Abstract
The present study was conducted to determine the efficacy and underlying mechanism
of berberine (BBR), plant stanols (PS) and their combination on plasma lipids. Male
Golden Syrian hamsters were randomly divided into 4 groups (n = 15/group) and fed a cornstarch–casein–sucrose-based diet containing 0.15% cholesterol
and 5% fat. Three treatment groups were supplemented with 0.17% (equivalent to 100 mg kg−1 d−1) BBR, 1% PS, or a combination of both (BBRPS) for 4 wk. At the end of the study, plasma lipids were analyzed with enzymatic methods, cholesterol
absorption and synthesis using stable isotope tracer methodology, and gene and protein
expressions in the liver and small intestine using real-time PCR and Western blot,
respectively. BBR and PS significantly lowered plasma total- and nonHDL-cholesterol
levels, and BBRPS markedly improved cholesterol-lowering efficacy compared to BBR
or PS alone. Further examinations revealed that BBR and PS both inhibited cholesterol
absorption and by contrast, increased cholesterol synthesis, and exerted a synergistic
action when they were combined. Plasma total or nonHDL-cholesterol levels were significantly
correlated with cholesterol absorption rates. BBR upregulated sterol 27-hydroxlase
gene expression and BBRPS increased both cholesterol-7α-hydroxylase and sterol 27-hydroxlase
gene expressions. BBR and PS also synergistically decreased plasma triacylglycerides.
These findings suggest that the cholesterol-lowering action of BBR might involve a
combination of inhibition of cholesterol absorption and stimulation of bile acid synthesis.
The combination of BBR and PS improves cholesterol-lowering efficacy through a synergistic
action on cholesterol absorption, in addition to synergistically reducing plasma triacylglycerols
in hamsters.
Abbreviations:
ABCG (ATP-binding cassette superfamily G), BBR (berberine chloride), BBRPS (combination of BBR and plant stanols), BW (body weight), CT (control), FSR (free cholesterol fractional synthesis rate), CYP7A1 (cholesterol-7α-hydroxylase), CYP27A1 (sterol 27-hydroxlase), GAPDH (glyceraldehyde 3-phosphate dehydrogenase), GC (gas chromatography), GC/C/IRMS (gas chromatography/combustion/isotope ratio mass spectrometer), GC/P/IRMS (gas chromatography/pyrolysis/isotope ratio mass spectrometer), HDL-C (HDL-cholesterol), IRMS (isotope ratio mass spectrometer), LDL-C (LDL-cholesterol), LDLR (LDL-receptor), nonHDL-C (nonHDL-cholesterol (very low density lipoprotein cholesterol+intermediate density lipoprotein cholesterol+LDL-cholesterol)), NPC1L1 (Niemann-Pick C1 Like 1), PS (plant stanols), TAG (triacylglycerol), T-C (total cholesterol)Keywords
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References
- Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.Am J Cardiol. 2003; 92: 173-176
- Effect of Alstonia scholaris in enhancing the anticancer activity of berberine in the Ehrlich ascites carcinoma-bearing mice.J Med Food. 2004; 7: 235-244
- Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins.Nat Med. 2004; 10: 1344-1351
- Eulipidemic effects of berberine administered alone or in combination with other natural cholesterol-lowering agents. A single-blind clinical investigation.Arzneimittelforschung. 2007; 57: 26-30
- The medicinal plant goldenseal is a natural LDL-lowering agent with multiple bioactive components and new action mechanisms.J Lipid Res. 2006; 47: 2134-2147
- Effects of berberine on diabetes induced by alloxan and a high-fat/high-cholesterol diet in rats.J Ethnopharmacol. 2006; 108: 109-115
- Unesterified plant sterols and stanols lower LDL-cholesterol concentrations equivalently in hypercholesterolemic persons.Am J Clin Nutr. 2002; 76: 1272-1278
- Soy protein reduces triglyceride levels and triglyceride fatty acid fractional synthesis rate in hypercholesterolemic subjects.Atherosclerosis. 2004; 173: 269-275
- Dietary fibre, lente carbohydrates and the insulin-resistant diseases.Br J Nutr. 2000; 83: S157-S163
- The role of statins in clinical medicine – LDL – cholesterol lowering and beyond.Swiss Med Wkly. 2006; 136: 41-49
- Pharmacology and applications of chinese materia medica.World Scientific Publishing Co. Pte. Ltd., Farrer Road, Singapore2000 (p. 60)
- Effect of berberine on bile secretion.Nihon Univ J Med. 1974; 16: 69-79
- Choleretic action of berberine Sb Nauchn Tr Vladivostoksk.Med Inst. 1964; 2: 113-115
- Interaction of liposomes with homologous series of fluorescent berberine derivatives. New cationic probes for measuring membrane potential.Biochim Biophys Acta. 1981; 640: 341-351
