丹皮酚、丹皮酚衍生物及其结构类似物的生物活性研究
|
摘要
丹皮酚（2-羟基-4-甲氧基苯乙酮）是传统中药丹皮的主要有效成分之一，具有广泛的生物活性，如抗菌消炎、镇痛、解热、镇静、催眠、抗肿瘤、抗过敏和预防心血管系统疾病等。本研究优化了提取和合成丹皮酚的方法，并对其主要的官能团进行修饰和改造，合成丹皮酚的衍生物以及结构类似物，通过对丹皮酚、丹皮酚衍生物以及结构类似物的生物活性（抗氧化、抑菌及抗病毒活性）进行对比研究，寻求结构与活性的关系。结果如下：
1.通过化学全合成的方法制备了2,4-二羟基苯乙酮、丹皮酚以及丹皮酚的4种结构类似物，并分别以丹皮酚和2,4-二羟基苯乙酮为结构模板合成了丹皮酚的衍生物及结构类似物共10种化合物，包括甲基化产物、酯化产物、苯氧乙酸类衍生物、烯丙基醚化产物以及Claisen重排产物、和氯乙酸反应的产物；丹皮酚侧链上的卤代产物以及羰基还原的产物。其中有4种化合物（4-甲氧基-2-烯丙基氧基苯乙酮、3-烯丙基-2-羟基-4-甲氧基苯乙酮、2-羟基-4-烯丙氧基苯乙酮和5-烯丙基-2,4-二羟基苯乙酮）是首次合成。
2.测试了丹皮酚、丹皮酚衍生物以及结构类似物共16种化合物的抗氧化活性（对羟基自由基·OH的清除能力、对超氧阴离子自由基O2-·清除能力、对DPPH·的清除能力、对小鼠的肝组织脂质过氧化的抑制作用），通过对比不同结构的化合物对自由基清除能力的差异，得到如下的结论：
（1）上述16种化合物所参与的四种抗氧化反应都和酚羟基的数目密切相关，酚羟基是此类分子具有抗氧化活性的必需官能团。分子中苯环上引入烯丙基能起到增强活性的作用。
（2）乙酰基也是在反应中起到重要作用的官能团，但不是必需官能团。乙酰基的存在显著降低了苯环上酚羟基清除·OH的活性，但是却显著增强了分子对O2-·自由基的清除能力。
（3）筛选得到5个具有广泛的较强活性的抗氧化化合物：16号（5-烯丙基-2,4-二羟基苯乙酮）、10号（3-烯丙基2-羟基-4-甲氧基苯乙酮）、1号（2,4-二羟基苯乙酮）、3号（2,5-二羟基苯乙酮）和14号（2-乙基-5-甲氧基苯酚）化合物。
3.以合成的起始化合物间苯二酚为对照样品，测试了丹皮酚、丹皮酚衍生物以及结构类似物共16种化合物对4种细菌（大肠杆菌、枯草杆菌、金黄葡萄球菌和蜡样芽胞杆菌）、10种病原真菌（白菜黑斑病菌HB、苹果腐烂病菌FL、黄瓜枯萎病菌HK、小麦赤霉病菌CM、小麦纹枯病菌WK、大葱紫斑病菌ZB、黄瓜灰霉病菌HM、葡萄炭疽病菌PTJ、棉花枯萎病菌MK、葡萄黑痘病菌PHD）的抑菌活性，通过分析合成过程中官能团引入或改变与化合物抑菌活性的关系，得到化学结构与生物活性之间的规律，结果表明：共有11种化合物具有较高的抑制细菌和真菌活性，其中10号、16号的作用尤其显著，在其0.5g/L的浓度下，上述4种细菌和10种病原真菌几乎无法生长。
分子中官能团结构对于化合物抑制细菌和抑制真菌的活性的影响既有相似性也有区别。其中相似点为：分子中的乙酰基结构对抑菌作用均有着非常的作用，可以大大提升抑菌能力；苯环上引入了烯丙基，相对应的抑菌能力会大幅度地提升，在引入的位置上，5位比3位更优；4-OH改变为甲氧基、烯丙氧基、乙氧基时，抑菌的活性变化不大。区别在于：同等浓度下，当2-OH变成烯丙氧基和乙酰氧基时，抑制细菌活性略有下降，但是抑制真菌的活性显著降低，甚至活性消失。
4.以丹皮酚、丹皮酚衍生物以及结构类似物中的16种化合物为供试材料，以极易感染烟草花叶病毒的烟草品种心叶烟为研究对象，初步筛选出具有高效抗TMV侵染活性的有效抗病毒结构，通过分析化合物结构与活性之间的构效关系，可以推测得到如下结论：
（1）酚类及其衍生物的分子中的酚羟基数目是影响此类化合物抗病毒活性的最重要的因素，且酚羟基数目越多，抗病毒活性越低。
（2）当2-OH变成酯键，会大大提高化合物的抗TMV病毒活性。
（3）当2-OH变成烯丙氧基乙酰氧基时，也会提高化合物的抗TMV病毒活性，但是效果不如乙酸酯显著。而分子中的乙酰基发生α-溴代或者4-甲氧基变成乙氧基，抗TMV病毒活性变化不显著，这说明这些不是影响抗TMV病毒活性的重要因素。
综上所述，在后续研究中设计合成具有更高抗氧化活性、抑菌活性和抗病毒活性的化合物时，可以根据上述结论，在分子中有目的性的引入官能团，进行分子结构的修饰改造。
Paeonol (2-hydroxy-4-methoxy acetophenone) is one of the main activeingredients of traditional Chinese medicine from the root barks of Paeonia Suffruticeosa Andr and the dried root and the entire plants of Pyenostelma Panicu latum(Bunge) K Schum, with a wide range of biological activities, such as anti-bacterialanti-inflammatory, analgesic, antipyretic, sedative, hypnotic, anti-tumor, anti-allergicand prevention of cardiovascular system diseases. In this study the methods ofextraction and synthesis of paeonol were optimized and the derivatives and structuralanalogues of paeonol were synthesized by modification and transformation of themain functional groups. The biological activities (antioxidant, antibacterial andantiviral activity) of Paeonol of paeonol derivatives and structural analogues werestudied comparatively to seek the relationship between structure and activities.Results are as follows:
1.2,4–Dihydroxyacetophenone, paeonol and its four structural analogues wereprepared by chemical synthesis,10derivatives and structural analogues weresynthesized with the structure of the paeonol and2,4-dihydroxyphenyl ethanone astemplates including methylated product, the esterification product, phenoxy aceticacid derivatives, allyl-etherified products and the Claisen rearrangement product, thereaction product with richloroacetic acid, halogenated product on the side chain ofpaeonol and the reduction product of the carbonyl group. Among them there are fourkinds of compound (4-methoxy-2-allyloxy-acetophenone,3-allyl-2-hydroxy-4-methoxy-acetophenone,2-hydroxy-4-allyloxyacetophenone and5-allyl-2,4-dihydroxyphenyl ethyl ketone) were first synthesized.
2. The antioxidant activity (scavenging of hydroxyl radical (OH), superoxideanion radical (O2-), scavenging DPPH, scavenging capacity of mouse liver tissuelipid peroxidation) of16compounds including paeonol, derivatives and structuralanalogues of paeonol were tested. The conclusions were obtained as follows bycomparing the different structures of the compounds and the difference scavenging abilities on the free radicals:
(1) The participation of the four anti-oxidation reactions of the above-mentioned16kinds of compounds had close relationship with the number of phenolic hydroxylgroup, which showed that the phenolic hydroxyl group is the necessary functionalgroup among these kinds of molecules having anti-oxidation activites. Theintroduction of an allyl group on the benzene rings in the molecule can play the roleof enhanced activity.
(2) An acetyl group also played an important role in the reaction, but it is notnecessary for the functional group. The presence of an acetyl group on the benzenering significantly reduced the activity of clearing OH, but significantly enhanced theactivity of scavenging O2-radical.
(3) Five compounds with a wide range of strong antioxidant activities were confirmedby screening, including No.16(5-allyl-2,4-di-hydroxyacetophenone), No.10(3-allyl-2-hydroxy-4-methoxy compoundsacetophenone), No.1(2,4-di-hydroxyacetophenone), No.3(2,5-di-hydroxyacetophenone) and No.14(2-ethyl-5-methoxy-phenol).
3. The antibacterial activities on four kinds of bacteria and10kinds ofpathogenic fungi of16compounds including paeonol, derivatives and structuralanalogues of paeonol were tested, with resorcinol (the synthesis starting compounds)as the control samples. The conclusions were obtained as follows by comparing thedifferent structures of the compounds and the difference antibacterial activities on thebacteria and pathogenic fungi.
There are11kinds of compounds having higher inhibition activities on bacterialand fungi, wherein No.10and No.16had especially significant activities. With thepresence of them at the concentration of0.5g/L, the above-mentioned four kinds ofbacteria, and10kinds of pathogenic fungi growed almost impossiblely.
There are similarities and differences of the functional group to inhibit bacteriaand to inhibit the fungi. Similarities: Acetyl group in the molecules played a veryimportant role in the inhibitory effects, which can greatly enhance the antibacterialactivity; The allyl group introduced on the benzene ring can greatly enhance the corresponding inhibitory capacity, the5position is better than the3position as it isintroduced. When4-OH was changed to methoxy, allyloxy, ethoxy, the antibacterialactivities were not changed greatly. Differences: when the2-OH was changed toallyloxy group and an acetyl group, the antibacterial activities had a slight decrease,but antifungal activities were significantly reduced, even disappeared at the sameconcentration.
