小檗碱调节糖脂代谢及其抗糖尿病活性的研究
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摘要
小檗碱(berberine,BBR)是中药黄连的主要活性成分,属于异喹啉类生物碱,具有广谱抗菌作用。近年来发现它还有降血糖、降血脂、免疫调节及改善充血性心力衰竭等药理作用。研究表明,BBR能够改善糖尿病相关疾病的症状,且作用广泛,不仅可影响编码基因的表达,还与miRNA和lncRNA等非编码基因关系密切,涉及糖脂代谢、肠道菌群等多个方面。该文拟就BBR调节糖脂代谢及其抗糖尿病活性的研究进展做一综述。
Berberine(BBR) is an isoquinoline alkaloid originally isolated from Chinese herb Coptis chinensis Franch(Huanglian), which has a broad-spectrum antibacterial effect as the main active ingredient of R. coptidis.Recently, it has been found that it has the pharmacological effects of lowering blood glucose, reducing blood lipid,regulating immunity and improving the symptom of congestive heart failure, etc. But the mechanisms remain to be studied. Previous researches show that BBR may improve the symptoms of type 2 diabetes(T2D) and its complications, and then exert global anti-diabetic effects by regulating a few coding genes, but also noncoding RNAs, such as miRNAs and lncRNAs. In this paper, the research progress of BBR regulating genes expression on glucolipid metabolism and its anti-diabetic activities was reviewed.
Berberine(BBR) is an isoquinoline alkaloid originally isolated from Chinese herb Coptis chinensis Franch(Huanglian), which has a broad-spectrum antibacterial effect as the main active ingredient of R. coptidis.Recently, it has been found that it has the pharmacological effects of lowering blood glucose, reducing blood lipid,regulating immunity and improving the symptom of congestive heart failure, etc. But the mechanisms remain to be studied. Previous researches show that BBR may improve the symptoms of type 2 diabetes(T2D) and its complications, and then exert global anti-diabetic effects by regulating a few coding genes, but also noncoding RNAs, such as miRNAs and lncRNAs. In this paper, the research progress of BBR regulating genes expression on glucolipid metabolism and its anti-diabetic activities was reviewed.
引文
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[3]Lan JR,Zhao YY,Dong FX,et al.Meta-analysis of the effect and safety of berberine in the treatment of type 2diabetes mellitus,hyperlipemia and hypertension.JEthnopharmacol,2015,161:69-81
[4]Ni YX.Therapeutic effect of berberine on 60 patients with typeⅡdiabetes mellitus and experimental research.Chn J Integr Med,1988,8:711-3,707
[5]Kong W,Wei J,Abidi P,et al.Berberine is a novel cholesterol lowering drug working through a unique mechanism distinct from statins.Nat Med,2004,10:1344-51
[6]Yin J,Chen MD,Tang JF,et al.Effects of berberine on glucose and lipid metabolism in animal experiment.Chin J Diabetes,2004,12:215-8
[7]孔维佳.小檗碱降低血清胆固醇的作用与分子机理研究[D].北京:中国协和医科大学,2004
[8]Seidah NG,Awan Z,Chretien M.PCSK9:a key modulator of cardiovascular health.Circ Res,2014,114:1022-36
[9]Sahebkar A,Simental-Mendia LE,Guerrero-Romero F,et al.Effect of statin therapy on plasma PCSK9 concentrations:a systematic review and meta-analysis of clinical trials.Diabetes Obes Metab,2015,17:1042-55
[10]Cameron J,Ranheim T,Kulseth MA,et al.Berberine decreases PCSK9 expression in HepG2 cells.Atherosclerosis,2008,201:266-73