- Berberine alkaloid as a sensitive fluorescent probe for bile salt aggregates.J Phys Chem B. 2007; 111: 5635-5639
- Serum, biliary, and fecal cholesterol and plant sterols in colectomized patients before and during consumption of stanol ester margarine.Am J Clin Nutr. 2000; 71: 1095-1102
- Safety aspects and cholesterol-lowering efficacy of low fat dairy products containing plant sterols.Eur J Clin Nutr. 2006; 60: 633-642
- Co-administration of berberine and plant stanols synergistically reduces plasma cholesterol in rats.Atherosclerosis. 2008;
- Animal models of human lipid metabolism.Prog Lipid Res. 1993; 32: 1-24
- AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet.J Nutr. 1993; 123: 1939-1951
- Gender effects of tall oil versus soybean phytosterols as cholesterol-lowering agents in hamsters.Can J Physiol Pharmacol. 1998; 76: 780-787
- Effects of policosanols and phytosterols on lipid levels and cholesterol biosynthesis in hamsters.Lipids. 2003; 38: 165-170
- Design criteria for studies examining individual fatty acid effects on cardiovascular disease risk factors: human and animal studies.Am J Clin Nutr. 1997; 65: 1590S-1596S
- Dietary sitostanol reciprocally influences cholesterol absorption and biosynthesis in hamsters and rabbits.Atherosclerosis. 1999; 143: 341-351
- Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.Clin Chem. 1972; 18: 499-502
- Hypocholesterolaemic effects of plant sterol analogues are independent of ABCG5 and ABCG8 transporter expressions in hamsters.Br J Nutr. 2007; 98: 550-555
- Stanol esters decrease plasma cholesterol independently of intestinal ABC sterol transporters and Niemann-Pick C1-Like 1 protein gene expression.J Lipid Res. 2004; 45: 2252-2259
- Function and regulation of hydroxylases involved in the bile acid biosynthesis pathways.Semin Liver Dis. 1992; 12: 403-419
- Selective inhibition of CYP27A1 and of chenodeoxycholic acid synthesis in cholestatic hamster liver.Biochim Biophys Acta. 2002; 1588: 139-148
- The ABC of hepatic and intestinal cholesterol transport.Handbook Exp Pharmacol. 2005; : 465-482
- Reduction of cholesterol absorption by dietary plant sterols and stanols in mice is independent of the Abcg5/8 transporter.J Nutr. 2006; 136: 2135-2140
- Changes in intestinal and liver global gene expression in response to a phytosterol-enriched diet.Atherosclerosis. 2005; 181: 75-85
- Cholesterol absorption efficiency regulates plasma cholesterol level in the Finnish population.Eur J Clin Invest. 1987; 17: 391-395
- Effects of chenodeoxycholic acid and deoxycholic acid on cholesterol absorption and metabolism in humans.Transl Res. 2006; 148: 37-45
- Alterations in cholesterol absorption and synthesis characterize Framingham offspring study participants with coronary heart disease.J Lipid Res. 2009;
- Dietary plant stanol esters reduce VLDL cholesterol secretion and bile saturation in apolipoprotein E*3-Leiden transgenic mice.Arterioscler Thromb Vasc Biol. 2001; 21: 1046-1052
- Delineation of molecular changes in intrahepatic cholesterol metabolism resulting from diminished cholesterol absorption.J Lipid Res. 2005; 46: 779-789
- Pharmacology and therapeutics of ezetimibe (SCH 58235), a cholesterol-absorption inhibitor.Clin Ther. 2003; 25: 2352-2387
- Ezetimibe, a potent cholesterol absorption inhibitor, normalizes combined dyslipidemia in obese hyperinsulinemic hamsters.Diabetes. 2001; 50: 1330-1335
- Results of phase 1/II clinical trials with ezetimibe, a novel selective cholesterol absorption inhibitor.Eur Heart J. 2001; 3: E11-E16
- The molecular mechanisms underlying the reduction of LDL apoB-100 by ezetimibe plus simvastatin.J Lipid Res. 2007; 48: 699-708
- Effects of variable dietary sitostanol concentrations on plasma lipid profile and phytosterol metabolism in hamsters.Biochim Biophys Acta. 1998; 1390: 237-244
- Very long chain fatty acids (policosanols) and phytosterols affect plasma lipid levels and cholesterol biosynthesis in hamsters.Metabolism. 2005; 54: 508-514
- Triglyceride as a risk factor for ischaemic heart disease in British men: effect of adjusting for measurement error.Atherosclerosis. 1999; 143: 275-284
- Pro and con: high-density lipoprotein, triglycerides, and other lipid subfractions are the future of lipid management.Am J Cardiol. 2001; 87: 2B-7B
- 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
- 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
Article info
Publication history
Published online: September 27, 2009
Accepted:
August 25,
2009
Received in revised form:
August 10,
2009
Received:
July 11,
2009
Identification
Copyright
© 2009 Published by Elsevier Inc. All rights reserved.
