polymyxa EJS-3 [J]. Carbohydrate Polymers,2010,79: 206-213.
[23]Liu J, Luo J, Ye H, et al. Production, characterization and antioxidant activities in vitro of exopolysaccharides from endophytic bacterium Paenibacillus polymyxa EJS-3 [J]. Carbohydrate Polymers,2009,78:275-281.
[24]Pokhrel C P, Ohga S. Submerged culture conditions for mycelial yield and polysaccharides production by Lyophyllum decastes [J]. Food Chemistry,2007,105:641-646.
[25]Bae J T, Sinha J, Park J P, et al. Optimization of submerged culture conditions for exo-biopolymer production by Paecilomyces japonica [J]. Journal of Microbiology and Biotechnology,2000,10: 482-497.
[26]Kim H O, Lim J M, Joo S W, et al. Optimization of submerged culture condition for the production of mycelial biomass and exopolysaccharide by Agrocybe cylindracea [J]. Bioresource Technology, 2005,96:1175-1182.
[27]Gan D, Ma L P, Jiang C X, et al. Production, preliminary characterization and antitumor activity in vitro of polysaccharides from the mycelium of Pholiota dinghuensis Bi. Carbohydrate Polymers 2011,84:997-1003
[28]王允祥,陆兆新.翅鳞伞培养条件响应面法优化研究[J].微生物学通报,2004,31(6)：42-47.
[29]Zhao H Z, Wang J, Lu Z X. Optimization of process parameters of the Pholiota squarrosa extracellular polysaccharide by Box-Behnken statistical design. Carbohydrate Polymers,2009,77 (3):677-680.
[1]Wasser S P. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides [J]. Applied Microbiology and Biotechnology,2002,60(3):258-274
[2]Zaidman B Z, Yassin M, Mahajna J, et al. Medicinal mushroom modulators of molecular targets as cancer therapeutics [J]. Applied Microbiology and Biotechnology,2005,67(4):453-468
[3]Wasser S P. Current findings, future trends, and unsolved problems in studies of medicinal mushrooms [J]. Applied Microbiology and Biotechnology,2011,89(5):1323-1332
[4]Aida F M N A, Shuhaimi M, Yazid M, et al. Mushroom as a potential source of prebiotics:a review [J]. Trends in Food Science & Technology,2009,20(11-12):567-575
[5]Nada S A, Omara E A, Abdel-Salam O M E, et al. Mushroom insoluble polysaccharides prevent carbon tetrachloride-induced hepatotoxicity in rat [J]. Food and Chemical Toxicology,2010, 48(11):3184-3188
[6]Kozarski M, Klaus A, Niksic M, et al. Antioxidative and immunomodulating activities of polysaccharide extracts of the medicinal mushrooms Agaricus bisporus, Agaricus brasiliensis, Ganoderma lucidum and Phellinus linteus [J]. Food Chemistry,2011,129(4):1667-1675
[7]Gan D, Ma L P, Jiang C X, et al. Production, preliminary characterization and antitumor activity in vitro of polysaccharides from the mycelium of Pholiota dinghuensis Bi [J]. Carbohydrate Polymers,2011,84(3):997-1003
[8]Mahajna J, Dotan N, Zaidman B Z, et al. Pharmacological Values of Medicinal Mushrooms for Prostate Cancer Therapy:The Case of Ganoderma Lucidum [J]. Nutrition and Cancer-an International Journal,2009,61(1):16-26
[9]Zhang M, Cui S W, Cheung P C K, et al. Polysaccharides from mushrooms:a review on their isolation process, structural characteristics and antitumor activity [J]. Trends in Food Science & Technology,2006,18(1):4-19
[10]Vaz J A, Barros L, Martins A, et al. Chemical composition of wild edible mushrooms and antioxidant properties of their water soluble polysaccharidic and ethanolic fractions [J]. Food Chemistry,2011,126(2):610-616
[11]Dubois M, Gilles K A, Hamilton J K, et al. Colorimetric method for determination of sugars and related substances [J]. Analytical Chemistry,1956,28,350-356.
