Yinzhihuang oral liquid protects against non-alcoholic steatohepatitis via modulation of the gut-liver axis in mice

Abstract

Background: Yinzhihuang (YZH) oral liquid is a traditional Chinese medicine compound that has emerged as a promising therapeutic agent for non-alcoholic fatty liver disease (NAFLD). Here, we aimed to investigate the therapeutic effects of YZH on non-alcoholic steatohepatitis (NASH) and elucidate its underlying molecular mechanisms.Methods: Mice fed on a high-fat diet plus fructose/glucose drinking water (HFGD) were treated with YZH (30 mL/kg/d). The effects of YZH on mice with NASH were assessed through serological analysis and histological examination. Microbiota analysis based on 16S ribosomal ribonucleic acid (16S rRNA) and intestinal mucosal barrier function, serum inflammatory factors, hepatic macrophage infiltration, as well as hepatic toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor kappa B (NFκB) pathway were carried out to explore the mechanism of YZH for treatment of NASH.Results: Results of the current study found that YZH effectively reduced body weight gain and adiposity and alleviated hepatocyte steatosis, hepatocyte ballooning, liver tissue lobular inflammation, as well as fibrosis. It also reduced the accumulation of triglycerides, cholesterol, and free fatty acids in the liver of the treated mice and normalized serum aspartate transaminase, alanine transaminase, and glucose levels as well as lipid metabolism. Meanwhile, YZH treatment significantly decreased the abundance of harmful bacteria, such as Mucispirillum, Helicobacter, and Desulfovibrionaceae. Mechanistically, the present study found that YZH upregulated the expression of tight junction proteins, decreased serum lipopolysaccharide, interleukin 6, and tumor necrosis factor α levels, and increased interleukin 10 levels in serum. In the liver, YZH alleviated macrophage infiltration, especially that of pro-inflammatory macrophages. Moreover, it was found that YZH inhibited the canonical TLR4, MyD88, NFκB signaling pathway. Conclusions:In conclusion, YZH may be a new agent for the prevention of NASH. Further, YZH alleviates gut microbiota dysbiosis, restores the intestinal mucosal barrier, and inhibits the canonical TLR4, MyD88, NFκB signaling pathway.

Chinese medicine in the treatment of non-alcoholic fatty liver disease based on network pharmacology: a review

“… Zeng, et al (2020) also confirmed that Yinzhihuang liquid (YZHL) can effectively accelerate lipid β oxidation, relieve liver necrotic inflammation, inhibit lipogenesis and relieve oxidative stress, and finally achieve the effect of treating nonalcoholic steatohepatitis in rats. YZHL is also able to regulate the gut-liver axis to prevent the occurrence of NASH in mice, and play a role in reducing body weight, preventing obesity and alleviating hepatocyte steatosis ( Li, et al, 2022 ). The above proprietary Chinese medicines have different degrees of efficacy in the treatment of NAFLD, and are widely used in clinical practice ( Supplementary Table S1 ).…”

Tactics with Prebiotics for the Treatment of Metabolic Dysfunction-Associated Fatty Liver Disease via the Improvement of Mitophagy

“…The gut dysbiosis could accelerate the development of MAFLD due to abnormal levels of gut microbial metabolites and/or their effects on gut epithelial permeability [ 109 , 110 ]. Therefore, it has been shown that the gut microbiota might play an imperative role in the progression of MAFLD, and gut microbiota dysbiosis may be a significant factor in MAFLD pathogenesis [ 111 , 112 ].…”

Mechanisms and Therapeutic Strategies for MAFLD Targeting TLR4 Signaling Pathways

“…Certain traditional Chinese medicines, such as Chinese herbs, Chinese herbal formulations, and Chinese patent medicines, have shown effectiveness in reducing hepatic steatosis and inflammation in MAFLD (shown in Table 1) [73‒100].…”