Hedan tablet ameliorated non-alcoholic steatohepatitis by moderating NF-κB and lipid metabolism-related pathways via regulating hepatic metabolites.

Non-alcoholic steatohepatitis (NASH) is a severe form of fatty liver disease. If not treated, it can lead to liver damage, cirrhosis and even liver cancer. However, advances in treatment have remained relatively slow, and there is thus an urgent need to develop appropriate treatments. Hedan tablet (HDP) is used to treat metabolic syndrome. However, scientific understanding of the therapeutic effect of HDP on NASH remains limited. We used HDP to treat a methionine/choline-deficient diet-induced model of NASH in rats to elucidate the therapeutic effects of HDP on liver injury. In addition, we used untargeted metabolomics to investigate the effects of HDP on metabolites in liver of NASH rats, and further validated its effects on inflammation and lipid metabolism following screening for potential target pathways. HDP had considerable therapeutic, anti-oxidant, and anti-inflammatory effects on NASH. HDP could also alter the hepatic metabolites changed by NASH. Moreover, HDP considerable moderated NF-κB and lipid metabolism-related pathways. The present study found that HDP had remarkable therapeutic effects in NASH rats. The therapeutic efficacy of HDP in NASH mainly associated with regulation of NF-κB and lipid metabolism-related pathways via arachidonic acid metabolism, glycine-serine-threonine metabolism, as well as steroid hormone biosynthesis.

Er-Chen Decoction Alleviates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease in Rats through Remodeling Gut Microbiota and Regulating the Serum Metabolism.

Many studies have found that the dysfunction in gut microbiota and the metabolic dysfunction can promote nonalcoholic fatty liver disease (NAFLD) development. Er-Chen decoction (EC) can be used in the treatment of NAFLD. However, the mechanism of this hepatoprotection is still unknown. In this study, we constructed a rat model with NAFLD fed with high-fat chow and administered EC treatment. The therapeutic effects of EC on NAFLD were evaluated by measuring transaminases, blood lipid levels, and pathological changes in the liver. In addition, we measured the effects of EC on liver inflammatory response and oxidative stress. The changes in gut microbiota after EC treatment were studied using 16S rRNA sequencing. Serum untargeted metabolomics analysis was also used to study the metabolic regulatory mechanisms of EC on NAFLD. The results showed that EC decreased the serum transaminases and lipid levels and improved the pathological changes in NAFLD rats. Furthermore, EC enhanced the activities of SOD and GSH-Px and decreased MDA level in the liver. EC treatment also decreased the gene and protein levels of IL-6, IL-1ß, and TNF-α in the liver and serum. The 16S rRNA sequencing and untargeted metabolomics indicated that EC treatment affected the gut microbiota and regulated serum metabolism. Correlation analysis showed that the effects of EC on taurine and hypotaurine metabolism, cysteine and methionine metabolism, and vitamin B6 metabolism pathways were associated with affecting in the abundance of Lactobacillus, Dubosiella, Lachnospiraceae, Desulfovibri, Romboutsia, Akkermansia, Intestinimonas, and Candidatus_saccharimonas in the gut. In conclusion, our study confirmed the protective effect of EC on NAFLD. EC could treat NAFLD by inhibiting oxidative stress, reducing inflammatory responses, and improving the dysbiosis of gut microbiota and the modulation of the taurine and hypotaurine metabolism, cysteine and methionine metabolism, and vitamin B6 metabolism pathways in serum.

Effect of Jiangan-Jiangzhi Pill on Gut Microbiota and Chronic Inflammatory Response in Rats with Non-Alcoholic Fatty Liver.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease with high rates of occurrence. Research has found that NAFLD patients experience varying degrees of intestinal flora imbalance. There is evidence that traditional Chinese medicine (TCM) positively regulates imbalances in the gut microbiota caused by liver diseases. Jiangan-Jiangzhi pill (JGJZ) is a common Chinese remedy that can treat NAFLD clinically. This article investigates how JGJZ affects NAFLD and assesses related changes in the intestinal flora. We established a NAFLD rat model by feeding them a high-fat diet (HFD) and gave different interventions. After twelve weeks, the results revealed that JGJZ decreased the total cholesterol, triglyceride, alanine aminotransferase, and aspartate aminotransferase in the serum of NAFLD rats. Histopathological staining demonstrated that JGJZ relieved cellular fat accumulation in the liver. Inflammatory cytokine levels (IL-6, IL-1ß, and TNF-α) were down-regulated. Analysis of 16S rRNA demonstrated that JGJZ changed the community compositional structure of gut microbiota, characterized by a decrease in the Firmicutes-to-Bacteroidetes ratio, and increased gut microbiota diversity and the abundance of dominant groups. Accordingly, our study illustrated that JGJZ exerted a better effect in treating HFD-induced NAFLD, which may be closely related to ameliorating gut microbiota dysbiosis.

Traditional Chinese Medicine Ganshuang Granules Attenuate CCl4 -Induced Hepatic Fibrosis by Modulating Gut Microbiota.

Gut dysbiosis contributes to hepatic fibrosis. Emerging evidence revealed the major role of traditional Chinese medicine (TCM) in gut microbiota homeostasis. Here, we aimed to investigate the anti-fibrotic activity and underlying mechanism of ganshuang granules (GS), particularly regarding gut microbiota homeostasis. CCl4 -induced hepatic fibrosis models were allocated into 4 groups receiving normal saline (model), 1.0, 2.0, or 4.0 g/kg GS for 5 weeks. As result, GS treatment alleviated liver injury in CCl4 -induced hepatic fibrosis, presenting as decreases of the liver index, alanine aminotransferase, and aspartate transaminase. Histological staining and expression revealed that the enhanced oxidative stress, inflammatory and hepatic fibrosis in CCl4 -induced models were attenuated by GS. Immunohistochemical staining showed that tight junction-associated proteins in intestinal mucosa were up-regulated by GS. 16S rRNA sequencing showed that GS rebalanced the gut dysbiosis manifested as improving alpha and beta diversity of gut microbiota, reducing the ratio of Firmicutes to Bacteroidetes, and regulating the relative abundance of various bacteria. In summary, GS decreased the intestinal permeability and rebalanced the gut microbiota to reduce the oxidative stress and inflammation, eventually attenuating CCl4 -induced hepatic fibrosis.