[12]Blumenkrantz M, Asboe-Hansen G. New method for quantitative determination of uronic acids [J]. Analytical Biochemistry,1973,54,484-489.
[13]Bradford M M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding [J]. Analytical Biochemistry,1976,72,248-254.
[14]Kawai Y, Seno N, Anno K. A modified method for chondrosulfatase assay [J]. Analytical Biochemistry,1969,32,314-321.
[15]Liu J, Luo J G, Ye H, et al. Production, characterization and antioxidant activities in vitro of exopolysaccharides from endophytic bacterium Paenibacillus polymyxa EJS-3 [J]. Carbohydrate Polymers,2009,78(2):275-281
[16]Qiao D, Hu B, Gan D, et al. Extraction optimized by using response surface methodology, purification and preliminary characterization of polysaccharides from Hyriopsis cumingii [J]. Carbohydrate Polymers,2009,76(3):422-429
[17]Maciel J S, Chaves L S, Souza B W S, et al. Structural characterization of cold extracted fraction of soluble sulfated polysaccharide from red seaweed Gracilaria birdiae [J]. Carbohydrate Polymers, 2008,71(4):559-565
[18]Peng Y F, Zhang L N, Zeng F B, et al. Structure and antitumor activities of the water-soluble polysaccharides from Ganoderma tsugae mycelium [J]. Carbohydrate Polymers,2005,59(3): 385-392
[19]Liu C H, Li X D, Li Y H, et al. Structural characterisation and antimutagenic activity of a novel polysaccharide isolated from Sepiella maindroni ink [J]. Food Chemistry,2008,110(4):807-813
[20]Zou S, Zhang X, Yao W B, et al. Structure characterization and hypoglycemic activity of a polysaccharide isolated from the fruit of Lycium barbarum L. [J]. Carbohydrate Polymers,2010, 80(4):1161-1167
[21]Yang L Q, Fu S S, Zhu X N, et al. Hyperbranched acidic polysaccharide from green tea [J]. Biomacromolecules,2010,11(12):3395-3405
[1]Hwang Y P, Choi J H, Jeong H G. Protective effect of the Aralia continentalis root extract against carbon tetrachloride-induced hepatotoxicity in mice [J]. Food and Chemical Toxicology, 2009,47(1):75-81
[2]Hsu Y W, Tsai C F, Chang W H, et al. Protective effects of Dunaliella salina-A carotenoids-rich alga, against carbon tetrachloride-induced hepatotoxicity in mice [J]. Food and Chemical Toxicology,2008,46(10):3311-3317
[3]Siegel R, Ward E, Brawley O, et al. Cancer statistics,2011:the impact of eliminating socioeconomic and racial disparities on premature cancer deaths [J]. CA Cancer J Clin,2011, 61(4):212-236
[4]Finkel T, Holbrook N J. Oxidants, oxidative stress and the biology of ageing [J]. Nature,2000, 408(6809):239-247
[5]Valko M, Leibfritz D, Moncol J, et al. Free radicals and antioxidants in normal physiological functions and human disease [J]. International Journal of Biochemistry & Cell Biology,2007, 39(1):44-84
[6]Sun J, Chu Y F, Wu X Z, et al. Antioxidant and anti proliferative activities of common fruits [J]. Journal of Agricultural and Food Chemistry,2002,50(25):7449-7454
[7]Aida F M N A, Shuhaimi M, Yazid M, et al. Mushroom as a,potential source of prebiotics:a review [J]. Trends in Food Science & Technology,2009,20(11-12):567-575
[8]Yoon H, Liu R H. Effect of selected phytochemicals and apple extracts on NF-kappa B activation in human breast cancer MCF-7 cells [J]. Journal of Agricultural and Food Chemistry, 2007,55(8):3167-3173
[9]Eberhardt M V, Lee C Y, Liu R H. Nutrition-Antioxidant activity of fresh apples [J]. Nature, 2000,405(6789):903-904
[10]Wasser S P. Current findings, future trends, and unsolved problems in studies of medicinal mushrooms [J]. Applied Microbiology and Biotechnology,2011,89(5):1323-1332
[11]Zhang M, Cui S W, Cheung P C K, et al. Polysaccharides from mushrooms:a review on their isolation process, structural characteristics and antitumor activity [J]. Trends in Food Science & Technology,2006,18(1):4-19