[11]Li H,Dong B,Park SW,et al.Hepatocyte nuclear factor 1αplays a critical role in PCSK9 gene transcription and regulation by the natural hypocholesterolemic compound berberine.J Biol Chem,2009,284:28885-95
[12]刘毅,娄少颖,何燕铭,等.小檗碱对3T3-L1前脂肪细胞增殖及分化相关基因PPARγ,C/EBPαmRNA和蛋白表达的影响.中国中西医结合杂志,2008,28:1005-9
[13]Cao SJ,Zhou Y,Xu PX,et al.Berberine metabolites exhibit triglyceride-lowering effects via activation of AMP-activated protein kinase in Hep G2 cells.JEthnopharmacol,2013,149:576-82
[14]郭晓农.小檗碱对3T3-L1脂肪细胞增殖及糖代谢的影响.中药材,2011,34:602-4
[15]Brun RP,Kim JB,Hu ED,et al.Adipocyte differentiation:a transcriptional regulatory cascade.Curr Opin Cell Biol,1996,8:826-32
[16]王树海,王文健,汪雪峰,等.黄芪多糖和小檗碱对3T3-L1脂肪细胞糖代谢及细胞分化的影响.中国中西医结合杂志,2004,24:926-8
[17]Li YJ,Zhao XM,Feng XY,et al.Berberine alleviates olanzapine-induced adipogenesis via the AMPKα-SREBPpathway in 3T3-L1 cells.Int J Mol Sci,2016,17:1865-77
[18]王宁,张娟,建方方,等.小檗碱激活AMPK抑制3T3-L1脂肪细胞分化.放射免疫学杂志,2012,25:273-5
[19]Choi YJ,Lee KY,Jung SH,et al.Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice.Toxicol Appl Pharmacol,2017,316:74-82
[20]Ma X,Egawa T,Kimura H,et al.Berberine-induced activation of 5-adenosine monophosphate-activated protein kinase and glucose transport in rat skeletal muscles.Metabolism,2010,59:1619-27
[21]Turner N,Li JY,Gosby A,et al.Berberine and its more biologically available derivative,dihydroberberine,inhibit mitochondrial respiratory complex I:a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action.Diabetes,2008,57:1414-8
[22]Lu DY,Tang CH,Chen YH,et al.Berberine suppresses neuroinflammatory responses through AMP-activated protein kinase activation bV-2 microglia.J Cell Biochem,2010,110:697-705
[23]Sun Y,Xia M,Yan H,et al.Berberine attenuates hepatic steatosis and enhances energy expenditure in mice by inducing autophagy and fibroblast growth factor 21.Br JPharmacol,2018,175:374-87
[24]Zhang X,Zhao Y,Zhang M,et al.Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats.PLoS One,2012,7:e42529
[25]Li M,Shu X,Xu H,et al.Integrative analysis of metabolome and gut microbiota in diet-induced hyperlipidemic rats treated with berberine compounds.JTransl Med,2016,14:237
[26]Guo Y,Zhang Y,Huang W,et al.Dose-response effect of berberine on bile acid profile and gut microbiota in mice.BMC Complement Altern Med,2016,16:394
[27]Cao Y,Pan Q,Cai W,et al.Modulation of gut microbiota by berberine improves steatohepatitis in high-fat diet-fed BLAB/C mice.Arch Iran Med,2016,19:197-203
[28]Aronsson L,Huang Y,Parini P,et al.Decreased fat storage by Lactobacillus paracasei is associated with increased levels of angiopoietin-like 4 protein(ANGPLT4).PLoSOne,2010,5:e13087
[29]Wang Y,Tong Q,Shou JW,et al.Gut microbiota-mediated personalized treatment of hyperlipidemia using berberine.Theranostics,2017,7:2443-51
[30]Yin J,Hu R,Chen M,et al.Effects of berberine on glucose metabolism in vitro.Metabolism,2002,51:1439-43
[31]Yin J,Xing H,Ye J.Efficacy of berberine in patients with type 2 diabetes mellitus.Metabolism,2008,57:712-7