4. The16compounds of paeonol, paeonol derivatives and structural analogueswere tested as materials, the heart leaf tobacco which were easily infected with thetobacco mosaic virus tobacco varieties were studied as the research object; weobtained the structure with highly anti-viral activity by initial screening. Through theanalysis of the structure-activity relationship, the conclusions can be speculated asfollows:
(1) The most important factor which affect the antiviral activities of such compoundswas the number of phenolic hydroxyl groups in the molecule, with the more numberof phenolic hydroxyl group leading to lower antiviral activities.
(2) When2-phenolic hydroxyl group was changed into acetate, the resistance activityof compounds to TMV virus will be greatly enhanced.
(3) When the2-hydroxyl group of the phenol was changed into allyloxy-acetoxy, theanti-TMV virus activity of the compound will be improved, but the effect was lessthan that of acetate significantly. When the acetyl group in the molecule occurs as theα-bromo or the4-methoxy occurs as4-ethoxy, the anti-TMV virus activity did notchange significantly, which indicatied that these were not the important factors toaffect the anti-TMV virus activity.
In summary, if the compounds having higher antioxidant activities, antibacterialactivities and antiviral activities were designed and synthesized in the subsequentstudy, the introduction of active functional group, the modification and transformationof the molecular structure can be obtained according to the above conclusions.
1.通过化学全合成的方法制备了2,4-二羟基苯乙酮、丹皮酚以及丹皮酚的4种结构类似物，并分别以丹皮酚和2,4-二羟基苯乙酮为结构模板合成了丹皮酚的衍生物及结构类似物共10种化合物，包括甲基化产物、酯化产物、苯氧乙酸类衍生物、烯丙基醚化产物以及Claisen重排产物、和氯乙酸反应的产物；丹皮酚侧链上的卤代产物以及羰基还原的产物。其中有4种化合物（4-甲氧基-2-烯丙基氧基苯乙酮、3-烯丙基-2-羟基-4-甲氧基苯乙酮、2-羟基-4-烯丙氧基苯乙酮和5-烯丙基-2,4-二羟基苯乙酮）是首次合成。
2.测试了丹皮酚、丹皮酚衍生物以及结构类似物共16种化合物的抗氧化活性（对羟基自由基·OH的清除能力、对超氧阴离子自由基O2-·清除能力、对DPPH·的清除能力、对小鼠的肝组织脂质过氧化的抑制作用），通过对比不同结构的化合物对自由基清除能力的差异，得到如下的结论：
（1）上述16种化合物所参与的四种抗氧化反应都和酚羟基的数目密切相关，酚羟基是此类分子具有抗氧化活性的必需官能团。分子中苯环上引入烯丙基能起到增强活性的作用。
（2）乙酰基也是在反应中起到重要作用的官能团，但不是必需官能团。乙酰基的存在显著降低了苯环上酚羟基清除·OH的活性，但是却显著增强了分子对O2-·自由基的清除能力。
（3）筛选得到5个具有广泛的较强活性的抗氧化化合物：16号（5-烯丙基-2,4-二羟基苯乙酮）、10号（3-烯丙基2-羟基-4-甲氧基苯乙酮）、1号（2,4-二羟基苯乙酮）、3号（2,5-二羟基苯乙酮）和14号（2-乙基-5-甲氧基苯酚）化合物。
3.以合成的起始化合物间苯二酚为对照样品，测试了丹皮酚、丹皮酚衍生物以及结构类似物共16种化合物对4种细菌（大肠杆菌、枯草杆菌、金黄葡萄球菌和蜡样芽胞杆菌）、10种病原真菌（白菜黑斑病菌HB、苹果腐烂病菌FL、黄瓜枯萎病菌HK、小麦赤霉病菌CM、小麦纹枯病菌WK、大葱紫斑病菌ZB、黄瓜灰霉病菌HM、葡萄炭疽病菌PTJ、棉花枯萎病菌MK、葡萄黑痘病菌PHD）的抑菌活性，通过分析合成过程中官能团引入或改变与化合物抑菌活性的关系，得到化学结构与生物活性之间的规律，结果表明：共有11种化合物具有较高的抑制细菌和真菌活性，其中10号、16号的作用尤其显著，在其0.5g/L的浓度下，上述4种细菌和10种病原真菌几乎无法生长。
分子中官能团结构对于化合物抑制细菌和抑制真菌的活性的影响既有相似性也有区别。其中相似点为：分子中的乙酰基结构对抑菌作用均有着非常的作用，可以大大提升抑菌能力；苯环上引入了烯丙基，相对应的抑菌能力会大幅度地提升，在引入的位置上，5位比3位更优；4-OH改变为甲氧基、烯丙氧基、乙氧基时，抑菌的活性变化不大。区别在于：同等浓度下，当2-OH变成烯丙氧基和乙酰氧基时，抑制细菌活性略有下降，但是抑制真菌的活性显著降低，甚至活性消失。
4.以丹皮酚、丹皮酚衍生物以及结构类似物中的16种化合物为供试材料，以极易感染烟草花叶病毒的烟草品种心叶烟为研究对象，初步筛选出具有高效抗TMV侵染活性的有效抗病毒结构，通过分析化合物结构与活性之间的构效关系，可以推测得到如下结论：
（1）酚类及其衍生物的分子中的酚羟基数目是影响此类化合物抗病毒活性的最重要的因素，且酚羟基数目越多，抗病毒活性越低。
（2）当2-OH变成酯键，会大大提高化合物的抗TMV病毒活性。
（3）当2-OH变成烯丙氧基乙酰氧基时，也会提高化合物的抗TMV病毒活性，但是效果不如乙酸酯显著。而分子中的乙酰基发生α-溴代或者4-甲氧基变成乙氧基，抗TMV病毒活性变化不显著，这说明这些不是影响抗TMV病毒活性的重要因素。
综上所述，在后续研究中设计合成具有更高抗氧化活性、抑菌活性和抗病毒活性的化合物时，可以根据上述结论，在分子中有目的性的引入官能团，进行分子结构的修饰改造。
Paeonol (2-hydroxy-4-methoxy acetophenone) is one of the main activeingredients of traditional Chinese medicine from the root barks of Paeonia Suffruticeosa Andr and the dried root and the entire plants of Pyenostelma Panicu latum(Bunge) K Schum, with a wide range of biological activities, such as anti-bacterialanti-inflammatory, analgesic, antipyretic, sedative, hypnotic, anti-tumor, anti-allergicand prevention of cardiovascular system diseases. In this study the methods ofextraction and synthesis of paeonol were optimized and the derivatives and structuralanalogues of paeonol were synthesized by modification and transformation of themain functional groups. The biological activities (antioxidant, antibacterial andantiviral activity) of Paeonol of paeonol derivatives and structural analogues werestudied comparatively to seek the relationship between structure and activities.Results are as follows:
1.2,4–Dihydroxyacetophenone, paeonol and its four structural analogues wereprepared by chemical synthesis,10derivatives and structural analogues weresynthesized with the structure of the paeonol and2,4-dihydroxyphenyl ethanone astemplates including methylated product, the esterification product, phenoxy aceticacid derivatives, allyl-etherified products and the Claisen rearrangement product, thereaction product with richloroacetic acid, halogenated product on the side chain ofpaeonol and the reduction product of the carbonyl group. Among them there are fourkinds of compound (4-methoxy-2-allyloxy-acetophenone,3-allyl-2-hydroxy-4-methoxy-acetophenone,2-hydroxy-4-allyloxyacetophenone and5-allyl-2,4-dihydroxyphenyl ethyl ketone) were first synthesized.
2. The antioxidant activity (scavenging of hydroxyl radical (OH), superoxideanion radical (O2-), scavenging DPPH, scavenging capacity of mouse liver tissuelipid peroxidation) of16compounds including paeonol, derivatives and structuralanalogues of paeonol were tested. The conclusions were obtained as follows bycomparing the different structures of the compounds and the difference scavenging abilities on the free radicals:
(1) The participation of the four anti-oxidation reactions of the above-mentioned16kinds of compounds had close relationship with the number of phenolic hydroxylgroup, which showed that the phenolic hydroxyl group is the necessary functionalgroup among these kinds of molecules having anti-oxidation activites. Theintroduction of an allyl group on the benzene rings in the molecule can play the roleof enhanced activity.
(2) An acetyl group also played an important role in the reaction, but it is notnecessary for the functional group. The presence of an acetyl group on the benzenering significantly reduced the activity of clearing OH, but significantly enhanced theactivity of scavenging O2-radical.
(3) Five compounds with a wide range of strong antioxidant activities were confirmedby screening, including No.16(5-allyl-2,4-di-hydroxyacetophenone), No.10(3-allyl-2-hydroxy-4-methoxy compoundsacetophenone), No.1(2,4-di-hydroxyacetophenone), No.3(2,5-di-hydroxyacetophenone) and No.14(2-ethyl-5-methoxy-phenol).
3. The antibacterial activities on four kinds of bacteria and10kinds ofpathogenic fungi of16compounds including paeonol, derivatives and structuralanalogues of paeonol were tested, with resorcinol (the synthesis starting compounds)as the control samples. The conclusions were obtained as follows by comparing thedifferent structures of the compounds and the difference antibacterial activities on thebacteria and pathogenic fungi.
