Pharmacodynamic Evaluation of the Gexia Zhuyu Decoction in the Treatment of NAFLD and the Molecular Mechanism Underlying the TRPM4 Pathway Regulation.

Yao-Wei Zhao,Rui Wang,Xin-Dan Liang,Jing Yang,Tong Wang,Jie Niu,Yang Ren,Isac Medeiros

doi:10.1155/2021/3364579

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome of abnormal lipid deposition in the liver mediated by nonalcohol intake. The Gexia Zhuyu decoction, a classic traditional Chinese medicine compound, is widely used in the clinical treatment of NAFLD. However, its specific efficacy and underlying mechanisms have not been elucidated yet. This study aimed to quantitatively evaluate the efficacy of the Gexia Zhuyu decoction using pharmacodynamics and to explore its molecular mechanisms in conjunction with proteomics. High-fat diets and methionine choline-deficient diets were used to induce various NAFLD progression stages in mouse models. The effects of oral Gexia Zhuyu decoction administration on NAFLD were evaluated by measuring the serum and liver indicators of the treated mice before and after drug intervention and by comparing the changes in liver tissue. Liver TRPM4 mRNA and protein levels were measured using reverse transcription-polymerase chain reaction and Western blotting, respectively. Experimental data showed that serum ALT, AST, and liver triglyceride (TG) levels in each disease stage group of drug intervention mice decreased, and high-density lipoprotein (HDL) and superoxide dismutase (SOD) levels increased. Liver TG levels decreased after drug intervention in the liver fibrosis mice, but serum TG levels increased. Furthermore, cellular fatty changes, inflammatory changes, and fibrous tissue proliferation were all relieved. The TRPM4 protein and mRNA levels in the liver tissue were decreased, and the microRNA (miRNA)-24 expression was increased. The Gexia Zhuyu decoction has a clear therapeutic effect at each stage of NAFLD. It likely acts by altering miRNA-24 expression and regulating the target TRPM4 protein pathway to achieve NAFLD treatment.

Highlights

Nonalcoholic fatty liver disease (NAFLD), commonly associated with chronic liver damage, is usually accompanied by metabolic complications, such as elevated blood lipid and blood glucose levels, uncontrolled blood pressure, and vascular dysfunction
Water was added ten times the compound dose, and the mixture was fully soaked for 60 min and decocted twice for 2 h each. e Gexia Zhuyu decoction was prepared as a mixture of these two decocted solutions. rough the HPLC analysis of Gexia Zhuyu decoction, the determination results showed that the total amount of hydroxyl safflower yellow pigment A in Gexia Zhuyu decoction was greater than 0.25 mg/mL and the total amount of ferulic acid was greater than 0.22 mg/mL, in line with the standard, can be used for intragastric administration, into the pharmacodynamics study
Ordinary feed was purchased from the Experimental Animal Center of Heilongjiang University of Traditional Chinese Medicine (Harbin, China); 45% kcal high-fat diet-induced obesity (DIO) diets were purchased from Research Diets Inc. (New Brunswick, NJ, USA); and methionine choline-deficient (MCD) diets were purchased from Moldiets (Beijing, China) [25, 26]. e study was performed in accordance with the ARRIVE guidelines

Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD), commonly associated with chronic liver damage, is usually accompanied by metabolic complications, such as elevated blood lipid and blood glucose levels, uncontrolled blood pressure, and vascular dysfunction. Epidemiological surveys [3, 4] have shown that the prevalence of NAFLD in China has risen sharply in the past ten years, by as much as 26–45%, and is the most common chronic liver disease in the country. Erefore, symptomatic treatment is often employed clinically, including lipid-lowering and glucose and lipid metabolism improvements. Most lipid-lowering drugs degrade blood lipid levels and promote lipid entry into the liver for metabolism and excretion, which can lead to liver damage and liver fat deposition [6]. Most lipid-lowering drugs degrade blood lipid levels and promote lipid entry into the liver for metabolism and excretion, which can lead to liver damage and liver fat deposition [6]. erefore, it has Evidence-Based Complementary and Alternative Medicine become an urgent task to find a drug that has clear therapeutic effects, is safe, and has minimal side effects

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