五加科植物中药对胆固醇的调节作用及机制研究进展
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摘要
五加科植物中药三七、人参、西洋参等是我国名贵中药材,具有抗炎、抗衰老等作用,对心脑血管系统有明显影响。研究发现其对胆固醇代谢和转运可能影响心脑血管系统的功能,总胆固醇(TC)可分为高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C),胆固醇具有很多生理调节作用,HDL-C对心血管有保护作用,当体内胆固醇代谢出现紊乱、LDL-C增高等则会增加心脑血管疾病的危险。通过查阅近几年相关中外文献资料,笔者发现五加科植物中药对胆固醇具有明显的调节作用,能够直接调节实验性高血脂大鼠胆固醇水平,均能降低大鼠体内TC和LDL-C,部分能升高大鼠体内HDL-C水平;可以通过抑制胆固醇合成调控基因肝X受体(LXR-α),过氧化物酶体增殖剂激活受体γ(PPARγ),细胞色素P450 7A1(CYP7A1)等从而抑制胆固醇的合成;可以通过上调胆固醇代谢基因过氧化物酶体增殖剂激活受体α(PPARα),PPARγ,CYP8B1,CYP7A1,LXR和转运体腺苷三磷酸结合转运蛋白(ABCA1,ABCG5/8)等从而促进体内胆固醇代谢;五加科植物可能通过调节脑内胆固醇代谢和转运从而发挥神经保护作用,改善神经退行性疾病,五加科植物对脑内胆固醇代谢和转运的研究将成为未来的研究热点。以上综述希望能够为五加科中药降脂作用及机制的进一步研究提供参考思路。
Araliaceae plant Notoginseng Radix et Rhizoma,Ginseng Radix et Rhizoma and Panacix Quinquefolii Radix are famous Chinese herbal medicines,with anti-inflammatory and anti-aging effect,as well as obvious effect on cardiovascular and cerebrovascular systems. Studies have found that the metabolism and transport of cholesterol may affect the function of the cardiovascular system. Cholesterol can be divided into high-density cholesterol and low-density cholesterol. Cholesterol has many physiological regulating effect. High-density cholesterol has a protective effect on cardiovascular disease. When the cholesterol metabolism in the body is disordered,low-density cholesterol is increased,and will cause the increase in the risk of cardiovascular and cerebrovascular diseases. By consulting relevant Chinese and foreign documents and materials,we found that traditional Chinese medicine Araliaceae has a significant regulatory effect on cholesterol. It can directly regulate the cholesterol level of experimental hyperlipidemia rats,reduce total cholesterol( TC) and low density lipoprotein cholesterol( LDL-C) in rats,and partially increase high-density lipoprotein cholesterol( HDL-C) level in rats. It can inhibit cholesterol synthesis by inhibiting cholesterol synthesis-regulating genes liver X receptor-α( LXR-α),peroxisome proliferator-activated receptor γ( PPARγ),cytochrome P4507A1( CYP7A1); and up-regulate cholesterol metabolism genes peroxisome proliferator-activated receptor-α( PPARα), PPARγ, CYP8B1,CYP7A1,LXR) and body ATP-binding cassette transporter,ABC transporter( ABCA1,ABCG5/8) to promote cholesterol metabolism in the body. Araliaceae plants may play a neuroprotective role by regulating cholesterol metabolism and transport in the brain,and improve neurodegenerative diseases. Studies on the effect of Araliaceae plants on the metabolism and transport of cholesterol in brain will become a hot research topic in the future. The above review is expected to provide a reference for further research on the lipid-lowering effect and mechanism of Araliaceae plants.