[12]Ke C, Sun L, Qiao D, et al. Antioxidant acitivity of low molecular weight hyaluronic acid [J]. Food and Chemical Toxicology,2011,49(10):2670-2675
[13]Qiao D, Ke C, Hu B, et al. Antioxidant activities of polysaccharides from Hyriopsis cumingii [J]. Carbohydrate Polymers,2009,78(2):199-204
[14]Luo J, Liu J, Sun Y, et al. Medium optimization, preliminary characterization and antioxidant activity in vivo of mycelial polysaccharide from Phellinus baumii Pilat [J]. Carbohydrate Polymers,2010,81(3):533-540
[15]Ye H, Wang K, Zhou C, et al. Purification, antitumor and antioxidant activities in vitro of polysaccharides from the brown seaweed Sargassum pallidum [J]. Food Chemistry,2008,111(2): 428-432
[16]Gan D, Ma L, Jiang C, et al. Production, preliminary characterization and antitumor activity in vitro of polysaccharides from the mycelium of Pholiota dinghuensis Bi [J]. Carbohydrate Polymers,2011,84(3):997-1003
[17]Fan G J, Tang J J, Bhadauria M, et al. Resveratrol ameliorates carbon tetrachloride-induced acute liver injury in mice [J]. Environmental Toxicology and Pharmacology,2009,28(3): 350-356
[18]Hsu Y W, Tsai C F, Chen W K, et al. Protective effects of seabuckthom(Hippophae rhamnoides L.) seed oil against carbon tetrachloride-induced hepatotoxicity in mice [J]. Food and Chemical Toxicology,2009,47(9):2281-2288
[19]Zaidman B Z, Yassin M, Mahajna J, et al. Medicinal mushroom modulators of molecular targets as cancer therapeutics [J]. Applied Microbiology and Biotechnology,2005,67(4):453-468
[20]Kozarski M, Klaus A, Niksic M, et al. Antioxidative and immunomodulating activities of polysaccharide extracts of the medicinal mushrooms Agaricus bisporus,Agaricus brasiliensis, Ganoderma lucidum and Phellinus linteus [J]. Food Chemistry,2011,129(4):1667-1675
[21]Chen J J, Mao D, Yong Y Y, et al. Hepatoprotective and. hypolipidemic effects of water-soluble polysaccharidic extract of Pleurotus eryngii [J]. Food Chemistry,2012,130(3):687-694
[22]Dhanasekaran M, Ignacimuthu S, Agastian P. Potential hepatoprotective activity of ononitol monohydrate isolated from Cassia tora L. on carbon tetrachloride induced hepatotoxicity in wistar rats [J]. Phytomedicine,2009,16(9):891-895
[23]Miesel R, Sanocka D, Kurpisz M, et al. Antiinflammatory effects of nadph oxidase-inhibitors [J]. Inflammation,1995,19(3):347-362
[24]Nada S A, Omara E A, Abdel-Salam O M E, et al. Mushroom insoluble polysaccharides prevent carbon tetrachloride-induced hepatotoxicity in rat [J]. Food and Chemical Toxicology,2010, 48(11):3184-3188
[25]Tsai C F, Hsu Y W, Chen W K, et al. Hepatoprotective effect of electrolyzed reduced water against carbon tetrachloride-induced liver damage in mice [J]. Food and Chemical Toxicology, 2009,47(8):2031-2036
[26]Shim J Y, Kim M H, Kim H D, et al. Protective action of the immunomodulator ginsan against carbon tetrachloride-induced liver injury via control of oxidative stress and the inflammatory response [J]. Toxicology and Applied Pharmacology,2010,242(3):318-325
[27]Park C M, Youn H J, Chang H K, et al. TOP1 and 2, polysaccharides from Taraxacum officinale, attenuate CC14-induced hepatic damage through the modulation of NF-kappa B and its regulatory mediators [J]. Food and Chemical Toxicology,2010,48(5):1255-1261
[28]Singh N, Kamath V, Narasimhamurthy K, et al. Protective effect of potato peel extract against carbon tetrachloride-induced liver injury in rats [J]. Environmental Toxicology and Pharmacology,2008,26(2):241-246
[1]Siegel R, Ward E, Brawley O, et al. Cancer statistics,2011:the impact of eliminating socioeconomic and racial disparities on premature cancer deaths [J]. CA-A Cancer Journal for Clinicians,2011, 61(4):212-236.
