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DOI: 10.1055/s-0035-1568261
Hypolipidemic Effects of Alkaloids from Rhizoma Coptidis in Diet-Induced Hyperlipidemic Hamsters
Publication History
received 04 March 2015
revised 16 December 2015
accepted 17 December 2015
Publication Date:
05 February 2016 (online)
Abstract
This study was conducted to evaluate the antihyperlipidemic activity of five major alkaloids in Rhizoma Coptidis using high-fat- and high-cholesterol-induced hyperlipidemic hamsters. Hyperlipidemic hamsters were treated with coptisine, berberine, jatrorrhizine, palmatine, epiberberine, and total Rhizoma Coptidis alkaloids with a dose of 46.7 mg/kg × day for 140 days. Serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total bile acids were examined after alkaloid treatment. The results showed that all therapy agents prevented body weight gain, reduced the serum total cholesterol, and increased the high-density lipoprotein cholesterol of hamsters. Berberine, jatrorrhizine, and total Rhizoma Coptidis alkaloids decreased the triglyceride level in hyperlipidemic hamsters, while coptisine, jatrorrhizine, palmatine, and total Rhizoma Coptidis alkaloids significantly suppressed the elevation of the low-density lipoprotein cholesterol level. The fecal excretion of bile acids was significantly elevated by berberine, coptisine, jatrorrhizine, palmatine, total Rhizoma Coptidis alkaloids, and orlistat. Notably, total Rhizoma Coptidis alkaloids possess a much stronger lipid-lowering effect than the pure Rhizoma Coptidis alkaloids. Quantitative reverse transcription-polymerase chain reaction analyses revealed that Rhizoma Coptidis alkaloids could retard the synthesis of cholesterol by downregulating the mRNA expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase and accelerate the clearance of lipids by upregulating the low-density lipoprotein receptor, cholesterol 7α-hydroxylase, and uncoupling protein-2 expression. These findings highlight the critical role of Rhizoma Coptidis alkaloids in hyperlipidemia treatment. Thus, they need to be considered in future therapeutic approaches.
Key words
Rhizoma Coptidis - Ranunculaceae - alkaloids - hyperlipidemic hamsters - antihyperlipidemic - mechanism-
References
- 1 Yan W. Efficiency comparison of aerobic exercise combination of stomach muscle training in abdominal obesity individual. Chinese J Gerontol 2015; 2: 477-479
- 2 Genest J, Mcpherson R, Frohlich J, Anderson T, Campbell N, Carpentier A, Couture P, Dufour R, Fodor G, Francis GA, Grover S, Gupta M, Hegele RA, Lau DC, Leiter L, Lewis GF, Lonn E, Mancini GB, Ng D, Pearson GJ, Sniderman A, Stone JA, Ur E. 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult – 2009 recommendations. Can J Cardiol 2009; 25: 567-579
- 3 Liu HH, Li JJ. Aging and dyslipidemia: a review of potential mechanisms. Ageing Res Rev 2015; 19: 43-52
- 4 Li ZY, Yang RF, Xu GB, Xia T. Serum lipid concentrations and prevalence of dyslipidemia in a large professional population in Beijing. Clin Chem 2005; 51: 144-150
- 5 Manickam P, Rathod A, Panaich S, Hari P, Veeranna V, Badheka A, Jacob S, Afonso L. Comparative prognostic utility of conventional and novel lipid parameters for cardiovascular disease risk prediction: do novel lipid parameters offer an advantage?. J Clin Lipidol 2011; 5: 82-90
- 6 Ioannides-Demos LL, Piccenna L, Mcneil JJ. Pharmacotherapies for obesity: past, current, and future therapies. J Obes 2011; 2011: 179674
- 7 Group UDS. U.K. Prospective Diabetes Study 27. Plasma lipids and lipoproteins at diagnosis of NIDDM by age and sex. Diabetes Care 1997; 20: 1683-1687