There are11kinds of compounds having higher inhibition activities on bacterialand fungi, wherein No.10and No.16had especially significant activities. With thepresence of them at the concentration of0.5g/L, the above-mentioned four kinds ofbacteria, and10kinds of pathogenic fungi growed almost impossiblely.
There are similarities and differences of the functional group to inhibit bacteriaand to inhibit the fungi. Similarities: Acetyl group in the molecules played a veryimportant role in the inhibitory effects, which can greatly enhance the antibacterialactivity; The allyl group introduced on the benzene ring can greatly enhance the corresponding inhibitory capacity, the5position is better than the3position as it isintroduced. When4-OH was changed to methoxy, allyloxy, ethoxy, the antibacterialactivities were not changed greatly. Differences: when the2-OH was changed toallyloxy group and an acetyl group, the antibacterial activities had a slight decrease,but antifungal activities were significantly reduced, even disappeared at the sameconcentration.
4. The16compounds of paeonol, paeonol derivatives and structural analogueswere tested as materials, the heart leaf tobacco which were easily infected with thetobacco mosaic virus tobacco varieties were studied as the research object; weobtained the structure with highly anti-viral activity by initial screening. Through theanalysis of the structure-activity relationship, the conclusions can be speculated asfollows:
(1) The most important factor which affect the antiviral activities of such compoundswas the number of phenolic hydroxyl groups in the molecule, with the more numberof phenolic hydroxyl group leading to lower antiviral activities.
(2) When2-phenolic hydroxyl group was changed into acetate, the resistance activityof compounds to TMV virus will be greatly enhanced.
(3) When the2-hydroxyl group of the phenol was changed into allyloxy-acetoxy, theanti-TMV virus activity of the compound will be improved, but the effect was lessthan that of acetate significantly. When the acetyl group in the molecule occurs as theα-bromo or the4-methoxy occurs as4-ethoxy, the anti-TMV virus activity did notchange significantly, which indicatied that these were not the important factors toaffect the anti-TMV virus activity.
In summary, if the compounds having higher antioxidant activities, antibacterialactivities and antiviral activities were designed and synthesized in the subsequentstudy, the introduction of active functional group, the modification and transformationof the molecular structure can be obtained according to the above conclusions.
引文
[1]中国药典[M].一部.2005：119.
[2]王本祥.现代中药药理与临床[M].天津：天津科技翻译出版社,2004:740.
[3]严永清.中药辞海[M].第2卷.北京:中国医药科技出版社,1996:282-285.
[4]宋丽明摘译，江纪武校.牡丹皮中2种单萜的立体结构及自由基清除作用[J].国外医学中医中药分册，2002，24(l):29-30.
[5] Yoshikawa M, Ohata T, Kawaguchi A, et al. Bioactive constituents of Chinese naturalmedicines. V. Radical scavenging effect of Moutan Cortex.(l): Absolute stereostructures oftwo monoterpenes，paeonisuffrone and paeonisuffral [J]. Chem Pharm Bull(Tokyo)，2000，48(9):1327-1331.
[6]李方军.牡丹皮化学成分及药理作用研究进展[J].安徽医药，2004，8(1):9-10.
[7]宋丽明摘译,江纪武校.牡丹皮中牡丹苷A～E和没食子酰羟基芍药苷的结构及自由基清除作用[J].国外医学中医中药分册，2002,24(l):30-31.
[8] Yashikawa M, Uchida E，Kawaguchi A, et al. Galloyl-oxypaeoniflorin,suffruticosides A,B,C,and D, five new antioxidative glycosides and suffruticoside E, A paeonol glycoside，fromChinese Moutan Cortex[J].Chem Pharm Bull(Tokyo),1992,40(8):2248-2250.
[9] Matsuda H, Ohata T, Kawaguchi A, et al. Bioactive constituents of Chinese natural medicines.VI. Moutan Cortex.(2): structures and radical scavenging effects of suffruticosides A, B, C, D,and E and galloyl-oxypaeoniflorin.[J].Chem Pharm Bull,200l,49(l):69-72.
[10]陈悦娇,陈杰林,马应丹.丹皮挥发油化学成分的GC-MS分析[J].广州食品工业科技,2002,18(4):36-37.
[11]吴少华,马云保,罗晓东,等.丹皮的化学成分研究[J].中草药，2002，33(8):679-680.
[12] Lin HC, Ding HY, Wu YC. Two novel compounds from Paeonia suffruticosa [J].J Nat Prod,1998,61(3):343-346.
[13]刘春生,王海等.药用动植物种养加工技术·牡丹皮[M].北京:中国中医药出版社,2001:57-61.
[14]成都中医学院.中药鉴定学[M].上海:上海科技出版社,1980:239-241.
[15]张艳,范俊安.中药材牡丹皮研究概况III丹皮化学成分研究概况[J].重庆中草药研究,2008,12(2):24-29.
[16]房杏春，安登魁，董善事，等。HPLC法测定丹皮中丹皮酚含量[J].中国药科大学学报,1989,20(2):109-111.
[17]刘放,黄卫平.HPLC法测定牡丹皮及其制剂中丹皮酚含量[J].基层中药杂志,1997,11(1):34-36.
[18]章灵华,肖培根,黄艺,等.丹皮酚的药理与临床研究进展[J].中国中西医结合杂志,1996,16(3):187-189.
[19]袁金伟,屈凌波,白云亮,等。丹皮酚结构改造研究进展[J].河南工业大学学报,2011,32(2):88-93.
[20]龚明贵,张巧明,秦翠丽等.牡丹中丹皮酚含量及其提取检测方法研究[J].时珍国医国药,2007,18(3):709-711.
[21]张云升,成晓迅,和健等.牡丹皮中丹皮酚的提取工艺研究[J].河北省科学院学报,2005,22(3):49-51.
[22]方岩雄,黄剑明,张昆.用超临界CO2从丹皮中提取丹皮酚[J].精细化工，2001,18(4):201-205.
[23]王立红,周丽莉,雷雪等.超临界CO2萃取徐长卿中丹皮酚的工艺[J].沈阳药科学报,2006,23(1):53-56.
[24]李玉贤,万炎,陈晓岚等.牡丹皮中丹皮酚的提取方法研究[J].河南中医学院学报，2007,22(2):37-38.
[25]卞凌.徐长卿中丹皮酚水蒸气蒸馏法提取工艺研究[J].海峡学,2005,17(6):35-36).
[26]彭玲,李成网,张洁.蒸馏法提取丹皮中丹皮酚的工艺研究[J].安徽医药,2012,16(4):446-447.
[27]陈巧谋,陈平,王炜,等.复方延胡索片中丹皮酚β-环糊精包合物的制备研究[J].湖南中医药导报,2003,9(8):53.
[28]刘庆发,韩玉玲.正交设计法探讨牡丹皮中丹皮酚的提取工艺[J].黑龙江医药,2002,15(5):351-352.
[29]李利红,张晓静.正交试验法优选丹皮酚提取工艺[J].安徽农业科学,2008,36(14):5707
[30] Li H, Chen B, Nie L et al. Solvent Effects on Focused Microwave Assisted Extraction ofPolyphenolic Acids from Eucommia Ulmodies [J].Phytochem.Anal.,2004,15(5):306-312.
[31]宫静静,王娟,沈平孃.微波辅助萃取技术在不同药用部位的工艺研究[J].中国中药杂志,2007,32(16):1641-1643.
[32] Ye Q, Deng C H. Determination of Camphor and Borneol in Traditional Chinese Medicinesby Microwave-Assisted Extraction and Gas Chromatography with Flame IonizationDetector[J].Analytical Letters,2008,41(13):2387-2401.
[33]叶青,郑大贵.微波辅助萃取水蒸气蒸馏技术在中药有效成分分析中的应用研究[J].光谱实验室,2010,27(3):1077-1079.
[34]陈江斌，唐其柱，黄从新等.丹皮酚对心肌细胞自律性和延迟后除极的影响[J]．中国应用生理学杂志，1999，15(4)：332-334．
[35]孙言才,沈玉先，孙国平.丹皮酚的主要药理活性研究进展[J].中成药，2004，26（7）：579-582.
[36] Li L J，Zhong Z H,Chen Q．Fetal Determination of paeonol by a flow injection chemi luminessence method[J]．Chem Res Appl，2006，18(7)：886-888．
[37]严永庆，余传隆，黄泰康等主编．中药辞海(第二卷)[M]．第1版．北京：中国医药科技出版社，1996，282-287．
[38]李薇，王运亮，蔡绍皙等．丹皮酚和阿司匹林对大鼠血液流变性影响的比较[J]．中草药，2000，31(1)：29-31．
[39]胡大一.贯彻循证医学的原则，重视动脉粥样硬化的预防[J].中华心血管病杂志，2002;9(30):513-514.
[40] Ross R.The pathogenesis of atherosclerosis: a perspective for the1990s[J].Nature，1993，362:801-809.
[41]石琳，范盘生，方几希.丹皮酚对兔实验性动脉粥样硬化及血小板的抑制作用[J].中国药理学报，1988,9(6):555-558.
[42]戴敏，警晓梅，彭代银，等.丹皮酚抗鹤鹑试验性动脉粥样硬化作用[J].中国中药杂志，1999,24(8):488-490，512.