[2]World Health Organization. An update of the global burden of disease in 2004. Geneva, World Health Organization (forthcoming),2004.
[3]World Health Organization. World health statistics 2008. Geneva, World Health Organization,2009.
[4]Chabner B A, Roberts T G. Timeline-chemotherapy and the war on cancer [J]. Nature Reviews Cancer,2005,5:65-72
[5]Sawyers C. Targeted cancer therapy [J]. Nature,2004,432:294-297.
[6]冯文茹.我国天然抗肿瘤活性成分的研究进展[J].中华医学研究杂志,2007,7(9)：801-803.
[7]陈执中.天然药物抗癌活性成分研究进展[J].中国民族民间医药杂志,2004,70：249-251.
[8]Vandana S, Negi A, Kumar J, et al. Plant-based anticancer molecules:A chemical and biological profile of some important leads [J]. Bioorganic & Medicinal Chemistry,2005,13:5892-5908.
[9]Ma X, Wang Z. Anticancer drug discovery in the future:an evolutionary perspective [J]. Drug Discovery Today,2009,14:1137-1142.
[10]Yeh W, Dompa J, Mccarrach M, et al. FADD:essential for embryo development and signaling from some, but not all, inducer of apoptosis [J]. Science,1998,279,1954-1955.
[11]Enari M, Sakahira H, Yokoyama H, et al. A caspase-activated DNase that degades DNA during apoptosis, and its inhibitor ICAD [J]. Nature,1998,392,43-50.
[12]Xu H, WuY, Xu S, et al. Antitumor and immunomodulatory activity of polysaccharides from the roots of Actinidia eriantha [J]. Journal of Ethnopharmacology,2009,125,310-317.
[13]Ruan Z, Su J, Dai H, et al. Characterization and immunomodulating activities of polysaccharide from Lentinus edodes [J]. International Immunopharmacology,2005,5,811-820.
[14]冯优,王凤山,张天民,等.多糖类药物的研究进展[J].中国生化药物杂志,2008,2,129-133,139.
[15]张延坤,张东祥.生物活性多糖的抗肿瘤作用及其机制研究进展[J].解放军预防医学杂志,2006,24,382-385.
[16]Vidi J, Sivakami S, Shahani S, et al. Antihyperglycemic dffects of three extracts from Momordica and charantia [J]. Journal of ethnopharmacology,2003,88,107.
[17]于红,张学成.螺旋藻多糖对HeLa细胞生长的影响[J].中国海洋药物,2003,22,26.
[18]Yang L, Zhang L. Chemical structural and chain conformational characterization of some bioactive polysaccharides isolated from natural sources [J]. Carbohydrate Polymers,2009,76,349-361.
[19]Mosmann T. Rapid colorimetric assay for cellular growth and survival:Application to proliferation and cytotoxicity assays [J]. Journal of Immunological Methods,1983,65(1-2),55-63.
[20]Felice D L, Sun J, Liu R H. A modified methylene blue assay for accurate cell counting [J]. Journal of Functional Foods,2009,1(1):109-118
[21]Yoon H, Liu R H. Effect of 2alpha-hydroxyursolic acid on NF-kB activation induced by TNF-alpha in human breast cancer MCF-7 cells [J]. Journal of Agriculture and Food Chemistry,2008,56(18): 8412-8417.
[22]Adams L S, Phung S, Yee N, et al. Blueberry Phytochemicals Inhibit Growth and Metastatic Potential of MDA-MB-231 Breast Cancer Cells through Modulation of the Phosphatidylinositol 3-Kinase Pathway [J]. Cancer Research,2010,70(9):3594-3605.