- 8 Ikeda H, Taketomi S, Sugiyama Y, Shimura Y, Sohda T, Meguro K, Fujita T. Effects of pioglitazone on glucose and lipid metabolism in normal and insulin resistant animals. Arzneimittelforsch 1990; 40: 156-162
- 9 Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, Wang Y, Wang Z, Si S, Pan H, Wang S, Wu J, Wang Y, Li Z, Liu J, Jiang JD. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med 2004; 10: 1344-1351
- 10 Hu Y, Ehli EA, Kittelsrud J, Ronan PJ, Munger K, Downey T, Bohlen K, Callahan L, Munson V, Jahnke M, Marshall L, Nelson K, Huizenga P, Hansen R, Soundy T, Davies GE. Lipid-lowering effect of berberine in human subjects and rats. Phytomedicine 2012; 19: 861-867
- 11 Lee YS, Kim WS, Kim KH, Yoon MJ, Cho HJ, Shen Y, Ye JM, Lee CH, Oh WK, Kim CT, Behrens CH, Gosby A, Kraegen EW, James DE, Kim JB. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes 2006; 55: 2256-2264
- 12 Brusq JM, Ancellin N, Grondin P, Guillard R, Martin S, Saintillan Y, Issandou M. Inhibition of lipid synthesis through activation of AMP kinase: an additional mechanism for the hypolipidemic effects of berberine. J Lipid Res 2006; 47: 1281-1288
- 13 Hui D, Yan Z, Li Z, Fuer L. The effects of berberine on blood lipids: a systemic review and meta-analysis of randomized controlled trials. Planta Med 2013; 79: 437-446
- 14 Kahlon T, Chow F, Knuckles B, Chiu M. Cholesterol-lowering effects in hamsters of b-glucan-enriched barley fraction, dehulled whole barley, rice bran, and oat bran and their combinations. Cereal Chem 1993; 70: 435-440
- 15 Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a metaanalysis of population-based prospective studies. J Cardiovasc Risk 1996; 3: 213-219
- 16 Assmann G, Schulte H. Relation of high-density lipoprotein cholesterol and triglycerides to incidence of atherosclerotic coronary artery disease (the PROCAM experience). Am J Cardiol 1992; 70: 733-737
- 17 Brehm BJ, Seeley RJ, Daniels SR, DʼAlessio DA. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab 2003; 88: 1617-1623
- 18 Bartness TJ, Wade GN. Photoperiodic control of seasonal body weight cycles in hamsters. Neurosci Biobehav Rev 1985; 9: 599-612
- 19 Haerer W, Delbaere K, Bartlett H, Lord S, Rowland J. Relationships between HMG‐CoA reductase inhibitors (statin) use and strength, balance and falls in older people. Intern Med J 2012; 42: 1329-1334
- 20 Notarnicola M, Messa C, Refolo MG, Tutino V, Miccolis A, Caruso MG. Synergic effect of eicosapentaenoic acid and lovastatin on gene expression of HMGCoA reductase and LDL receptor in cultured HepG2 cells. Lipids Health Dis 2010; 9: 135-143
- 21 Han H, Xin P, Zhao L, Xu J, Xia Y, Yang X. Excess iodine and high-fat diet combination modulates lipid profile, thyroid hormone, and hepatic LDLr expression values in mice. Biol Trace Elem Res 2012; 147: 233-239
- 22 Chen Q, Wang E, Ma L, Zhai P. Dietary resveratrol increases the expression of hepatic 7α-hydroxylase and ameliorates hypercholesterolemia in high-fat fed C57BL/6 J mice. Lipids Health Dis 2012; 11: 56-63
- 23 Chiang JYL. Bile acids: regulation of synthesis. J Lipid Res 2009; 50: 1955-1966
- 24 Lan T, Rao A, Haywood J, Kock ND, Dawson PA. Mouse organic solute transporter alpha deficiency alters FGF15 expression and bile acid metabolism. J Hepatol 2012; 57: 359-365
- 25 Walters JR, Tasleem AM, Omer OS, Brydon WG, Dew T, le Roux CW. A new mechanism for bile acid diarrhea: defective feedback inhibition of bile acid biosynthesis. Clin Gastroenterol Hepatol 2009; 7: 1189-1194
