Efficacy of Berberine in Patients with Non-Alcoholic Fatty Liver Disease

Abstract

Objectives: A randomized, parallel controlled, open-label clinical trial was conducted to evaluate the effect of a botanic compound berberine (BBR) on NAFLD.

Methods: A randomized, parallel controlled, open-label clinical trial was conducted in three medical centers (NIH Registration number: NCT00633282). A total of 184 eligible patients with NAFLD were enrolled and randomly received (i) lifestyle intervention (LSI), (ii) LSI plus pioglitazone (PGZ) 15mg qd, and (iii) LSI plus BBR 0.5g tid, respectively, for 16 weeks. Hepatic fat content (HFC), serum glucose and lipid profiles, liver enzymes and serum and urine BBR concentrations were assessed before and after treatment. We also analyzed hepatic BBR content and expression of genes related to glucose and lipid metabolism in an animal model of NAFLD treated with BBR.

Results: As compared with LSI, BBR treatment plus LSI resulted in a significant reduction of HFC (52.7% vs 36.4%, p = 0.008), paralleled with better improvement in body weight, HOMA-IR, and serum lipid profiles (all p<0.05). BBR was more effective than PGZ 15mg qd in reducing body weight and improving lipid profile. BBR-related adverse events were mild and mainly occurred in digestive system. Serum and urine BBR concentrations were 6.99ng/ml and 79.2ng/ml, respectively, in the BBR-treated subjects. Animal experiments showed that BBR located favorably in the liver and altered hepatic metabolism-related gene expression.

Conclusion: BBR ameliorates NAFLD and related metabolic disorders. The therapeutic effect of BBR on NAFLD may involve a direct regulation of hepatic lipid metabolism.

Trial registration: ClinicalTrials.gov NCT00633282.

Fig 1. CONSORT Flow Diagram.

184 subjects were assigned to receive lifestyle intervention alone (n = 62), lifestyle intervention plus pioglitazone (n = 60), and lifestyle intervention plus berberine (n = 62). At the end of therapy, 53, 47 and 55 subjects in the three groups completed the follow-up visit, respectively.

Fig 2. Reduction of blood glucose, body weight and hepatic fat content after therapy.

Mean values are shown for percentage changes from baseline of A) FBG, B) PBG, C) body weight and D) The mean HFC of the three groups before and after treatment. *p<0.05, compared with LSI group, &p<0.05, comared with LSI plus PGZ group.

Fig 3. Comparison of HFC decrease (%) between the LSI and LSI plus BBR groups at different degrees of body weight change (<5%, 5–10% and ≥10% body weight change).

*p<0.05, compared with the LSI group with the same degree of weight loss.

Fig 4. Concentration of BBR and its metabolites (M1, M2, M3, M4) in HFD rat liver and plasma (Mean ± SEM, n = 6).

Fig 5

A-E) Altered expression of genes closely related to glucose and lipid metabolism in liver of SD rats. The samples were examined within 48h after single-dosing of BBR in oral route. Real-time quantitative PCR was used to detect the liver A) MTTP, B) CPT-1α, C) GCK, D) LDLR and E) LPK mRNA expression at different time courses. F) Quantification of the MTTP, CPT-1, C) GCK, D) LDLR and E) LPK mRNAes were examined within 48h after single-dosing of BBR in oral route. liMTTP, microsomal triglyceride transfer protein; CPT-1α, carnitine palmitoyltransferase-1α; GCK, glucokinase; LDLR, low density lipoprotein receptor; LPK, liver pyruvate kinase.