Araliaceae plant Notoginseng Radix et Rhizoma,Ginseng Radix et Rhizoma and Panacix Quinquefolii Radix are famous Chinese herbal medicines,with anti-inflammatory and anti-aging effect,as well as obvious effect on cardiovascular and cerebrovascular systems. Studies have found that the metabolism and transport of cholesterol may affect the function of the cardiovascular system. Cholesterol can be divided into high-density cholesterol and low-density cholesterol. Cholesterol has many physiological regulating effect. High-density cholesterol has a protective effect on cardiovascular disease. When the cholesterol metabolism in the body is disordered,low-density cholesterol is increased,and will cause the increase in the risk of cardiovascular and cerebrovascular diseases. By consulting relevant Chinese and foreign documents and materials,we found that traditional Chinese medicine Araliaceae has a significant regulatory effect on cholesterol. It can directly regulate the cholesterol level of experimental hyperlipidemia rats,reduce total cholesterol( TC) and low density lipoprotein cholesterol( LDL-C) in rats,and partially increase high-density lipoprotein cholesterol( HDL-C) level in rats. It can inhibit cholesterol synthesis by inhibiting cholesterol synthesis-regulating genes liver X receptor-α( LXR-α),peroxisome proliferator-activated receptor γ( PPARγ),cytochrome P4507A1( CYP7A1); and up-regulate cholesterol metabolism genes peroxisome proliferator-activated receptor-α( PPARα), PPARγ, CYP8B1,CYP7A1,LXR) and body ATP-binding cassette transporter,ABC transporter( ABCA1,ABCG5/8) to promote cholesterol metabolism in the body. Araliaceae plants may play a neuroprotective role by regulating cholesterol metabolism and transport in the brain,and improve neurodegenerative diseases. Studies on the effect of Araliaceae plants on the metabolism and transport of cholesterol in brain will become a hot research topic in the future. The above review is expected to provide a reference for further research on the lipid-lowering effect and mechanism of Araliaceae plants.
引文
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[2] Nebert D W, Wikvall K, Miller W L. Human cytochromes P450 in health and disease[J]. Philos Trans R Soc Lond B Biol Sci,2013,doi:10. 1098/rstb.2012. 04311.
[3] Yusuf S,Bosch J, Dagenais G, et al. Cholesterol lowering in intermediate-risk persons without cardiovascular disease[J]. N Engl J Med,2016,374(21):2021-2031.
[4] Pikuleva I A,Waterman M R. Cytochromes p450:roles in diseases[J]. J Biol Chem,2013,288(24):17091-17098.
[5] Lorbek G,Lewinska M,Rozman D. Cytochrome P450s in the synthesis of cholesterol and bile acids-from mouse models to human diseases[J]. FEBS J,2012,279(9):1516-1533.
[6] Ferrebee C B, Dawson P A. Metabolic effects of intestinal absorption and enterohepatic cycling of bile acids[J]. Acta Pharm Sin B,2015,5(2):129-134.
[7] Yamanashi Y, Takada T, Kurauchi R, et al.Transporters for the intestinal absorption of cholesterol,vitamin E,and vitamin K[J]. J Atheroscler Thromb,2017,24(4):347-359.
[8] Urano Y,Ochiai S,Noguchi N. Suppression of amyloid-βproduction by 24S-hydroxycholesterol via inhibition of intracellularamyloid precursor protein trafficking[J].FASEB J,2013,27(10):4305-4315.
[9] Djelti F,Braudeau J, Hudry E, et al. CYP46A1inhibition, brain cholesterol accumulation and neurodegeneration pave the way for Alzheimer's disease[J]. Brain,2015,138(Pt 8):2383-2398.
[10] Burlot M A,Braudeau J,Michaelsen-Preusse K,et al.Cholesterol 24-hydroxylase defect is implicated in memory impairments associated with Alzheimer-like Tau pathology[J]. Hum Mol Genet, 2015,24(21):5965-5976.
[11] Boussicault L,Alves S,Lamazière A,et al. CYP46A1,the rate-limiting enzyme for cholesterol degradation,is neuroprotective in Huntington's disease[J]. Brain,2016,139(Pt3):953-970.
[12] WANG N,Yvan-Charvet L,Lütjohann D,et al. ATPbinding cassette transporters G1 and G4 mediate cholesterol and desmosterol efflux to HDL and regulate sterol accumulation in the brain[J]. FASEB J,2008,22(4):1073-1082.
[13] Sano O,Tsujita M,Shimizu Y,et al. ABCG1 and ABCG4 suppressγ-secretase activity and amyloidβproduction[J]. PLo S One,2016,11(5):e0155400.
[14] Parikh M,Patel K,Soni S,et al. Liver X receptor:a cardinal target for atherosclerosis and beyond[J]. J Atheroscler Thromb,2014,21:519-531.
[15] Juǐica J,DovrtělováG,NoskováK,et al. Bile acids,nuclear receptors and cytochrome P450[J]. Physiol Res,2016,65(S4):S427-S440.
