Protective Effects and Mechanisms of Yinchen Linggui Zhugan Decoction in HFD-Induced Nonalcoholic Fatty Liver Disease Rats Based on Network Pharmacology and Experimental Verification

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease, characterized by excessive accumulation of hepatocyte fat. However, there is no exact and effective pharmacotherapy for NAFLD. Yinchen linggui zhugan decoction (YLZD) has been widely used to treat NAFLD. Nevertheless, its pharmacological and molecular mechanisms have not been clearly elucidated. This study was carried out to investigate the active components of YLZD and explore its potential mechanisms for treating NAFLD by network pharmacology and experimental verification. The results showed that a total of 120 active components of YLZD and 365 targets were retrieved through databases, and the main active ingredients of YLZD consisted of chlorogenic acid, emodin, aloe-emodin, rhein, and geniposide. KEGG enrichment analysis revealed fundamental roles of TNF, PI3K/AKT, HIF-1α, and insulin resistance signaling pathways in the treatment of NAFLD by YLZD. Moreover, our experimental verification results showed that YLZD improved the liver pathological and cholesterol level, and reduced the expressions of TNF-α, IL-1β, IL-6, NF-κB, CCL2, and CXCL10 in NAFLD rats, which all belonged to TNF signaling pathway. The molecular docking confirmed the correlation between the four core components (chlorogenic acid, emodin, rhein, and geniposide) and key factors (TNF-α, IL-6, and NF-κB) in TNF signaling pathway. In conclusion, the present study systematically clarified the protective mechanisms of YLZD against NAFLD through targeting the TNF signaling pathway, and provided new ideas for the drug research of this disease.

Yinchen Linggui Zhugan decoction ameliorates high fat diet-induced nonalcoholic fatty liver disease by modulation of SIRT1/Nrf2 signaling pathway and gut microbiota

“…In addition, YLZD can improve liver function in NAFLD rats, significantly reducing AST and ALT levels. Our previous study ( Jiang et al, 2022 ) found that the improvement was more pronounced with increasing the dose of YLZD administration, and no obvious hepatotoxic effects were observed. It follows that YLZD has an effective therapeutic effect on NAFLD and its potential intervention mechanism is worthy of further investigation.…”

“…The formulation granule process is made by Beijing Tcmages Pharmaceutical Co., Ltd. (Beijing, China) using Chinese herbal medicine as raw materials through the steps of extraction, separation, concentration, drying, granulation and packaging. The main components of YLZD formula granules were identified as chlorogenic acid, geniposide, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, aloe-emodin, rhein, glycyrrhizic acid, and emodin by High Performance Liquid Chromatography (HPLC) with the specific corresponding contents of 2.8521, 11.8532, 0.6459, 0.3511, 0.8627, 0.0971, 0.1098, 2.9140, and 0.0088 (mg/g), respectively ( Jiang et al, 2022 ).…”

“…The YLZD granules were dissolved in water (0.192 g/ml) at 80°C, cooled to room temperature and then gavaged. The dose of YLZD gavage was 10 ml/kg/day, which was the optimal intervention dose screened in our previous study ( Jiang et al, 2022 ). Control and HFD group were gavaged with sterile distilled water (10 ml/kg).…”

Aqueous extract of Artemisia capillaris improves non-alcoholic fatty liver and obesity in mice induced by high-fat diet

“…WAC decreased TG content and reduced lipid deposition in liver and HepG2 cells. Although there are no reports of WAC affecting Frontiers in Pharmacology frontiersin.org 13 NAFLD through the PI3K/AKT signaling pathway, it has been shown that chlorogenic acid prevents HFD-induced hepatic steatosis and may achieve this effect by modulating intestinal flora and increasing GLP-1 secretion (Jiang et al, 2022).…”

Shenling Baizhu San ameliorates non-alcoholic fatty liver disease in mice by modulating gut microbiota and metabolites

“…However, there are no approved agents available for use ( Patel et al, 2020 ; Ratziu et al, 2020 ; Huang et al, 2021 ). There is a growing body of evidence indicating that traditional Chinese medicine (TCM) can prevent and treat early-stage NAFLD ( Dang et al, 2020 ; Jiang et al, 2022 ); TCM may therefore complement lifestyle approaches to preventing and treating NAFLD.…”