牛樟芝固态发酵产物的降胆固醇作用
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摘要
本实验主要探究牛樟芝(S-29)固态发酵产物对高脂饮食小鼠胆固醇调节的影响。小鼠随机分为正常组、高脂模型组、护肝片阳性对照组、固态发酵组及液态发酵组;小鼠经高脂饲料喂养6周,相应物质灌胃4周。检测小鼠血清及肝脏相关指标; q-PCR检测胆固醇代谢相关基因的mRNA表达量。结果表明,与模型组比较,固态发酵组小鼠血清游离脂肪酸(NEFA)及谷丙转氨酶(ALT)浓度显著降低,分别降低了38. 5%和40. 7%;肝脏总胆固醇(TC)浓度显著降低,降低了23. 5%;低密度脂蛋白受体(LDL-R)的mRNA表达量显著增加,增加了3. 6倍。结果证明,牛樟芝固态发酵产物具有较好的降胆固醇作用,其主要机制可能是通过上调LDL-R基因的表达,以促进胆固醇的分解代谢,进而降低小鼠体内胆固醇浓度。
The cholesterol regulation efficacy of Antrodia camphorata( S-29) produced by solid state fermentation( SSF)in mice with high fat diet was studied. The mice were randomly divided into normal group,high fat model group,liverprotecting tablet positive control group,solid-state fermentation group and submerged fermentation group. The mice were fed with high fat diet for 6 weeks,and the corresponding substances were given for 4 weeks. The serum and liver relevant indexes of the mice were measured,and the mRNA expression levels of genes related to cholesterol metabolism were analyzed by q-PCR. Comparing to those in the model group,the NEFA and ALT concentrations of serum in the solid-state fermentation group were significantly decreased by 38. 5% and 40. 7%,respectively; the liver TC concentration was significantly decreased by 23. 5%; and the mRNA expression level of LDL-R was significantly increased by 3. 6 times.The above results suggested that the solid fermentation products of Antrodia camphorata had good cholesterol-lowering effects,and its main mechanism might be to up-regulate the expression of LDL-R gene in order to promote cholesterol catabolism and then reduce cholesterol concentration in mice.
The cholesterol regulation efficacy of Antrodia camphorata( S-29) produced by solid state fermentation( SSF)in mice with high fat diet was studied. The mice were randomly divided into normal group,high fat model group,liverprotecting tablet positive control group,solid-state fermentation group and submerged fermentation group. The mice were fed with high fat diet for 6 weeks,and the corresponding substances were given for 4 weeks. The serum and liver relevant indexes of the mice were measured,and the mRNA expression levels of genes related to cholesterol metabolism were analyzed by q-PCR. Comparing to those in the model group,the NEFA and ALT concentrations of serum in the solid-state fermentation group were significantly decreased by 38. 5% and 40. 7%,respectively; the liver TC concentration was significantly decreased by 23. 5%; and the mRNA expression level of LDL-R was significantly increased by 3. 6 times.The above results suggested that the solid fermentation products of Antrodia camphorata had good cholesterol-lowering effects,and its main mechanism might be to up-regulate the expression of LDL-R gene in order to promote cholesterol catabolism and then reduce cholesterol concentration in mice.
引文
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[23]CHIANG J Y.Regulation of bile acid synthesis:pathways,nuclear receptors,and mechanisms[J].J Hepatol,2004,40(3):539-551.
[24]SHARPE L J,BROWN A J.Controlling cholesterol synthesis beyond 3-hydroxy-3-methylglutaryl-CoA reductase(HMGCR)[J].J Biol Chem,2013,288(26):18707-18715.
[25]HAN KH,IIJUKA M,SHIMADAhimada K,et al.Adzuki resistant starch lowered serum cholesterol and hepatic 3-hydroxy-3-methylglutaryl-CoA mRNA levels and increased hepatic LDL-receptor and cholesterol 7α-hydroxylase mRNA levels in rats fed a cholesterol diet[J].Br J Nutr,2005,94(6):902-908.
[26]YAN L P,CHAN S W,CHAN A S,et al.Puerarin decreases serum total cholesterol and enhances thoracic aorta endothelial nitric oxide synthase expression in diet-induced hypercholesterolemic rats[J].Life Sci,2006,79(4):324-330.
[2]KEYS A.Coronary heart disease,serum cholesterol,and the diet[J].Acta Med Scand,1980,207(3):153-160.
[3]BJ?RKBACKA H,KUNJATHOOR V V,MOORE K J,et al.Reduced atherosclerosis in My D88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways[J].Nat Med,2004,10(4):416-421.
[4]WU S H,RYVAREDN L,CHANG T T.Antrodia camphorata(“niu-chang-chih”),new combination on medicinal fungus in Taiwan[J].Bot Bull Acad Sinica,1997,38(4):273-275.