[32]潘国宇,王广基,孙建国,等.小檗碱对葡萄糖吸收的抑制作用.药学学报,2003,38:911-4
[33]Fu D,O′Neill R A.Monosaccharide composition analysis of oligosaccharides and glycoproteins by high performance liquid chromatography.Anal Biochem,1995,227:337-84
[34]李增强.小檗碱治疗糖尿病的肠道作用靶点及分子机制研究[D].沈阳:沈阳药科大学,2012
[35]Cok A,Plaisier C,Salie MJ,et al.Berberine acutely activates the glucose transport activity of GLUT1.Biochimie,2011,93:1187-92
[36]Kim SH,Shin EJ,Kim ED,et al.Berberine activates GLUT1-mediated glucose uptake in 3T3-L1 adipocytes.Biol Pharm Bull,2007,30:2120-5
[37]Zhou L,Yang Y,Wang X,et al.Berberine stimulates glucose transport through a mechanism distinct from insulin.Metabolism,2007,56:405-12
[38]徐丽君,陆付耳,易屏,等.8-羧基二氢小檗碱改善FFA和高糖诱导的3T3-L1脂肪细胞胰岛素抵抗的作用.药学学报,2009,44:1304-8
[39]Lee YS,Kim WS,Kim KH,et al.Berberine,a natural plant product,activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulinresistant states.Diabetes,2006,55:2256-64
[40]Wu YS,Chen YT,Bao YT,et al.Identification and verification of potential therapeutic target genes in berberine-treated Zucker diabetic fatty rats through bioinformatics analysis.PLoS One,2016,11:e0166378
[41]Bai M,Liu Y,Zhou F,et al.Berberine inhibits glucose oxidation and insulin secretion in rat islets.Endocr J,2018,65:469-77
[42]Ge YB,Zhang Y,Li R,et al.Berberine regulated Gck,G6pc,Pck1 and Srebp-1c expression and activated AMP-activated protein kinase in primary rat hepatocytes.Int JBiol Sci,2011,7:673-84
[43]Dong Y,Chen YT,Yang YX,et al.Metabolomics study of type 2 diabetes mellitus and the anti-diabetic effect of berberine in zucker diabetic fatty rats using uplc-ESI-hdms.Phytother Res,2016,30:823-8
[44]Chandirasegaran G,Elanchezhiyan C,Ghosh K.Effects of berberine chloride on the liver of streptozotocin-induced diabetes in albino Wistar rats.Biomed Pharmacother,2018,99:227-36
[45]Jenkins AJ,Best JD,Klein Rl.Lipoproteins,glycoxidation and diabetic angiopathy.Diabetes Metab Res Rev,2004,20:349-68
[46]Xing LJ,Zhang L,Liu T,et al.Berberine reducing insulin resistance by up-regulating IRS-2 mRNA expression in nonalcoholic fatty liver disease(NAFLD)rat liver.Eur JPharmacol,2011,668:467-71
[47]Zhou J,Zhou S,Tang J,et al.Protective effect of berberine onβcells in streptozotocin-and high-carbohydrate/highfat diet-induced diabetic rats.Eur J Pharmacol,2009,606:262-8
[48]Wang ZQ,Lu FE,Leng SH,et al.Facilitating effects of berberine on rat pancreatic islets through modulating hepatic nuclear factor 4αexpression and glucokinase activity.World J Gastroenterol,2008,14:6004-11
[49]Gao Z,Leng S,Lu F,et al.Effect of berberine on expression of hepatocyte nuclear factor 4αin rats with fructose induced insulin resistance.J Huazhong Univ Sci Technol,2008,28:261-5
[50]Chueh WH,Lin JY.Berberine,an isoquinoline alkaloid in herbal plants,protects pancreatic islets and serum lipids in nonobese diabetic mice.J Agric Food Chem,2011,59:8021-7
[51]Chang WG.Non-coding RNAs and berberine:a new mechanism of its anti-diabetic activities.Eur J Pharmacol,2017,795:8-12
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