[43]戴敏，刘青云，顾承刚，等.丹皮酚对脂质过氧化反应及低密度脂蛋白氧化修饰的抑制作用[J].中国中医杂志，2000,25(10):625-627.
[44]范盘生.丹皮酚抑制培养主动脉平滑肌细胞的增殖及抗自由基作用[J].中药药理与临床,1991,7(3):13-16.
[45]苗耀诚.抗动脉粥样硬化药物研究进展[J].国外医学药学分册，1995;22(5):257
[46]陈宇，王志武，范洪学.动脉粥样硬化发生相关因素研究现状和展望[J].国外医学.老年医学分册，1999;20(4):145.
[47] Esper RJ, Vilarino JO,Maehado RA,et al. Endothelial dysfunction in normal and abnormalglucose metabolism[J]. Adv Cardiol,2008,45:17-43.
[48]刘瑾.丹皮酚干预兔实验性动脉粥样硬化的实验研究[D].山东医科大学硕士学位论文.2006.
[49]李逢春,周晓玲,磨红玲等．丹皮酚注射增强免疫功能的实验研究[J]．中国中西医结合杂志，1994，14(1)：37—38．
[50]朱作金,蔡福盛,杨志平等．丹皮酚雾化吸人对大鼠免疫功能的影响[J]．广西医科大学学报，1994，11(4)：386—387．
[51]侯福生，鲍学平.葫芦素B及牡丹酚对苯并(a)花在大鼠肝微粒体代谢的影响[J].中草药,1985,16(3):25-26.
[52] Chang HL，Hung CF，Yeh CC, et al. Paeonol promoted2-aminofluorene and p-aminobenzoicacid acetylations by mononuclear leucocytes from Sprague-Dawley rats. Cytobios，2000,103(404):149-158.
[53] Chung JG. Paeonol Promotion of DNA adducts formation and arylamines N-acetyltransferaseactivity in human colon tumor cells. Food-Chem-Toxicol.1999,37(4):327-334.
[54]孙慧君，王晓琦，于丽敏，等.丹皮酚对MDR逆转作用的研究.解剖科学进展，2000，6(1):59-61.
[55]孙国平,沈玉先,张玲玲，等.丹皮酚的体内外抗肿瘤作用.安徽医科大学学报,2002,37(3):183-185.
[56]孙国平，王华．丹皮酚诱导K-（562)细胞凋亡的研究[J]．中国药理学通报,2004,20(5)：550～552．
[57]孙国平，沈玉先，张玲玲，等.丹皮酚对HepA荷瘤小鼠免疫调节和抑瘤作用研究.中国药理学通报,2003,19(2):160-162.
[58]胡映辉,林志彬,何云庆等.灵芝菌丝体多糖通过增强小鼠巨噬细胞功能诱导HL-60细胞凋亡[J].中国药理学通报,1999,15(1):27-30.
[59] Nishmura T, Ohta S,Sato N et al. Combination tumor immunotherapy with recombinationtumor necrosis factor and recombinant interleukin2in mice. Int J Cancer,1987,40(2):255-261.
[60]葛焕琦,李乐复,王丽英,等.白细胞介素II增强肿瘤坏死因子对人肝癌细胞的细胞毒性作用.白求恩医科大学学报,1997,23(5):779-781.
[61] Vasiliki P，Prokopios Mloanna C，et a1．Volatiles with antimicmbial activity from the rootsof Greek Paeonia taxa[J]．J Ethno pharmacol，2002，8l(1)：101．
[62]杜凡,李惠芬,王宇歆,等.牡丹皮中丹皮酚、总苷、多糖单用及合用后的协同抑菌作用考查[J].天津药学,2008,20(2):10-12.
[63]文洪林,桂红,贺红.丹皮、白芍对牙龈卟啉单胞菌、具核梭杆菌的体外抑菌活性研究[J].临床和实验医学杂志.2012,11(18):1469.
[64]吴晓慧,吴国荣,张卫明,等.丹皮酚提取、磺化及对植物病原菌的抑菌试验[J].中药材,2003,26(11):778-780.
[65]李骅,王四旺,张邦乐.丹皮酚的药理活性和药物动力学研究进展[J].亚太传统医药.2010,6(2):110-112.
[66]唐景荣,石琳.丹皮酚对体外培养乳鼠心肌细胞45Ca摄取的影响[J].中国药理学与毒理学杂志,1991,5(2):108-109.
[67]唐景荣,石琳.丹皮酚对钙反常培养心肌细胞的保护作用[J].中国中药杂志,1991,16(9):557-560.
[68]唐景荣,石琳.丹皮酚磺酸钠对钙反常培养乳鼠心肌细胞Ca2+内流的抑制作用[J].药学学报,1991,26(3):161-165.
[69]刘国坤,谢联辉,林奇英,等.15种植物的单宁提取物对烟草花叶病毒(TMV)的抑制作用[J].植物病理学报.2003,33(3):279-283.
[70] Kovendi A, Beu D L, Gagiu F, et al. Resacetophenone [J]. Rom,1973,53:277.
[71] Mam R, Venkataraman K. The preparation of phenolic ketones and chalcones by means ofboron trifluoride [J]. Current Sci (India),1954,23:220-221.
[72]唐海燕、杨石、王见宾,等.丹皮酚制备工艺、剂型改革及临床应用概述.江苏中医药.2004,4:58-60.
[73]程杰,方志杰,姜宇华,等.丹皮酚的新法制备及其糖苷化衍生物的合成[J].化学研究与应用,2009,21(10),1469-1472.
[74] Windscheif P.M., Vogtle E.F. Sustituted dipyridyenes a dethynes all key pyridine buildingblokes [J].Synthesis,1994,(1):87-92.
[75]孟庆华,冀亚飞,张雁秋.丹皮酚的提取及其衍生物的合成.徐州师范大学学报.1998,16(2):41-43.
[76]潘显道,费勤志,朱承根,等.5个丹皮酚酯的合成和体外抗肿瘤活性研究.安徽医药.2004,8(1):16-18.
[77] Li W., Koike K., Asada Y. et al. Biotransformation of Paeonol by Panax ginseng root andcell cultures [J]. Journal of Molecular Catalysis Enzymatic,2005,35:117-121.
[78]程杰,方志杰,姜宇华,等.丹皮酚的新法制备及其糖苷化衍生物的合成[J].化学研究与应用,2009,21(10):1469-1472.
[79]汪显阳.正交设计法优化Peonoxyacetic Acid的合成[J].数理医药学志,2000,13(4):344-345.
[80]胡桂.丹皮酚磺酸钠制备的研究[J1.中国医院药学杂志,2004,24(5):319.
[81]李如法.以丹皮酚为母体合成的丙醇胺类醚化合物及其衍生物[P].中国专利:CN03135253.7,2004-07-21.
[82]李如法.以丹皮酚为母体合成的丙醇胺类醚化合物及其衍生物[P].中国专利:CN03135254.5,2004-07-21.
[83]祁俊生,曹阳,王远亮.丹皮酚的选择性溴化反应[J].应用化学,2003,20(7):702-703.
[84] Dey DK, Dey SP, Elmali A, et al. Crystal structure and conformation of2-{(2’-aminobenzyl)iminoethyl}-5-methoxyphenol [J]. Chemical Sciences,2001,56(4/5):375-380.
[85]朱海生.丹皮酚Schiff碱与氨基磷酸酯衍生物的合成研究[D].2011,郑州大学硕士学位论文.
[86]王学军,刘建利,王江凯.丹皮酚衍生物的合成及其抗肿瘤细胞增殖研究[J].药学学报,2012,47(1):72-76.
[87]姚日生,李发,邓胜松,等.丹皮酚单硝化与二硝化衍生物的合成[J].合肥工业大学学报,2009,32(2):177-180.
[88]曹阳,罗琦,祁俊生,等.2-羟基-4-甲氧基-5-胂酸基苯乙酮的合成[J].重庆三峡学院学报,2003,19(2):125-126.
[89] Patel VK, Vasanwala AM, Jejurkar CR. Synthesis of mixed Schiff base complexes of copper(II) and nickel (II) and their spectral, magnetic and antifungal studies [J]. India J Chem SectA,1989,28a (8):719-721.
[90] XU T-T, XU X-Y, GAO J, et al. Synthesis, Structure and Antimicrobial study ofN-Salicylidene-Phenylpropanolamine Bicopper (II) Complex [J]. Synthesis and Reactivity inInorganic, Metal-Organic and Nano-Metal Chemistry,2006,36:667-672.
[91] XU T-T, XU X-Y, GAO J, et al. Crystal and Molecular Structure of two new Schiff bases:paeonol-ethylenediamine and paeonol-1,3-propylenediamine [J]. Journal of StructureChemistry (Russia),2007,48(1):C161-165.
[92]石鑫.丹皮酚三氮唑衍生物的合成及工艺研究[D].河南师范大学硕士学位论文,2012.
[93]王铮，任天池，乔淑珍.丹皮酚-β-环糊精包合物的研究[J].中国药学杂志,1989,24(7):4102-4104.
[94]王江恺.丹皮酚及其衍生物的合成与抗肿瘤活性研究[D].西北大学硕士论文,2010.
[95]曹阳.丹皮酚胂化合物诱导肝癌细胞HepG2凋亡及分子机制探讨[D].重庆大学硕士学位论文,2004.
