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

PLoS One. 2015 Aug 7;10(8):e0134172. doi: 10.1371/journal.pone.0134172. eCollection 2015.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / drug effects
  • Adiposity / genetics
  • Administration, Oral
  • Animals
  • Berberine / adverse effects
  • Berberine / blood
  • Berberine / pharmacology
  • Berberine / therapeutic use*
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diet, High-Fat
  • Disease Models, Animal
  • Energy Metabolism / drug effects
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Liver / drug effects
  • Liver / enzymology
  • Liver / pathology
  • Male
  • Metabolome / drug effects
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / blood
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / genetics
  • Phenotype
  • Rats, Sprague-Dawley
  • Treatment Outcome

Substances

  • Blood Glucose
  • Berberine

Associated data

  • ClinicalTrials.gov/NCT00633282

Grant support

This work was supported by grants from the Major State Basic Research Development Program of China (2012CB524906 to Gao X.; http://www.973.gov.cn/Default_3.aspx), National Natural Science Foundation of China (81270933 to Gao X.), Major State Basic Research Development Program of China (2011CB504004 to Gao X.), the Science and Technology Commission of Shanghai Municipality (07JC14011 to Gao X.), the National Ministry of Education Program (985 III-YFX0302 to Gao X.) and Shanghai Municipal Health Bureau Foundation (12GWZX0103 to Gao X.), National Natural Science Foundation of China for Young Scholar (81200627 to Yan HM., 81100602 to Chang XX., 81300682 to Xia MF.), Foundation of Fudan University, China (20520133483 to Yan HM., 20520133383 to Chang XX.).