Abstract

Erzhi pill (EZP), a classical traditional Chinese medicine prescription, exerts a potent hepatoprotective effect against metabolic dysfunction-associated fatty liver disease (MAFLD), previously known as nonalcoholic fatty liver disease (NAFLD). However, the mechanism and bioactive compounds underlying the hepatoprotective effect of EZP have not been fully elucidated. In this study, a systematic analytical platform was built to explore the mechanism and bioactive compounds of EZP against MAFLD. This was carried out through target prediction, protein-protein interaction (PPI) network construction, gene ontology, KEGG pathway enrichment, and molecular docking. According to the topological parameters of the PPI network, compound-target-pathway network, 9 targets, and 11 bioactive compounds were identified as core targets and bioactive compounds for molecular docking. The results showed that EZP exerts anti-MAFLD effects through a multicomponent, multitarget, multipathway manner, and luteolin and linarin may be the bioactive compounds of EZP. This study provides further research insights and helps explore the hepatoprotective mechanism of EZP.

Highlights

  • Metabolic dysfunction-associated fatty liver disease (MAFLD), previously known as nonalcoholic fatty liver disease (NAFLD) [1, 2], is defined as the presence of liver cells with steatosis exceeding 5% and the lack of secondary causes of liver fat accumulation, such as drinking of alcohol [3]

  • The date for Erzhi pill (EZP) compounds were mainly obtained from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP, http://lsp.nwu.edu.cn/tcmsp.php, Version 2.3), a pharmacology platform that provides information on drugs, targets, and diseases, by retrieving Fructus Ligustri Lucidi and Ecliptae Herba

  • The results showed that MOL000006 and MOL001790 have the lowest binding energy with 3 of the 9 core targets; MOL005169, MOL005188, and MOL005209 have the lowest binding energy with 1 of the 9 core targets, which means that these five compounds may have more important functions in the regulatory network of EZP against MAFLD

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Summary

Introduction

Metabolic dysfunction-associated fatty liver disease (MAFLD), previously known as nonalcoholic fatty liver disease (NAFLD) [1, 2], is defined as the presence of liver cells with steatosis exceeding 5% and the lack of secondary causes of liver fat accumulation, such as drinking of alcohol [3]. The MAFLD has developed into a global health concern over the past decades [4]. Significant weight loss and change of dietary habits will have a salutary effect on MAFLD; new treatment strategies are urgently needed [7]. The reason is that with the changing dietary habits and lifestyle, MAFLD is one of the most important causes of liver disease worldwide. MAFLD may eventually become the primary cause of end-stage liver disease [4]. There is an urgent need for safe and effective drugs against MAFLD

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