[96]杜君.丹皮酚磺酸钠注射液穴位注射治疗颈椎病60例临床观察[J].医学信息,2007,20(10):1855-1856.
[97]朱越.丹皮酚磺酸钠注射液治疗中枢性高热临床观察.实用医技杂志,2008,15(3):333-334.
[98]胡丽娟.丹皮酚磺酸钠注射液与利多卡因合用减轻肌内疼痛的临床观察.医学信息,2007,20(11):1999-2000.
[99]谌曦,黄传兵,张皖东,等.四妙散加减合丹皮酚磺酸钠治疗急性痛风性关节炎临床研究[J].中国中医药信息杂志,2011,18(4):66-67.
[100]李永忻.丹皮酚磺酸钠注射液促进骨折愈合的疗效观察.实用药物与临床.2007,10(4):220-221.
[101]吴晓慧,吴国荣,张卫明,等.丹皮酚及其磺化物体外抗氧化作用[J].南京师大学报(自然科学版),2005,28(3):83-85.
[102]沈奇,金春雁,缪月秋,等.丹皮酚磺酸钠对樱桃番茄的保鲜作用的研究[J].食品科学,2005,26(4):256-259.
[103]吴婷,沈奇,吴晓慧,等.丹皮酚及其磺化物对樱桃番茄果实的保鲜作用比较研究[J].食品科学,2007,28(2),330-334.
[104]常福辰,吴国荣,吴晓慧,等.丹皮酚磺酸钠对蒌蒿的保鲜作用.南京师大学报(自然科学版),2005,28(2):88-91.
[105] XU T-T, XU X-Y, GAO J, et al. Synthesis, Structure and Antimicrobial study ofN-Salicylidene-Phenylpropanolamine Bicopper (II) Complex [J]. Synthesis and Reactivityin Inorganic, Metal-Organic and Nano-Metal Chemistry,2006,36:667-672.
[106]许同桃.丹皮酚金属配合物的合成及生物活性研究.时珍国医国药.2009,20(4):917-919.
[107]高健,相海鹰,许同桃,等。丹皮酚及其席夫碱衍生物的抑菌性研究.化学试剂,2007,29(1):59-60.
[108]于曙光,郑国生,潘大仁.丹皮酚合成过程中抑菌活性的变化研究.化学与生物工程,2012,29(8):56-58.
[109] FRENETTE R, GAUTHIER J Y, YOUNG R N, et al. Stereo selective synthesis ofleukotriene antagonists: US,4857659[P].1989-08-15.
[110]林宝玉.浅谈自由基对人体的危害及清除方法.中国西部科技[J].2007(18).
[111]熊双丽，李安林，金征宇.猪喉软骨硫酸软骨素体外超氧阴离子自由基清除机理探讨［J］.食品科学.2008，29(2):362-365.
[112]杨保收，陈越，金久善等.氧自由基检测方法在生物学和医学中的应用［J］.动物科学与动物医学.1999，7，(16):17-18.
[113]范秀萍，吴红棉，王娅楠等.4种贝类糖胺聚糖体外清除自由基活性的比较［J］.食品科技.2008，2(33):165-167.
[114］彭长连，陈少薇，林植芳，等.用有机自由基DPPH·法评价植物抗氧化能力［J］.生物化学与生物物理进展，2000，27(6):658-661.
[115]郑晶泉.抗氧化剂抗氧化实验研究进展.国外医学卫生学分册[J].2000，27(l):55-56.
[116]徐清萍,敖宗华,陶文沂.恒顺香醋DPPH·自由基清除活性成分的研究[J].中国调味品,2004(7):19-23.
[117]郑建仙.功能性食品[M].北京:中国轻工出版社,1995.344-378.
[118] WINKLHOFER Roob BM,ELLEMUNTERH,FRUHWIRTHM,et al. Plasma vitamin Cconcentrations in patients with cystic fibrosis: evidence of associations with lunginflammation [J]. American Journal of Clinical Nutrition,1997,65(6):1858-1866.
[119]赵宝路.氧自由基和天然抗氧化剂[M].北京:科学出版社,1999.3-135.
[120] TOLLE A,KOLLECK I,GUTHMANN F,et al. Vitamin E metabolism of the lung [J].Fett-Lipid,1996,98:328-331.
[121] TINGHH,TIMIMI F K,BOLES K S,et al. Vitamin C improves endothelium-dependentvasodilatation in patients with non-insulin-dependent diabetes mellitus[J]. Journal ofClinical Investigation,1996,97:22-28.
[122]邵惠训.自由基和自由基清除剂[J].生物工程进展,1994,14(4):49-50.
[123] CUI Yu,CHENG Xiao-Xin,WANG Ying,et al. Studies on the oxygen free radical inintestina tissues, hepatic tissues and sera from mice infected with Trichinella spiralis [J].Chinese Journal of Parasitic Disease Control,1998,11:35-37.
[124] MutohH,Hiraishi H,OTAS,et al. Relationships between metals ions and oxygen freeradicals in ethanol-induced damage to cultured rat gastric mucosal cells[J]. DigestiveDiseases and Sciences,1995,40:2704-2711.
[125]刘程,江小梅.当代新型食品[M].北京:北京工业大学出版社,1998.644-647.
[126]王玉萍,李翔太,尹进,等.富硒香菇食用凝胶对小鼠血清总氧自由基清除能力的影响[J].食品科学,1998,8:9-10.
[127]杨海龙,林燕文.平菇多糖的分离纯化及其对超氧自由基的效应[J].食品科学,1999,10:16-18.
[128] BOBEK P,OZDIN L,KUNIAK L. Hypocholesterolaemic and antilipoperoxidative effectof dietary oyster mushrooms (Pleurotus ostreatus) and its ethanol extract inhypercholesterolaemic rat [J]. Ceskaa Slovenska Gastroenterology.1995,49:46-49.
[129]王海宽,赵新淮,姜岩.甘草有效成分分离及其对自由基的清除能力[J].食品与机械,2000,4:45-47.
[130]欧仕益,高孔荣,黄惠华.麦麸膳食纤维抗氧化和·OH自由基清除活性的研究[J].食品工业科技,1997,5:23-27.
[131]许申鸿,杭瑚.葡萄籽化学成分分析及抗氧化性质的研究[J].食品工业科技,2000,21(2):18-20.
[132]郭长江,韦京豫,葛玉章,等.坚果类食物清除ROO·的作用[J].食品科学,2000,21(1):42-43.
[133] Swain T. Secondary compounds as protective agents [J].Am Rev Plant Physiol,1977,28:479-501.
[134]张国珍,樊瑛,丁万隆,徐丽珍.麻黄和细辛挥发油的抗真菌作用[J].植物保护学报,1995,22(4):373-374.
[135]方德秋,肖顺元.柠檬醛及香精油的抗菌性研究概述[J].天然产物研究与开发,1994,6(4):75-77.
[136]何道航.印楝素植物性杀虫剂的生物活性及应用研究[D].广州:华南农业大学,1999.
[137] Jill P. Benner, pesticidal compounds from higher plants [J].Pestic Sci,1993,39:95-102.
[138]王进忠,孙淑玲,苏红田.植物源杀虫剂的研究利用现状及展望[J].北京农学院学报,2000,15(2):72-75.
[139]刘长令.用于植物保护中天然产物[J].农药译丛,1995,17(3):15-20.
[140]侯玉霞,李重九,马立新等.中草药中抗植物病毒TMV活性物质PZ1作用机理研究[J].中国农业大学学报,2000,5(1):21-24.
[141]王利国,马祁.天然产物对植物病毒的抑制作用[J].中国生物防治,2000,16(3):127-130.
[142] Lee-Juian Lin, Galen Peiser, Bai-Ping Ying, et al. Identification of plant growth inhibitorypriciples in Ailakthusaltissima and Castela tortuosa[J]. J Agric Food Chem,1995,43:1706-1711.
[143] Yang X P, Yuan C S, Jia Z J. Two new antibacterial iridoids from Patrinia rupestris [J].ChinChem Lett,2006,17(3):337-340.
[144] Liu C H, Liu J Y, Huang L L,et al. Absolute confiquration of keisslone, a new antimicrobialmetabolite from Keissleriella sp. YS4108, a marine filamentous funqus [J].Planta Med,2003,69(5):481-483.
[145] Dai J Q, Zhao, Ch Y, et al. Two new sesquiterpenes from the Chinese herbSaussureapetroviiand their antibacterial and antitumor activity [J].J Chem Res Synopses,2001(2):74-75.
[146]吴新安,花日茂,岳永德,等.植物源抗菌、杀菌活性物质研究进展[J].安徽农业大学学报,2002,29(3):245-249.
[147]张成省,孔凡玉,刘朝科,等.枯草芽孢杆菌Tpb55抗烟草普通花叶病毒（TMV）活性研究[J].中国烟草学报,2009,15(4):48-51.
[148]高兴文,蔡学建,严凯,等.4(3H)-喹唑啉酮类Schiff碱的合成与抗烟草花叶病毒活性[J].有机化学,2008,28(10):1785-1791.
[149]谭庆伟,杜丹超,欧阳明安.天然海鱼共附生放线茵抑茵和抗病毒活性筛选研究[J].激光生物学报,2010,19(6):824-831.