[23]Yoon H, Liu R H. Effect of selected phytochemicals and apple extracts on NF-kappaB activation in human breast cancer MCF-7 cells [J]. Journal of Agriculture and Food Chemistry,2007,55(8): 3167-3173.
[24]Liu R H, Jacob J, Tennant B. Chemiluminescent detection of protein molecular weight markers in Western blot techniques [J]. Biotechniques,1997,22(4):594-595.
[19]Mosmann T. Rapid colorimetric assay for cellular growth and survival:Application to proliferation and cytotoxicity assays. Journal of Immunological Methods,1983,65(1-2),55-63.
[20]Felice D L, Sun J, Liu R H. A modified methylene blue assay for accurate cell counting [J]. Journal of Functional Foods,2009,1(1):109-118
[21]Yoon H, Liu R H. Effect of 2a-hydroxyursolic acid on NF-kB activation induced by TNF-a in human breast cancer MCF-7 cells [J]. Journal of Agriculture and Food Chemistry,2008,56(18): 8412-8417.
[22]Adams L S, Phung S, Yee N, et al. Blueberry Phytochemicals Inhibit Growth and Metastatic Potential of MDA-MB-231 Breast Cancer Cells through Modulation of the Phosphatidylinositol 3-Kinase Pathway [J]. Cancer Research,2010,70(9):3594-3605.
[23]Yoon H, Liu R H. Effect of selected phytochemicals and apple extracts on NF-kB activation in human breast cancer MCF-7 cells [J]. Journal of Agriculture and Food Chemistry,2007,55(8): 3167-3173.
[24]Liu R H, Jacob J, Tennant B. Chemiluminescent detection of protein molecular weight markers in Western blot techniques [J]. Biotechniques,1997,22(4):594-595.
[25]Daba A, Ezeronye O. Anti-cancer effect of polysaccharides isolated from higher basidiomycetes mushrooms [J]. African Journal of Biotechnology,2003,2(12):672-678.
[26]Frantz G. Polysaccharides in pharmacy:Current applications and future concepts [J]. Planta Medicine,1989,55:493-497.
[27]Wasser S P. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides [J]. Applied Microbiology and Biotechnology,2002,60:258-274.
[28]Zaidman B, Yassin M, Mahajna J, et al. Medicinal mushroom modulators of molecular targets as cancer therapeutics [J]. Applied Microbiology and Biotechnology,2005,67:453-468.
[29]Lee B, Bae J, Pyo H, et al. Biological activities of the polysaccharides produced from submerged culture of the edible basidiomycete Grifola frondosa [J]. Enzyme and Microbial Technology,2003, 32:574-581.
[30]Song G, Du Q. Isolation of a polysaccharide with anticancer activity from Auricularia polytricha using high-speed countercurrent chromatography with an aqueous two-phase system [J]. Journal of Chromatography A,2010,1217:5930-5934.
[31]Cui F, Tao W, Xu Z, et al. Structural analysis of antitumor heteropolysaccharide GFPSlb from the cultured mycelia of Grifola frondosa GF9801 [J]. Bioresource Technology,2007,98:395-401.
[32]Jin Y, Zhang L, Zhang M, et al. Antitumor activities of heteropolysaccharides of Poria cocos mycelia from different strains and culture media [J]. Carbohydrate Research,2003,338: 1517-1521.
[33]Li G, Kim D, Kim T, et al. Protein-bound polysaccharide from Phellinus linteus induces G2/M phase arrest and apoptosis in SW480 human colon cancer cells [J]. Cancer Letters,2004,216: 175-181.
[34]Zhang M, Cui S W, Cheung P C K, et al. Antitumor polysaccharides from mushrooms:a review on their isolation process, structural characteristics and antitumor activity [J]. Trends in Food Science & Technology,2007,18:4-19.
[35]Zou S, Zhang X, Yao W, et al. Structure characterization and hypoglycemic activity of a polysaccharide isolated from the fruit of Lycium barbarum L [J]. Carbohydrate Polymers,2010, 80:1161-1167.