[5]HSIAO G,SHEN M Y,LIN K H,et al.Antioxidative and hepatoprotective effects of Antrodia camphorata extract[J].J Agric Food Chem,2003,51(11):3302-3308.
[6]HSEU Y C,WU F Y,WU J J,et al.Anti-inflammatory potential of Antrodia Camphorata through inhibition of i NOS,COX-2and cytokines via the NF-kappaB pathway[J].Int Immunopharmacol,2005,5(13-14):1914-1925.
[7]AO Z H,XU Z H,LU Z M,et al.Niuchangchih(Antrodia camphorata)and its potential in treating liver diseases[J].JEthnopharmacol,2009,121(2):194-212.
[8]YEN I C,YAO C W,KUO M T,et al.Anti-cancer agents derived from solid-state fermented Antrodia camphorata mycelium[J].Fitoterapia,2015,102:115-119.
[9]LAI M N,KO H J,NG L T.Hypolipidemic effects of Antrodia cinnamomea extracts in high-fat diet-fed hamsters[J].J Food Biochem,2012,36(2):233-239.
[10]KUO Y H,LIM C H,SHIH C C,et al.Antcin K,a triterpenoid compound from Antrodia camphorata,displays antidiabetic and antihyperlipidemic effects via glucose Transporter 4 and AMP-activated protein kinase phosphorylation in muscles[J].Evid Based Complement Alternat Med,2016:4867092.
[11]KUO Y H,LIN C H,SHIH C C.Antidiabetic and antihyperlipidemic properties of a triterpenoid compound,dehydroeburicoic acid,from Antrodia camphorata in Vitro and in streptozotocin-induced mice[J].J Agric Food Chem,2015,63(46):10140-10151.
[12]KUO Y H,LIN C H,SHIH C C.Ergostatrien-3β-ol from Antrodia camphorata inhibits diabetes and hyperlipidemia in high-fatdiet treated mice via regulation of hepatic related genes,glucose transporter 4,and AMP-activated protein kinase phosphorylation[J].J Agric Food Chem,2015,63(9):2479-2489.
[13]刘晓凤,MmanywaMarim Said,赵庆,等.樟芝固态发酵产物抗氧化性分析[J].工业微生物,2016,46(6):34-40.
[14]夏永军.樟芝菌发酵生产Antrodins等活性产物的研究[D].无锡:江南大学,2012.
[15]周璇,夏永军,刘胜男,等.不同培养方式对牛樟芝活性组分的影响[J].工业微生物,2017,47(2):18-23.
[16]寇淑鸣.黄连生物碱对HepG2细胞和金黄地鼠的协同降胆固醇活性及机制研究[D].重庆:西南大学,2016.
[17]SHI Y,GUO R,WANG X,et al.The regulation of alfalfa saponin extract on key genes involved in hepatic cholesterol metabolism in hyperlipidemic rats[J].PLo S One,2014,9(2):e88282.
[18]MATSUYAMA H,SATOato K,NAKAMURA Y,et al.Modulation of regulatory factors involved in cholesterol metabolism in response to feeding of pravastatin-or cholesterol-supplemented diet in chickens[J].Biochim Biophys Acta,2005,1734(2):136-142.
[19]VIGAN? T,HERNANDEZ A,CORSINI A,et al.Mevalonate pathway and isoprenoids regulate human bronchial myocyte proliferation[J].Eur J Pharmacol,1995,291(2):201-203.
[20]MEDINA M W,KRAUSS R M.The role of HMGCR alternative splicing in statin efficacy[J].Trends Cardiovasc Med,2009,19(5):173-177.
[21]GOLDSTEIN J L,BROWN M S.Regulation of the mevalonate pathway[J].Nature,1990,343(6257):425-430.
[22]SOUTAR A K.Intracellular transport of the low-density lipoprotein receptor[J].Biochem Soc Trans,1996,24(2):547-552.
[23]CHIANG J Y.Regulation of bile acid synthesis:pathways,nuclear receptors,and mechanisms[J].J Hepatol,2004,40(3):539-551.
[24]SHARPE L J,BROWN A J.Controlling cholesterol synthesis beyond 3-hydroxy-3-methylglutaryl-CoA reductase(HMGCR)[J].J Biol Chem,2013,288(26):18707-18715.
[25]HAN KH,IIJUKA M,SHIMADAhimada K,et al.Adzuki resistant starch lowered serum cholesterol and hepatic 3-hydroxy-3-methylglutaryl-CoA mRNA levels and increased hepatic LDL-receptor and cholesterol 7α-hydroxylase mRNA levels in rats fed a cholesterol diet[J].Br J Nutr,2005,94(6):902-908.
[26]YAN L P,CHAN S W,CHAN A S,et al.Puerarin decreases serum total cholesterol and enhances thoracic aorta endothelial nitric oxide synthase expression in diet-induced hypercholesterolemic rats[J].Life Sci,2006,79(4):324-330.
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