[150]陈启建,董雷,欧阳明安,等.绿色荧光蛋白标记检测鸦胆子素D抗TMV活性[J].激光生物学报，2010,19(6):742-747.
[151]许玉娟,范素素,齐文静,等.苍耳多糖对烟草花叶病毒的抑制作用及对烟草几种防御酶活性的影响[J].山东农业大学学报(自然科学版),2010,41(4):485-488.
[152]Mitsuko Kishi-Kaboshi, Takashi Murata, Mitsuyasu Hasebe, et al. An extraction method fortobacco mosaic virus movement protein localizing in plasmodesmata [J]. Protoplasma (2005)225:85-92.
[153]韩凤英.抗烟草花叶病毒海洋细菌的分离鉴定及发酵产物的活性[D].福建:福建农林大学,2006,1-57.
[154]陈启建,刘莉莉,欧阳明安,等.鸦胆子素D抗黄瓜绿斑驳花叶病毒的活性[J].福建农林大学学报,2010,39(6):566-570.
[155]金光辉,尹启生,杨军,等.植物源抗烟草花叶病毒活性物质的初步筛选[J].烟草技术,2010,6:73-81.
[156]章新军,杨峰钢,高致明,等.植物源农药防治烟草病虫害[J].烟草科技，2000,6：58-60.
[2]王本祥.现代中药药理与临床[M].天津：天津科技翻译出版社,2004:740.
[3]严永清.中药辞海[M].第2卷.北京:中国医药科技出版社,1996:282-285.
[4]宋丽明摘译，江纪武校.牡丹皮中2种单萜的立体结构及自由基清除作用[J].国外医学中医中药分册，2002，24(l):29-30.
[5] Yoshikawa M, Ohata T, Kawaguchi A, et al. Bioactive constituents of Chinese naturalmedicines. V. Radical scavenging effect of Moutan Cortex.(l): Absolute stereostructures oftwo monoterpenes，paeonisuffrone and paeonisuffral [J]. Chem Pharm Bull(Tokyo)，2000，48(9):1327-1331.
[6]李方军.牡丹皮化学成分及药理作用研究进展[J].安徽医药，2004，8(1):9-10.
[7]宋丽明摘译,江纪武校.牡丹皮中牡丹苷A～E和没食子酰羟基芍药苷的结构及自由基清除作用[J].国外医学中医中药分册，2002,24(l):30-31.
[8] Yashikawa M, Uchida E，Kawaguchi A, et al. Galloyl-oxypaeoniflorin,suffruticosides A,B,C,and D, five new antioxidative glycosides and suffruticoside E, A paeonol glycoside，fromChinese Moutan Cortex[J].Chem Pharm Bull(Tokyo),1992,40(8):2248-2250.
[9] Matsuda H, Ohata T, Kawaguchi A, et al. Bioactive constituents of Chinese natural medicines.VI. Moutan Cortex.(2): structures and radical scavenging effects of suffruticosides A, B, C, D,and E and galloyl-oxypaeoniflorin.[J].Chem Pharm Bull,200l,49(l):69-72.
[10]陈悦娇,陈杰林,马应丹.丹皮挥发油化学成分的GC-MS分析[J].广州食品工业科技,2002,18(4):36-37.
[11]吴少华,马云保,罗晓东,等.丹皮的化学成分研究[J].中草药，2002，33(8):679-680.
[12] Lin HC, Ding HY, Wu YC. Two novel compounds from Paeonia suffruticosa [J].J Nat Prod,1998,61(3):343-346.
[13]刘春生,王海等.药用动植物种养加工技术·牡丹皮[M].北京:中国中医药出版社,2001:57-61.
[14]成都中医学院.中药鉴定学[M].上海:上海科技出版社,1980:239-241.
[15]张艳,范俊安.中药材牡丹皮研究概况III丹皮化学成分研究概况[J].重庆中草药研究,2008,12(2):24-29.
[16]房杏春，安登魁，董善事，等。HPLC法测定丹皮中丹皮酚含量[J].中国药科大学学报,1989,20(2):109-111.
[17]刘放,黄卫平.HPLC法测定牡丹皮及其制剂中丹皮酚含量[J].基层中药杂志,1997,11(1):34-36.
[18]章灵华,肖培根,黄艺,等.丹皮酚的药理与临床研究进展[J].中国中西医结合杂志,1996,16(3):187-189.
[19]袁金伟,屈凌波,白云亮,等。丹皮酚结构改造研究进展[J].河南工业大学学报,2011,32(2):88-93.
[20]龚明贵,张巧明,秦翠丽等.牡丹中丹皮酚含量及其提取检测方法研究[J].时珍国医国药,2007,18(3):709-711.
[21]张云升,成晓迅,和健等.牡丹皮中丹皮酚的提取工艺研究[J].河北省科学院学报,2005,22(3):49-51.
[22]方岩雄,黄剑明,张昆.用超临界CO2从丹皮中提取丹皮酚[J].精细化工，2001,18(4):201-205.
[23]王立红,周丽莉,雷雪等.超临界CO2萃取徐长卿中丹皮酚的工艺[J].沈阳药科学报,2006,23(1):53-56.
[24]李玉贤,万炎,陈晓岚等.牡丹皮中丹皮酚的提取方法研究[J].河南中医学院学报，2007,22(2):37-38.
[25]卞凌.徐长卿中丹皮酚水蒸气蒸馏法提取工艺研究[J].海峡学,2005,17(6):35-36).
[26]彭玲,李成网,张洁.蒸馏法提取丹皮中丹皮酚的工艺研究[J].安徽医药,2012,16(4):446-447.
[27]陈巧谋,陈平,王炜,等.复方延胡索片中丹皮酚β-环糊精包合物的制备研究[J].湖南中医药导报,2003,9(8):53.
[28]刘庆发,韩玉玲.正交设计法探讨牡丹皮中丹皮酚的提取工艺[J].黑龙江医药,2002,15(5):351-352.
[29]李利红,张晓静.正交试验法优选丹皮酚提取工艺[J].安徽农业科学,2008,36(14):5707
[30] Li H, Chen B, Nie L et al. Solvent Effects on Focused Microwave Assisted Extraction ofPolyphenolic Acids from Eucommia Ulmodies [J].Phytochem.Anal.,2004,15(5):306-312.
[31]宫静静,王娟,沈平孃.微波辅助萃取技术在不同药用部位的工艺研究[J].中国中药杂志,2007,32(16):1641-1643.
[32] Ye Q, Deng C H. Determination of Camphor and Borneol in Traditional Chinese Medicinesby Microwave-Assisted Extraction and Gas Chromatography with Flame IonizationDetector[J].Analytical Letters,2008,41(13):2387-2401.
[33]叶青,郑大贵.微波辅助萃取水蒸气蒸馏技术在中药有效成分分析中的应用研究[J].光谱实验室,2010,27(3):1077-1079.
[34]陈江斌，唐其柱，黄从新等.丹皮酚对心肌细胞自律性和延迟后除极的影响[J]．中国应用生理学杂志，1999，15(4)：332-334．
[35]孙言才,沈玉先，孙国平.丹皮酚的主要药理活性研究进展[J].中成药，2004，26（7）：579-582.
[36] Li L J，Zhong Z H,Chen Q．Fetal Determination of paeonol by a flow injection chemi luminessence method[J]．Chem Res Appl，2006，18(7)：886-888．
[37]严永庆，余传隆，黄泰康等主编．中药辞海(第二卷)[M]．第1版．北京：中国医药科技出版社，1996，282-287．
[38]李薇，王运亮，蔡绍皙等．丹皮酚和阿司匹林对大鼠血液流变性影响的比较[J]．中草药，2000，31(1)：29-31．
[39]胡大一.贯彻循证医学的原则，重视动脉粥样硬化的预防[J].中华心血管病杂志，2002;9(30):513-514.
[40] Ross R.The pathogenesis of atherosclerosis: a perspective for the1990s[J].Nature，1993，362:801-809.
[41]石琳，范盘生，方几希.丹皮酚对兔实验性动脉粥样硬化及血小板的抑制作用[J].中国药理学报，1988,9(6):555-558.
[42]戴敏，警晓梅，彭代银，等.丹皮酚抗鹤鹑试验性动脉粥样硬化作用[J].中国中药杂志，1999,24(8):488-490，512.
[43]戴敏，刘青云，顾承刚，等.丹皮酚对脂质过氧化反应及低密度脂蛋白氧化修饰的抑制作用[J].中国中医杂志，2000,25(10):625-627.
[44]范盘生.丹皮酚抑制培养主动脉平滑肌细胞的增殖及抗自由基作用[J].中药药理与临床,1991,7(3):13-16.
[45]苗耀诚.抗动脉粥样硬化药物研究进展[J].国外医学药学分册，1995;22(5):257
[46]陈宇，王志武，范洪学.动脉粥样硬化发生相关因素研究现状和展望[J].国外医学.老年医学分册，1999;20(4):145.
[47] Esper RJ, Vilarino JO,Maehado RA,et al. Endothelial dysfunction in normal and abnormalglucose metabolism[J]. Adv Cardiol,2008,45:17-43.
[48]刘瑾.丹皮酚干预兔实验性动脉粥样硬化的实验研究[D].山东医科大学硕士学位论文.2006.
