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Combination of Berberine with Resveratrol Improves the Lipid-Lowering Efficacy.

ABSTRACT: The natural compound berberine has been reported to exhibit anti-diabetic activity and to improve disordered lipid metabolism. In our previous study, we found that such compounds upregulate expression of sirtuin 1-a key molecule in caloric restriction, it is, therefore, of great interest to examine the lipid-lowering activity of berberine in combination with a sirtuin 1 activator resveratrol. Our results showed that combination of berberine with resveratrol had enhanced hypolipidemic effects in high fat diet-induced mice and was able to decrease the lipid accumulation in adipocytes to a level significantly lower than that in monotherapies. In the high fat diet-induced hyperlipidemic mice, combination of berberine (30 mg/kg/day, oral) with resveratrol (20 mg/kg/day, oral) reduced serum total cholesterol by 27.4% ± 2.2%, and low-density lipoprotein-cholesterol by 31.6% ± 3.2%, which was more effective than that of the resveratrol (8.4% ± 2.3%, 6.6% ± 2.1%) or berberine (10.5% ± 1.95%, 9.8% ± 2.58%) monotherapy (p < 0.05 for both). In 3T3-L1 adipocytes, the treatment of 12 µmol/L or 20 µmol/L berberine combined with 25 µmol/L resveratrol showed a more significant inhibition of lipid accumulation observed by Oil red O stain compared with individual compounds. Moreover, resveratrol could increase the amount of intracellular berberine in hepatic L02 cells. In addition, the combination of berberine with resveratrol significantly increases the low-density-lipoprotein receptor expression in HepG2 cells to a level about one-fold higher in comparison to individual compound. These results implied that the enhanced effect of the combination of berberine with resveratrol on lipid-lowering may be associated with upregulation of low-density-lipoprotein receptor, and could be an effective therapy for hyperlipidemia in some obese-associated disease, such as type II diabetes and metabolic syndrome.

SUBMITTER: Zhu X

PROVIDER: S-EPMC6321535 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Combination of Berberine with Resveratrol Improves the Lipid-Lowering Efficacy.

Zhu Xiaofei X Yang Jingyi J Zhu Wenjuan W Yin Xiaoxiao X Yang Beibei B Wei Yihui Y Guo Xiaofang X

International journal of molecular sciences 20181206 12

The natural compound berberine has been reported to exhibit anti-diabetic activity and to improve disordered lipid metabolism. In our previous study, we found that such compounds upregulate expression of sirtuin 1-a key molecule in caloric restriction, it is, therefore, of great interest to examine the lipid-lowering activity of berberine in combination with a sirtuin 1 activator resveratrol. Our results showed that combination of berberine with resveratrol had enhanced hypolipidemic effects in ...[more]

PMID: 30563192

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Project description:BackgroundZhibitai, a natural lipid-lowering Chinese medicine, is well tolerated in patients and has low incidence of adverse events. In this study, we evaluated the efficacy, safety, and side effects of Zhibitai in combination with low dose Atorvastatin compared to high dose Atorvastatin in patients with coronary heart disease or at high risk of coronary heart disease.MethodsThis was a randomized, double-blind, multi-center clinical trial on 720 patients with coronary heart disease or at high risk of coronary heart disease. The patients were randomly assigned to a Zhibitai-Atorvastatin group (480 mg Zhibitai twice daily plus 10 mg atorvastatin once daily) or Monotherapy group (40 mg Atorvastatin once daily). Blood samples were obtained at baseline, week 4, and week 8 after a minimum 8-hour fast. Efficacy was evaluated in terms of the changes in the following parameters: lipoprotein profiles [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)]. Safety was assessed throughout the study by clinical laboratory tests including liver function [alanine transaminase, aspartate transaminase] and renal function [blood urea nitrogen], and creatine kinase; physical examination; and adverse events monitoring.ResultsTC, TG, LDL-C levels were significantly decreased andHDL-C levels were significantly increased at week 4 and week 8 (all P < 0.05) in both groups but had no significant differences between the two groups (P > 0.05). In subgroup analyses, Zhibitai-Atorvastatin Group produced significantly greater reduction in TG compared with Monotherapy Group at week 8 in patients with TG > 203.72mg/dL (P < 0.01). Among patients with LDL-C levels > 131.48 mg/dL, Zhibitai-Atorvastatin Group produced a greater reduction of LDL-C levels compared with the Monotherapy Group at week 4 (P < 0.05). The incidence of liver dysfunction, headache, or gastrointestinal intolerance was significantly lower in the Zhibitai-Atorvastatin Group compared with Monotherapy Group during the 8-week study peroid (P < 0.001). There were no significant differences in renal function, myopathy, and other adverse events between the groups.ConclusionOverall the two groups have similar lipid regulation efficacy. Zhibitai plus low dose Atorvastatin is more efficacious in lowering TG in patients with TG > 203.72 mg/dL at week 8. There are fewer side effects in Zhibitai plus low dose Atorvastatin group. Long term follow up is required to evaluate cardiovascular outcomes.

