Terminalia bellirica ethanol extract ameliorates nonalcoholic fatty liver disease in mice by amending the intestinal microbiota and faecal metabolites

Boyu Zhang; Xiaomin Luo; Cairong Han; Jingxian Liu; Le Zhang; Jin Qi; Jian Gu; Rui Tan; Puyang Gong

doi:10.1016/j.jep.2022.116082

Terminalia bellirica ethanol extract ameliorates nonalcoholic fatty liver disease in mice by amending the intestinal microbiota and faecal metabolites

J Ethnopharmacol. 2023 Apr 6:305:116082. doi: 10.1016/j.jep.2022.116082. Epub 2022 Dec 27.

Authors

Boyu Zhang¹, Xiaomin Luo¹, Cairong Han¹, Jingxian Liu¹, Le Zhang¹, Jin Qi², Jian Gu¹, Rui Tan³, Puyang Gong⁴

Affiliations

¹ College of Pharmacy, Southwest Minzu University, Chengdu, 610041, China.
² Research Center for Traceability and Standardization of TCMs, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
³ College of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China.
⁴ College of Pharmacy, Southwest Minzu University, Chengdu, 610041, China. Electronic address: gongpuyang1990@163.com.

PMID: 36581163
DOI: 10.1016/j.jep.2022.116082

Abstract

Ethnopharmacological relevance: Terminalia bellirica (Gaertn.) Roxb. (TB) is a traditional Tibetan medicine used to treat hepatobiliary diseases. However, modern pharmacological evidence of the activities and potential mechanisms of TB against nonalcoholic fatty liver disease (NAFLD) are still unknown.

Aim of the study: This study aimed to evaluate the anti-NAFLD effect of ethanol extract of TB (ETB) and investigate whether its ameliorative effects are associated with the regulation of intestinal microecology.

Materials and methods: In this study, the curative effects of ETB on NAFLD were evaluated in mice fed a choline-deficient, L-amino acid defined, high fat diet (CDAHFD). Biochemical markers and hepatic histological alterations were detected. Gut microbiota and faecal metabolites were analyzed by 16S rRNA gene sequencing and liquid chromatograph mass spectrometer (LC‒MS) profiling.

Results: The results showed that oral treatment with middle- and high-dose ETB significantly improved features of NAFLD, reducing the levels of TG, LDL-C, ALT and AST, and increasing the level of HDL-C. Liver histopathologic examination demonstrated that ETB attenuated lipid accumulation and hepatocellular necrosis. ETB treatment restored the structural disturbances of gut microbiota induced by CDAHFD, reduced the levels of Intestinimonas, Lachnoclostridium, and Lachnospirace-ae_FCS020_group, and increased Akkermansia and Bifidobacterium. Moreover, untargeted metabolomics analysis revealed that ETB could restore the disrupted taurine and hypotaurine metabolism, glycine, serine and threonine metabolism, and glutathione metabolism of the intestinal bacterial community in NAFLD mice.

Conclusions: ETB was effective in ameliorating the NAFLD, possibly by remodelling the gut microbiota composition and modulating the faecal metabolism metabolites of the host, highlighting the potential of TB as a resource for the development of anti-NAFLD drugs.

Keywords: Gut microbiota; Metabolomics; Nonalcoholic fatty liver disease; Terminalia bellirica; Tibetan medicine.

MeSH terms

Animals
Diet, High-Fat
Ethanol / pharmacology
Gastrointestinal Microbiome*
Liver
Mice
Mice, Inbred C57BL
Non-alcoholic Fatty Liver Disease* / metabolism
RNA, Ribosomal, 16S / genetics
RNA, Ribosomal, 16S / metabolism
Terminalia*

Substances

Ethanol
RNA, Ribosomal, 16S