[49]李逢春,周晓玲,磨红玲等．丹皮酚注射增强免疫功能的实验研究[J]．中国中西医结合杂志，1994，14(1)：37—38．
[50]朱作金,蔡福盛,杨志平等．丹皮酚雾化吸人对大鼠免疫功能的影响[J]．广西医科大学学报，1994，11(4)：386—387．
[51]侯福生，鲍学平.葫芦素B及牡丹酚对苯并(a)花在大鼠肝微粒体代谢的影响[J].中草药,1985,16(3):25-26.
[52] Chang HL，Hung CF，Yeh CC, et al. Paeonol promoted2-aminofluorene and p-aminobenzoicacid acetylations by mononuclear leucocytes from Sprague-Dawley rats. Cytobios，2000,103(404):149-158.
[53] Chung JG. Paeonol Promotion of DNA adducts formation and arylamines N-acetyltransferaseactivity in human colon tumor cells. Food-Chem-Toxicol.1999,37(4):327-334.
[54]孙慧君，王晓琦，于丽敏，等.丹皮酚对MDR逆转作用的研究.解剖科学进展，2000，6(1):59-61.
[55]孙国平,沈玉先,张玲玲，等.丹皮酚的体内外抗肿瘤作用.安徽医科大学学报,2002,37(3):183-185.
[56]孙国平，王华．丹皮酚诱导K-（562)细胞凋亡的研究[J]．中国药理学通报,2004,20(5)：550～552．
[57]孙国平，沈玉先，张玲玲，等.丹皮酚对HepA荷瘤小鼠免疫调节和抑瘤作用研究.中国药理学通报,2003,19(2):160-162.
[58]胡映辉,林志彬,何云庆等.灵芝菌丝体多糖通过增强小鼠巨噬细胞功能诱导HL-60细胞凋亡[J].中国药理学通报,1999,15(1):27-30.
[59] Nishmura T, Ohta S,Sato N et al. Combination tumor immunotherapy with recombinationtumor necrosis factor and recombinant interleukin2in mice. Int J Cancer,1987,40(2):255-261.
[60]葛焕琦,李乐复,王丽英,等.白细胞介素II增强肿瘤坏死因子对人肝癌细胞的细胞毒性作用.白求恩医科大学学报,1997,23(5):779-781.
[61] Vasiliki P，Prokopios Mloanna C，et a1．Volatiles with antimicmbial activity from the rootsof Greek Paeonia taxa[J]．J Ethno pharmacol，2002，8l(1)：101．
[62]杜凡,李惠芬,王宇歆,等.牡丹皮中丹皮酚、总苷、多糖单用及合用后的协同抑菌作用考查[J].天津药学,2008,20(2):10-12.
[63]文洪林,桂红,贺红.丹皮、白芍对牙龈卟啉单胞菌、具核梭杆菌的体外抑菌活性研究[J].临床和实验医学杂志.2012,11(18):1469.
[64]吴晓慧,吴国荣,张卫明,等.丹皮酚提取、磺化及对植物病原菌的抑菌试验[J].中药材,2003,26(11):778-780.
[65]李骅,王四旺,张邦乐.丹皮酚的药理活性和药物动力学研究进展[J].亚太传统医药.2010,6(2):110-112.
[66]唐景荣,石琳.丹皮酚对体外培养乳鼠心肌细胞45Ca摄取的影响[J].中国药理学与毒理学杂志,1991,5(2):108-109.
[67]唐景荣,石琳.丹皮酚对钙反常培养心肌细胞的保护作用[J].中国中药杂志,1991,16(9):557-560.
[68]唐景荣,石琳.丹皮酚磺酸钠对钙反常培养乳鼠心肌细胞Ca2+内流的抑制作用[J].药学学报,1991,26(3):161-165.
[69]刘国坤,谢联辉,林奇英,等.15种植物的单宁提取物对烟草花叶病毒(TMV)的抑制作用[J].植物病理学报.2003,33(3):279-283.
[70] Kovendi A, Beu D L, Gagiu F, et al. Resacetophenone [J]. Rom,1973,53:277.
[71] Mam R, Venkataraman K. The preparation of phenolic ketones and chalcones by means ofboron trifluoride [J]. Current Sci (India),1954,23:220-221.
[72]唐海燕、杨石、王见宾,等.丹皮酚制备工艺、剂型改革及临床应用概述.江苏中医药.2004,4:58-60.
[73]程杰,方志杰,姜宇华,等.丹皮酚的新法制备及其糖苷化衍生物的合成[J].化学研究与应用,2009,21(10),1469-1472.
[74] Windscheif P.M., Vogtle E.F. Sustituted dipyridyenes a dethynes all key pyridine buildingblokes [J].Synthesis,1994,(1):87-92.
[75]孟庆华,冀亚飞,张雁秋.丹皮酚的提取及其衍生物的合成.徐州师范大学学报.1998,16(2):41-43.
[76]潘显道,费勤志,朱承根,等.5个丹皮酚酯的合成和体外抗肿瘤活性研究.安徽医药.2004,8(1):16-18.
[77] Li W., Koike K., Asada Y. et al. Biotransformation of Paeonol by Panax ginseng root andcell cultures [J]. Journal of Molecular Catalysis Enzymatic,2005,35:117-121.
[78]程杰,方志杰,姜宇华,等.丹皮酚的新法制备及其糖苷化衍生物的合成[J].化学研究与应用,2009,21(10):1469-1472.
[79]汪显阳.正交设计法优化Peonoxyacetic Acid的合成[J].数理医药学志,2000,13(4):344-345.
[80]胡桂.丹皮酚磺酸钠制备的研究[J1.中国医院药学杂志,2004,24(5):319.
[81]李如法.以丹皮酚为母体合成的丙醇胺类醚化合物及其衍生物[P].中国专利:CN03135253.7,2004-07-21.
[82]李如法.以丹皮酚为母体合成的丙醇胺类醚化合物及其衍生物[P].中国专利:CN03135254.5,2004-07-21.
[83]祁俊生,曹阳,王远亮.丹皮酚的选择性溴化反应[J].应用化学,2003,20(7):702-703.
[84] Dey DK, Dey SP, Elmali A, et al. Crystal structure and conformation of2-{(2’-aminobenzyl)iminoethyl}-5-methoxyphenol [J]. Chemical Sciences,2001,56(4/5):375-380.
[85]朱海生.丹皮酚Schiff碱与氨基磷酸酯衍生物的合成研究[D].2011,郑州大学硕士学位论文.
[86]王学军,刘建利,王江凯.丹皮酚衍生物的合成及其抗肿瘤细胞增殖研究[J].药学学报,2012,47(1):72-76.
[87]姚日生,李发,邓胜松,等.丹皮酚单硝化与二硝化衍生物的合成[J].合肥工业大学学报,2009,32(2):177-180.
[88]曹阳,罗琦,祁俊生,等.2-羟基-4-甲氧基-5-胂酸基苯乙酮的合成[J].重庆三峡学院学报,2003,19(2):125-126.
[89] Patel VK, Vasanwala AM, Jejurkar CR. Synthesis of mixed Schiff base complexes of copper(II) and nickel (II) and their spectral, magnetic and antifungal studies [J]. India J Chem SectA,1989,28a (8):719-721.
[90] XU T-T, XU X-Y, GAO J, et al. Synthesis, Structure and Antimicrobial study ofN-Salicylidene-Phenylpropanolamine Bicopper (II) Complex [J]. Synthesis and Reactivity inInorganic, Metal-Organic and Nano-Metal Chemistry,2006,36:667-672.
[91] XU T-T, XU X-Y, GAO J, et al. Crystal and Molecular Structure of two new Schiff bases:paeonol-ethylenediamine and paeonol-1,3-propylenediamine [J]. Journal of StructureChemistry (Russia),2007,48(1):C161-165.
[92]石鑫.丹皮酚三氮唑衍生物的合成及工艺研究[D].河南师范大学硕士学位论文,2012.
[93]王铮，任天池，乔淑珍.丹皮酚-β-环糊精包合物的研究[J].中国药学杂志,1989,24(7):4102-4104.
[94]王江恺.丹皮酚及其衍生物的合成与抗肿瘤活性研究[D].西北大学硕士论文,2010.
[95]曹阳.丹皮酚胂化合物诱导肝癌细胞HepG2凋亡及分子机制探讨[D].重庆大学硕士学位论文,2004.
[96]杜君.丹皮酚磺酸钠注射液穴位注射治疗颈椎病60例临床观察[J].医学信息,2007,20(10):1855-1856.
[97]朱越.丹皮酚磺酸钠注射液治疗中枢性高热临床观察.实用医技杂志,2008,15(3):333-334.
[98]胡丽娟.丹皮酚磺酸钠注射液与利多卡因合用减轻肌内疼痛的临床观察.医学信息,2007,20(11):1999-2000.
[99]谌曦,黄传兵,张皖东,等.四妙散加减合丹皮酚磺酸钠治疗急性痛风性关节炎临床研究[J].中国中医药信息杂志,2011,18(4):66-67.
[100]李永忻.丹皮酚磺酸钠注射液促进骨折愈合的疗效观察.实用药物与临床.2007,10(4):220-221.
[101]吴晓慧,吴国荣,张卫明,等.丹皮酚及其磺化物体外抗氧化作用[J].南京师大学报(自然科学版),2005,28(3):83-85.
[102]沈奇,金春雁,缪月秋,等.丹皮酚磺酸钠对樱桃番茄的保鲜作用的研究[J].食品科学,2005,26(4):256-259.