[16] Ikhlef S, Berrougui H, Kamtchueng S O, et al.Paraoxonase 1-treated ox LDL promotes cholesterol efflux from macrophages by stimulating the PPARγ-LXRα-ABCA1 pathway[J]. FEBS Lett,2016,590(11):1614-1629.
[17] Courtney R,Landreth G E. LXR regulation of brain cholesterol:from development to disease[J]. Trends Endocrinol Metab,2016,27(6):404-414.
[18]国家药典委员会.中华人民共和国药典.一部[M].北京:中国医药科技出版社,2015:11-12.
[19]李娟,王如锋,杨莉,等.三七皂苷类成分及对心血管作用的研究进展[J].中国中药杂志,2015,40(17):3480-3487.
[20]姚梦杰,吕金朋,张乔,等.人参化学成分及药理作用研究[J].吉林中医药,2017,37(12):1261-1263.
[21]王巍,苏光悦,胡婉琦,等.近10年人参皂苷对心血管疾病的药理作用研究进展[J].中草药,2016,47(20):3736-3741.
[22]尚金燕,李桂荣,邵明辉,等.西洋参的药理作用研究进展[J].人参研究,2016,28(6):49-51.
[23] Cicero A F, Vitale G, Savino G, et al. Panax notoginseng(Burk.)effects on fibrinogen and lipid plasma level in rats fed on a high-fat diet[J]. Phytother Res,2003,17(2):174-178.
[24] SUN Z Z,TAN X H,YE H Q,et al. Effects of dietary Panax notoginseng extract on growth performance,fish composition,immune responses,intestinal histology and immune related genes expression of hybrid grouper(Epinephelus lanceolatus×Epinephelus fuscoguttatus♀)fed high lipid diets[J]. Fish Shellfish Immunol,2018,73:234-244.
[25] XIA W,SUN C,ZHAO Y,et al. Hypolipidemic and antioxidant activities of sanchi(Radix Notoginseng)in rats fed with a high fat diet[J]. Phytomedicine,2011,18(6):516-520.
[26] LIU Y,ZHANG HG,JIA Y,et al. Panax notoginseng saponins attenuate atherogenesis accelerated by zymosan in rabbits[J]. Biol Pharm Bull,2010,33:1324-1330.
[27]李林子,吕圭源,陈素红,等.三七叶总皂苷对高脂血症大鼠血脂、肝功能及脂质过氧化的影响[J].中国现代应用药学,2014,31(6):662-666.
[28]赵文萃,张宁,周慧琴,等.三七总黄酮对高血脂大鼠血脂的影响[J].中国实验方剂学杂志,2016,22(8):143-147.
[29] WAN J Y,HUANG W H,ZHENG W,et al. Multiple effects of ginseng berry polysaccharides:plasma cholesterol level reduction and enteric neoplasm prevention[J]. Am J Chin Med,2017,45:1293-1307.
[30] CHEN G L,LI H J,ZHAO Y,et al. Saponins from stems and leaves of Panax ginseng prevent obesity via regulating thermogenesis, lipogenesis and lipolysis in high-fat diet-induced obese C57BL/6 mice[J]. Food Chem Toxicol,2017,106:393-403.
[31] Vuksan V,XU Z Z,Jovanovski E,et al. Efficacy and safety of American ginseng(Panax quinquefolius L.)extract on glycemic control and cardiovascular risk factors in individuals with type 2 diabetes:a doubleblind,randomized,cross-over clinical trial[J]. Eur J Nutr,2018,doi:10. 1007/s00394-018-1642-0.
[32] Yoo K M,Lee C,Lo Y M,et al. The hypoglycemic effects of American red ginseng(Panax quinquefolius L.)on a diabetic mouse model[J]. J Food Sci,2012,77(7):H147-152.
[33]童晔玲,杨锋,戴关海,等.蜂胶西洋参软胶囊降血脂功能的实验研究[J].中华中医药学刊,2013,31(3):569-570.
[34]王晶,张天英,胡洋,等.西洋参皂苷对大鼠实验性高血脂的影响分析[J].黑龙江医药科学,2015,38(6):125-127.
[35]戴小慧,金圣煊.西洋参皂苷对大鼠实验性高血脂的影响[J].中华中医药学刊,2009,27(6):1300-1301.
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