- 26 Out C, Patankar JV, Doktorova M, Boesjes M, Bos T, de Boer S, Havinga R, Wolters H, Boverhof R, van Dijk TH, Smoczek A, Bleich A, Sachdev V, Kratky D, Kuipers F, Verkade HJ, Groen AK. Gut microbiota inhibit Asbt-dependent intestinal bile acid reabsorption via Gata4. J Hepatol 2015; 63: 697-704
- 27 Divakaruni AS, Brand MD. The regulation and physiology of mitochondrial proton leak. Physiology (Bethesda) 2011; 26: 192-205
- 28 Mailloux RJ, Harper ME. Uncoupling proteins and the control of mitochondrial reactive oxygen species production. Free Radic Biol Med 2011; 51: 1106-1115
- 29 Oktavianthi S, Trimarsanto H, Febinia CA, Suastika K, Saraswati MR, Dwipayana P, Arindrarto W, Sudoyol H, Malik SG. Uncoupling protein 2 gene polymorphisms are associated with obesity. Cardiovasc Diabetol 2012; 11: 41-51
- 30 Oh K, Kim M, Lee J, Kim M, Nam Y, Ham J. Liver PPARalpha and UCP2 are involved in the regulation of obesity and lipid metabolism by swim training in genetically obese db/db mice. Biochem Biophys Res Commun 2006; 345: 1232-1239
- 31 Harper ME, Dent R, Monemdjou S, Bézaire V, Van WL, Wells G, Kavaslar GN, Tesson F, McPherson R. Decreased mitochondrial proton leak and reduced expression of uncoupling protein 3 in skeletal muscle of obese diet-resistant women. Diabetes 2002; 51: 2459-2466
- 32 Faggioni R, Shigenaga J, Moser A, Feingold KR, Grunfeld C. Induction of UCP2 gene expression by LPS: a potential mechanism for increased thermogenesis during infection. Biochem Biophys Res Commun 1998; 244: 75-78
- 33 Jung HA, Min BS, Yokozawa T, Lee JH, Kim YS, Choi JS. Anti-Alzheimer and antioxidant activities of Coptidis Rhizoma alkaloids. Biol Pharm Bull 2009; 32: 1433-1438
- 34 Wang L, Ye X, Li X, Chen Z, Chen X, Gao Y, Zhao Z, Huang W, Chen X, Yi J. [Metabolism, transformation and distribution of Coptis chinensis total alkaloids in rat]. China J Chinese Materia Med (Zhongguo Zhong Yao Za Zhi) 2010; 35: 2017-2020
- 35 Yu S, Yu Y, Liu L, Wang X, Lu S, Liang Y, Liu X, Xie L, Wang G. Increased plasma exposures of five protoberberine alkaloids from Coptidis Rhizoma in streptozotocin-induced diabetic rats: is P-GP Involved?. Planta Med 2010; 76: 876-881
- 36 Kim HS, Kim MJ, Kim EJ, Yang Y, Lee MS, Lim JS. Berberine-induced AMPK activation inhibits the metastatic potential of melanoma cells via reduction of ERK activity and COX-2 protein expression. Biochem Pharmacol 2012; 83: 385-394
- 37 Jiang Q, Liu P, Wu X, Liu W, Shen X, Lan T, Xu S, Peng J, Xie X, Huang H. Berberine attenuates lipopolysaccharide-induced extracelluar matrix accumulation and inflammation in rat mesangial cells: involvement of NF-κB signaling pathway. Mol Cell Endocrinol 2011; 331: 34-40
- 38 Sangeetha M, Priya C, Vasanthi HR. Anti-diabetic property of Tinospora cordifolia and its active compound is mediated through the expression of Glut-4 in L6 myotubes. Phytomedicine 2013; 20: 246-248
- 39 Chen HY, Ye XL, Cui XL, He K, Jin YN, Chen Z. Cytotoxicity and antihyperglycemic effect of minor constituents from Rhizoma Coptis in HepG2 cells. Fitoterapia 2012; 83: 67-73
- 40 Monte MJ, El-Mir MY, Sainz GR, Bravo P, Marin JG. Bile acid secretion during synchronized rat liver regeneration. Biochim Biophys Acta 1997; 1362: 56-66
- 41 Laura CB, Noemí R, Catherine F, Rosa R, Francisco BV, Joan C. Liver X receptor-mediated activation of reverse cholesterol transport from macrophages to feces in vivo requires ABCG5/G8. J Lipid Res 2008; 49: 904-911
- 42 Barber RD, Harmer DW, Coleman RA, Clark BJ. GAPDH as a housekeeping gene: analysis of GAPDH mRNA expression in a panel of 72 human tissues. Physiol Genomics 2005; 21: 389-395