[103]吴婷,沈奇,吴晓慧,等.丹皮酚及其磺化物对樱桃番茄果实的保鲜作用比较研究[J].食品科学,2007,28(2),330-334.
[104]常福辰,吴国荣,吴晓慧,等.丹皮酚磺酸钠对蒌蒿的保鲜作用.南京师大学报(自然科学版),2005,28(2):88-91.
[105] XU T-T, XU X-Y, GAO J, et al. Synthesis, Structure and Antimicrobial study ofN-Salicylidene-Phenylpropanolamine Bicopper (II) Complex [J]. Synthesis and Reactivityin Inorganic, Metal-Organic and Nano-Metal Chemistry,2006,36:667-672.
[106]许同桃.丹皮酚金属配合物的合成及生物活性研究.时珍国医国药.2009,20(4):917-919.
[107]高健,相海鹰,许同桃,等。丹皮酚及其席夫碱衍生物的抑菌性研究.化学试剂,2007,29(1):59-60.
[108]于曙光,郑国生,潘大仁.丹皮酚合成过程中抑菌活性的变化研究.化学与生物工程,2012,29(8):56-58.
[109] FRENETTE R, GAUTHIER J Y, YOUNG R N, et al. Stereo selective synthesis ofleukotriene antagonists: US,4857659[P].1989-08-15.
[110]林宝玉.浅谈自由基对人体的危害及清除方法.中国西部科技[J].2007(18).
[111]熊双丽，李安林，金征宇.猪喉软骨硫酸软骨素体外超氧阴离子自由基清除机理探讨［J］.食品科学.2008，29(2):362-365.
[112]杨保收，陈越，金久善等.氧自由基检测方法在生物学和医学中的应用［J］.动物科学与动物医学.1999，7，(16):17-18.
[113]范秀萍，吴红棉，王娅楠等.4种贝类糖胺聚糖体外清除自由基活性的比较［J］.食品科技.2008，2(33):165-167.
[114］彭长连，陈少薇，林植芳，等.用有机自由基DPPH·法评价植物抗氧化能力［J］.生物化学与生物物理进展，2000，27(6):658-661.
[115]郑晶泉.抗氧化剂抗氧化实验研究进展.国外医学卫生学分册[J].2000，27(l):55-56.
[116]徐清萍,敖宗华,陶文沂.恒顺香醋DPPH·自由基清除活性成分的研究[J].中国调味品,2004(7):19-23.
[117]郑建仙.功能性食品[M].北京:中国轻工出版社,1995.344-378.
[118] WINKLHOFER Roob BM,ELLEMUNTERH,FRUHWIRTHM,et al. Plasma vitamin Cconcentrations in patients with cystic fibrosis: evidence of associations with lunginflammation [J]. American Journal of Clinical Nutrition,1997,65(6):1858-1866.
[119]赵宝路.氧自由基和天然抗氧化剂[M].北京:科学出版社,1999.3-135.
[120] TOLLE A,KOLLECK I,GUTHMANN F,et al. Vitamin E metabolism of the lung [J].Fett-Lipid,1996,98:328-331.
[121] TINGHH,TIMIMI F K,BOLES K S,et al. Vitamin C improves endothelium-dependentvasodilatation in patients with non-insulin-dependent diabetes mellitus[J]. Journal ofClinical Investigation,1996,97:22-28.
[122]邵惠训.自由基和自由基清除剂[J].生物工程进展,1994,14(4):49-50.
[123] CUI Yu,CHENG Xiao-Xin,WANG Ying,et al. Studies on the oxygen free radical inintestina tissues, hepatic tissues and sera from mice infected with Trichinella spiralis [J].Chinese Journal of Parasitic Disease Control,1998,11:35-37.
[124] MutohH,Hiraishi H,OTAS,et al. Relationships between metals ions and oxygen freeradicals in ethanol-induced damage to cultured rat gastric mucosal cells[J]. DigestiveDiseases and Sciences,1995,40:2704-2711.
[125]刘程,江小梅.当代新型食品[M].北京:北京工业大学出版社,1998.644-647.
[126]王玉萍,李翔太,尹进,等.富硒香菇食用凝胶对小鼠血清总氧自由基清除能力的影响[J].食品科学,1998,8:9-10.
[127]杨海龙,林燕文.平菇多糖的分离纯化及其对超氧自由基的效应[J].食品科学,1999,10:16-18.
[128] BOBEK P,OZDIN L,KUNIAK L. Hypocholesterolaemic and antilipoperoxidative effectof dietary oyster mushrooms (Pleurotus ostreatus) and its ethanol extract inhypercholesterolaemic rat [J]. Ceskaa Slovenska Gastroenterology.1995,49:46-49.
[129]王海宽,赵新淮,姜岩.甘草有效成分分离及其对自由基的清除能力[J].食品与机械,2000,4:45-47.
[130]欧仕益,高孔荣,黄惠华.麦麸膳食纤维抗氧化和·OH自由基清除活性的研究[J].食品工业科技,1997,5:23-27.
[131]许申鸿,杭瑚.葡萄籽化学成分分析及抗氧化性质的研究[J].食品工业科技,2000,21(2):18-20.
[132]郭长江,韦京豫,葛玉章,等.坚果类食物清除ROO·的作用[J].食品科学,2000,21(1):42-43.
[133] Swain T. Secondary compounds as protective agents [J].Am Rev Plant Physiol,1977,28:479-501.
[134]张国珍,樊瑛,丁万隆,徐丽珍.麻黄和细辛挥发油的抗真菌作用[J].植物保护学报,1995,22(4):373-374.
[135]方德秋,肖顺元.柠檬醛及香精油的抗菌性研究概述[J].天然产物研究与开发,1994,6(4):75-77.
[136]何道航.印楝素植物性杀虫剂的生物活性及应用研究[D].广州:华南农业大学,1999.
[137] Jill P. Benner, pesticidal compounds from higher plants [J].Pestic Sci,1993,39:95-102.
[138]王进忠,孙淑玲,苏红田.植物源杀虫剂的研究利用现状及展望[J].北京农学院学报,2000,15(2):72-75.
[139]刘长令.用于植物保护中天然产物[J].农药译丛,1995,17(3):15-20.
[140]侯玉霞,李重九,马立新等.中草药中抗植物病毒TMV活性物质PZ1作用机理研究[J].中国农业大学学报,2000,5(1):21-24.
[141]王利国,马祁.天然产物对植物病毒的抑制作用[J].中国生物防治,2000,16(3):127-130.
[142] Lee-Juian Lin, Galen Peiser, Bai-Ping Ying, et al. Identification of plant growth inhibitorypriciples in Ailakthusaltissima and Castela tortuosa[J]. J Agric Food Chem,1995,43:1706-1711.
[143] Yang X P, Yuan C S, Jia Z J. Two new antibacterial iridoids from Patrinia rupestris [J].ChinChem Lett,2006,17(3):337-340.
[144] Liu C H, Liu J Y, Huang L L,et al. Absolute confiquration of keisslone, a new antimicrobialmetabolite from Keissleriella sp. YS4108, a marine filamentous funqus [J].Planta Med,2003,69(5):481-483.
[145] Dai J Q, Zhao, Ch Y, et al. Two new sesquiterpenes from the Chinese herbSaussureapetroviiand their antibacterial and antitumor activity [J].J Chem Res Synopses,2001(2):74-75.
[146]吴新安,花日茂,岳永德,等.植物源抗菌、杀菌活性物质研究进展[J].安徽农业大学学报,2002,29(3):245-249.
[147]张成省,孔凡玉,刘朝科,等.枯草芽孢杆菌Tpb55抗烟草普通花叶病毒（TMV）活性研究[J].中国烟草学报,2009,15(4):48-51.
[148]高兴文,蔡学建,严凯,等.4(3H)-喹唑啉酮类Schiff碱的合成与抗烟草花叶病毒活性[J].有机化学,2008,28(10):1785-1791.
[149]谭庆伟,杜丹超,欧阳明安.天然海鱼共附生放线茵抑茵和抗病毒活性筛选研究[J].激光生物学报,2010,19(6):824-831.
[150]陈启建,董雷,欧阳明安,等.绿色荧光蛋白标记检测鸦胆子素D抗TMV活性[J].激光生物学报，2010,19(6):742-747.
[151]许玉娟,范素素,齐文静,等.苍耳多糖对烟草花叶病毒的抑制作用及对烟草几种防御酶活性的影响[J].山东农业大学学报(自然科学版),2010,41(4):485-488.
[152]Mitsuko Kishi-Kaboshi, Takashi Murata, Mitsuyasu Hasebe, et al. An extraction method fortobacco mosaic virus movement protein localizing in plasmodesmata [J]. Protoplasma (2005)225:85-92.
[153]韩凤英.抗烟草花叶病毒海洋细菌的分离鉴定及发酵产物的活性[D].福建:福建农林大学,2006,1-57.
[154]陈启建,刘莉莉,欧阳明安,等.鸦胆子素D抗黄瓜绿斑驳花叶病毒的活性[J].福建农林大学学报,2010,39(6):566-570.
[155]金光辉,尹启生,杨军,等.植物源抗烟草花叶病毒活性物质的初步筛选[J].烟草技术,2010,6:73-81.
[156]章新军,杨峰钢,高致明,等.植物源农药防治烟草病虫害[J].烟草科技，2000,6：58-60.