[36]Wasser S P. Current findings, future trends, and unsolved problems in studies of medicinal mushrooms [J]. Applied Microbiology and Biotechnology,2011,89(5):1323-1332
[37]Soule H D, Maloney T M, Wolman S R, et al. Isolation and Characterization of a Spontaneously Immortalized Human Breast Epithelial-Cell Line, Mcf-10 [J]. Cancer Research,1990,50(18): 6075-6086.
[38]Sun J, Liu R H. Cranberry phytochemical extracts induce cell cycle arrest and apoptosis in human MCF-7 breast cancer cells [J]. Cancer Letters,2006,241(1):124-134.
[39]Sommers C L, Walkerjones D, Heckford S E, et al. Vimentin Rather Than Keratin Expression in Some Hormone-Independent Breast-Cancer Cell-Lines and in Oncogene-Transformed Mammary Epithelial-Cells [J]. Cancer Research,1989,49(15):4258-4263.
[40]Wasser S P. Medicinal mushrooms:ancient traditions, contemporary knowledge, and scientific enquiries [J]. International Journal for Medicinal Mushrooms,2007,9(3/4):187-189.
[41]Wasser S P. Medicinal mushroom science:history, current Status, future trends, and unsolved problems [J]. International Journal of Medicinal Mushrooms,2010,12(1):1-16.
[42]Hiyama H, Iavarone A, Reeves S A. Regulation of the cdk inhibitor p21 gene during cell cycle progression is under the control of the transcription factor E2F [J]. Oncogene,1998,16(12): 1513-1523
[43]Morris M C, Divita G. Characterization of the interactions between human cdc25C, cdks, cyclins and cdk-cyclin complexes [J]. Journal of Molecular Biology,1999,286(2):475-487
[44]Sun J, Liu R H. Cranberry phytochemical extracts induce cell cycle arrest and apoptosis in human MCF-7 breast cancer cells [J]. Cancer Letters,2006,241(1):124-134.
[45]Prakobwong S, Gupta S C, Kim J H, et al. Curcumin suppresses proliferation and induces apoptosis in human biliary cancer cells through modulation of multiple cell signaling pathways [J]. Carcinogenesis, 2011,32(9):1372-1380.
[46]Kim S P, Kang M Y, Choi Y H, et al. Mechanism of Hericium erinaceus (Yamabushitake) mushroom-induced apoptosis of U937 human monocytic leukemia cells [J]. Food & Function,2011, 2(6):348-356.
[1]Siegel R, Ward E, Brawley O, et al. Cancer statistics,2011:the impact of eliminating socioeconomic and racial disparities on premature cancer deaths [J]. CA Cancer J Clin,2011, 61(4):212-236
[2]Desantis C, Siegel R, Bandi P, et al. Breast cancer statistics,2011 [J]. CA Cancer J Clin,2011:
[3]Adams L S, Phung S, Yee N, et al. Blueberry phytochemicals inhibit growth and metastatic potential of MDA-MB-231 breast cancer cells through modulation of the phosphatidylinositol 3-Kinase pathway [J]. Cancer Research,2010,70(9):3594-3605
[4]Ray R B, Raychoudhuri A, Steele R, et al. Bitter melon (Momordica charantia) extract inhibits breast cancer cell proliferation by modulating cell cycle regulatory genes and promotes apoptosis [J]. Cancer Research,2010,70(5):1925-1931
[5]Prakobwong S, Gupta S C, Kim J H, et al. Curcumin suppresses proliferation and induces apoptosis in human biliary cancer cells through modulation of multiple cell signaling pathways [J]. Carcinogenesis,2011,32(9):1372-1380
[6]Eberhardt M V, Lee C Y, Liu R H. Nutrition-Antioxidant activity of fresh apples [J]. Nature, 2000,405(6789):903-904
[7]Chu Y F, Sun J, Wu X Z, et al. Antioxidant and anti proliferative activities of common vegetables [J]. Journal of Agricultural and Food Chemistry,2002,50(23):6910-6916
[8]Sun J, Chu Y F, Wu X Z, et al. Antioxidant and anti proliferative activities of common fruits [J]. Journal of Agricultural and Food Chemistry,2002,50(25):7449-7454
