Preprint / Version 1

Preclinical Evidence of Berberine on Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Animal Studies

Authors

  • Sichen Ren Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
  • Xiao Ma School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
  • Ruilin Wang Integrative Medical Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
  • Honghong Liu Integrative Medical Center, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
  • Ying Wei Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
  • Shizhang Wei Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
  • Manyi Jing Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
  • Yanling Zhao Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China

Keywords:

berberine, NAFLD/NASH, meta-analysis, preclinical evidence, animal studies

Abstract

As lifestyle and diet structure impact our health, non-alcoholic fatty liver disease (NAFLD) is prevalent all over the world. Some phytomedicines containing berberine (BBR) have been extensively used for centuries in Ayurvedic and traditional Chinese medicine. The goal of this systematic review is to investigate the preclinical evidence of BBR on NAFLD models. The following relevant databases, including Web of Science, PubMed, the Cochrane Library, and Embase, were retrieved from inception to May 2021. The content involved BBR on different animal models for the treatment of NAFLD. The SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) Animal Experiment Bias Risk Assessment Tool was used to assess the methodological quality and RevMan 5.4 software was used to conduct the meta-analysis based on the Cochrane tool. A total of 31 studies involving 566 animals were included, of which five models and five animal breeds were reported. The results showed that TC, TG, ALT, AST, HDL-C, LDL-C, FBG, FINS, and FFA in the group treated with BBR were significantly restored compared with those in the model group. HOMA-IR had a significant downward trend, but the result was not significantly different (P = 0.08). The subgroup analysis of the different models and different animal breeds indicated that BBR could ameliorate the aforementioned indicator levels, although some results showed no significant difference. Finally, we summarized the molecular mechanisms by which berberine regulated NAFLD/NASH, mainly focusing on activating the AMPK pathway, improving insulin sensitivity and glucose metabolism, regulating mitochondrial function, reducing inflammation and oxidative stress, regulating cell death and ER stress, reducing DNA methylation, and regulating intestinal microenvironment and neurotoxicity. The preclinical evidence suggested that BBR might be an effective and promising drug for treating NAFLD/NASH. In addition, further studies with more well-designed researches are needed to confirm this conclusion. Keywords: berberine, NAFLD/NASH, meta-analysis, preclinical evidence, animal studies

Author Biographies

Sichen Ren, Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China

Ying Wei, Department of Pharmacy, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China

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