Project description:Statins are the frontline in cholesterol reduction therapies; however, their use in combination with agents that possess complimentary mechanisms of action may achieve further reductions in low-density lipoprotein cholesterol. Thirty-nine patients were treated with either 80 mg simvastatin (n=20) or 10 mg simvastatin plus 10 mg ezetimibe (n=19) for 6 weeks. Dosing was designed to produce comparable low-density lipoprotein cholesterol reductions, while enabling assessment of potential simvastatin-associated pleiotropic effects. Baseline and post-treatment plasma were analyzed for lipid mediators (eg, eicosanoids and endocannabinoids) and structural lipids by liquid chromatography tandem mass spectrometry. After statistical analysis and orthogonal projections to latent structures multivariate modeling, no changes were observed in lipid mediator levels, whereas global structural lipids were reduced in response to both monotherapy (R(2)Y=0.74; Q(2)=0.66; cross-validated ANOVA P=7.0×10(-8)) and combination therapy (R(2)Y=0.67; Q(2)=0.54; cross-validated ANOVA P=2.6×10(-5)). Orthogonal projections to latent structures modeling identified a subset of 12 lipids that classified the 2 treatment groups after 6 weeks (R(2)Y=0.65; Q(2)=0.61; cross-validated ANOVA P=5.4×10(-8)). Decreases in the lipid species phosphatidylcholine (15:0/18:2) and hexosyl-ceramide (d18:1/24:0) were the strongest discriminators of low-density lipoprotein cholesterol reductions for both treatment groups (q<0.00005), whereas phosphatidylethanolamine (36:3e) contributed most to distinguishing treatment groups (q=0.017). Shifts in lipid composition were similar for high-dose simvastatin and simvastatin/ezetimibe combination therapy, but the magnitude of the reduction was linked to simvastatin dosage. Simvastatin therapy did not affect circulating levels of lipid mediators, suggesting that pleiotropic effects are not associated with eicosanoid production. Only high-dose simvastatin reduced the relative proportion of sphingomyelin and ceramide to phosphatidylcholine (q=0.008), suggesting a pleiotropic effect previously associated with a reduced risk of cardiovascular disease.

Project description:BackgroundLipids are ubiquitous metabolites with diverse functions. Excessive lipid accumulation can trigger lipid redistribution among metabolic organs such as adipose, liver and muscle, thus altering the lipid metabolism. It has been revealed that disturbed lipid metabolism would cause multiple disease complications and is highly correlated with human morbidity. Resveratrol (RSV), a phytoestrogen with antioxidant, can modulate insulin resistance and lipid profile. Recently, research on RSV supplementation to improve glucose and lipid metabolism has been controversial. A meta-analysis may provide a scientific reference for the relationship between lipid metabolism and RSV supplementation.Methods and analysisWe searched the PubMed, Cochrane Library, Web of Science, and Embase databases from inception to October 2021 using relevant keywords. A comprehensive search for randomized controlled trials (RCTs) was performed. For calculating pooled effects, continuous data were pooled by mean difference (MD) and 95% confidence interval (CI). Adopting the method of inverse-variance with a random-effect, all related statistical analyses were performed using the Rev Man V.5.3 and STATA V.15 software.ResultsA total of 25 articles were incorporated into the final meta-analysis after removal of duplicates by checking titles and abstracts and excluding non-relevant articles. The selected articles had a total of 1,171 participants, including 578 in the placebo group and 593 in the intervention group. According to the current meta-analysis, which demonstrated that there was a significant decrease in waist circumference (SMD = -0.36; 95% CI: -0.59, -0.14; P = 0.002; I 2 = 88%), hemoglobin A1c (-0.48; -0.69, -0.27; P ≤ 0.001; I 2 = 94%), total cholesterol (-0.15; -0.3, -0.01; P = 0.003; I 2 = 94%), low density lipoprotein cholesterol (-0.42; -0.57, -0.27; P ≤ 0.001; I 2 = 92%), high density lipoprotein cholesterol (0.16; -0.31, -0.02; P = 0.03; I 2 = 81%) following resveratrol administration.ConclusionThese results suggest that RSV has a dramatic impact on regulating lipid and glucose metabolism, and the major clinical value of resveratrol intake is for obese and diabetic patients. We hope that this study could provide more options for clinicians using RSV. Furthermore, in the future, large-scale and well-designed trials will be warranted to confirm these results.Systematic review registrationWebsite [https://www.crd.york.ac.uk/prospero/#recordDetails], identifier [CRD42021244904].

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Combination of Berberine with Resveratrol Improves the Lipid-Lowering Efficacy.

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Combination of Berberine with Resveratrol Improves the Lipid-Lowering Efficacy.

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