[9]Gan D, Ma L P, Jiang C X, et al. Production, preliminary characterization and antitumor activity in vitro of polysaccharides from the mycelium of Pholiota dinghuensis Bi [J]. Carbohydrate Polymers,2011,84(3):997-1003
[10]Wolfe K, Wu X Z, Liu R H. Antioxidant activity of apple peels [J]. Journal of Agricultural and Food Chemistry,2003,51(3):609-614
[11]Sun J, Liu R H. Cranberry phytochemical extracts induce cell cycle arrest and apoptosis in human MCF-7 breast cancer cells [J]. Cancer Letters,2006,241(1):124-134
[12]Liu J R, Dong H W, Chen B Q, et al. Fresh Apples suppress mammary carcinogenesis and proliferative activity and induce apoptosis in mammary tumors of the sprague-dawley rat [J]. Journal of Agricultural and Food Chemistry,2009,57(1):297-304
[13]Sliva D. Medicinal mushroom Phellinus linteus as an alternative cancer therapy (Review) [J]. Experimental and Therapeutic Medicine,2010,1(3):407-411
[14]Wasser S P. Medicinal mushroom science:history, current status, future trends, and unsolved problems [J]. International Journal of Medicinal Mushrooms,2010,12(1):1-16
[15]Luo J, Liu J, Sun Y, et al. Medium optimization, preliminary characterization and antioxidant activity in vivo of mycelial polysaccharide from Phellinus baumii Pilat [J]. Carbohydrate Polymers,2010,81(3):533-540
[16]Aida F M N A, Shuhaimi M, Yazid M, et al. Mushroom as a potential source of prebiotics:a review [J]. Trends in Food Science & Technology,2009,20(11-12):567-575
[17]Bera A K, Rana T R, T., Das S, et al. Mushroom lectin protects arsenic induced apoptosis in hepatocytes of rodents [J]. Human & Experimental Toxicology,2011,30(4):307-317
[18]Balogh G, Soares R, Meireles M, et al. Maitake (D fraction) mushroom extract induces apoptosis in breast cancer cells by BAK-1 gene activation [J]. Journal of Medicinal Food,2011, 14(6):563-572
[19]Mahajna J, Dotan N, Zaidman B Z, et al. Pharmacological values of medicinal mushrooms for prostate cancer therapy:the case of Ganoderma Lucidum [J]. Nutrition and Cancer-an International Journal,2009,61(1):16-26
[20]Chow L W C, Lo C S Y, Loo W T Y, et al. Polysaccharide peptide mediates apoptosis by up-regulating p21 gene and down-regulating cyclin D1 gene [J]. American Journal of Chinese Medicine,2003,31(1):1-9
[21]Zhang M, Chiu L C M, Cheung P C K, et al. Growth-inhibitory effects of a (3-glucan from the mycelium of Poria cocos on human breast carcinoma MCF-7 cells:Cell-cycle arrest and apoptosis induction [J]. Oncology Reports,2006,15(3):637-643
[22]Kim S P, Kang M Y, Kim J H, et al. Composition and mechanism of antitumor effects of Hericium erinaceus mushroom extracts in tumor-bearing mice [J]. Journal of Agricultural and Food Chemistry,2011,59(18):9861-9869
[23]Wasser S P. Current findings, future trends, and unsolved problems in studies of medicinal mushrooms [J]. Applied Microbiology and Biotechnology,2011,89(5):1323-1332
[24]Yoon H, Liu R H. Effect of selected phytochemicals and apple extracts on NF-kB activation in human breast cancer MCF-7 cells [J]. Journal of Agricultural and Food Chemistry,2007,55(8): 3167-3173
[25]Yoon H, Liu R H. Effect of 2 a-hydroxyursolic acid on NF-kB activation induced by TNF-a in human breast cancer MCF-7 cells [J]. Journal of Agricultural and Food Chemistry,2008,56(18): 8412-8417
[26]Liu R H, Jacob J, Tennant B. Chemiluminescent detection of protein molecular weight markers in Western blot techniques [J]. Biotechniques,1997,22(4):594-595
[27]Kawamura M, Kasai H. Delayed cell cycle progression and apoptosis induced by hemicellulase-treated Agaricus blazei [J]. Evidence-Based Complementary and Alternative Medicine,2007,4(1):83-94
[28]Huang G J, Deng J S, Huang S S, et al. Hispolon induces apoptosis and cell cycle arrest of human hepatocellular carcinoma Hep3B cells by modulating ERK phosphorylation [J]. Journal of Agricultural and Food Chemistry,2011,59(13):7104-7113
[29]Kim S P, Kang M Y, Choi Y H, et al. Mechanism of Hericium erinaceus (Yamabushitake) mushroom-induced apoptosis of U937 human monocytic leukemia cells [J]. Food & Function, 2011,2(6):348-356
[30]Hattori T S, Komatsu N, Shichijo S, et al. Protein-bound polysaccharide K induced apoptosis of the human Burkitt lymphoma cell line, Namalwa [J]. Biomedicine & Pharmacotherapy,2004, 58(4):226-230
[31]Kono K, Kawaguchi Y, Mizukami Y, et al. Protein-bound polysaccharide K partially prevents apoptosis of circulating T cells induced by anti-cancer drug S-l in patients with gastric cancer [J]. Oncology,2008,74(3-4):143-149
[32]Zhang M, Cui S W, Cheung P C K, et al. Polysaccharides from mushrooms:a review on their isolation process, structural characteristics and antitumor activity [J]. Trends in Food Science & Technology,2006,18(1):4-19
[33]Elmore S. Apoptosis:A review of programmed cell death [J]. Toxicologic Pathology,2007, 35(4):495-516
[34]Chipuk J E, Kuwana T, Bouchier-Hayes L, et al. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis [J]. Science,2004,303(5660): 1010-1014
[35]Buckley C D, Pilling D, Henriquez N V, et al. RGD peptides induce apoptosis by direct caspase-3 activation [J]. Nature,1999,397(6719):534-539
[36]Yin Y X, Liu Y X, Jin Y J, et al. PAC1 phosphatase is a transcription target of p53 in signalling apoptosis and growth suppression [J]. Nature,2003,422(6931):527-531
[37]Park J M, Greten F R, Li Z W, et al. Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition [J]. Science,2002,297(5589):2048-2051
[38]Cheung P C K, Zhang M, Chiu L C M, et al. Cell-cycle arrest and apoptosis induction in human breast carcinoma MCF-7 cells by carboxymethylated beta-glucan from the mushroom sclerotia of Pleurotus tuber-regium [J]. Carbohydrate Polymers,2006,66(4):455-462
[39]Ichijo H, Nishida E, Irie K, et al. Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways [J]. Science,1997,275(5296):90-94
[40]Fukuyo Y, Kitamura T, Inoue M, et al. Phosphorylation-dependent lys(63)-linked polyubiquitination of daxx is essential for sustained TNF-a-induced ASK1 activation [J]. Cancer Research,2009,69(19):7512-7517
[41]Hosokawa Y, Suzuki H, Suzuki Y, et al. Antiapoptotic function of apoptosis inhibitor 2-MALT1 fusion protein involved in t(11;18)(q21;q21) mucosa-associated lymphoid tissue lymphoma [J]. Cancer Research,2004,64(10):3452-3457
[42]Rangasamy V, Mishra R, Mehrotra S, et al. Estrogen suppresses MLK3-mediated apoptosis sensitivity in ER(+) breast cancer cells [J]. Cancer Research,2010,70(4):1731-1740
[43]Stoica G E, Franke T F, Moroni M, et al. Effect of estradiol on estrogen receptor-α gene expression and activity can be modulated by the ErbB2/PI 3-K/Akt pathway [J]. Oncogene, 2003,22(39):7998-8011
[44]Diaz-Cruz E S, Furth PA. Deregulated estrogen receptor a and p53 heterozygosity collaborate in the development of mammary hyperplasia [J]. Cancer Research,2010,70(10):3965-3974
[45]Thordarson G, Mendoza R A, Enriquez M I, et al. Interactions between IGF-I, estrogen receptor-a (ER a), and ER β in regulating growth/apoptosis of MCF-7 human breast cancer cells [J]. Journal of Endocrinology,2011,208(1):1-9
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |