Abstract
Objective To explore the potential active components and corresponding target herb pairs of Radix Ginseng (Renshen) and Radix Bupleuri (Chaihu) in the treatment of nonalcoholic fatty liver disease (NAFLD) through network pharmacology and in vitro experiments. Methods The active components and potential targets of the herb pair of Renshen and Chaihu were screened through a network database system, and Venn analysis was performed with the obtained NAFLD targets. The intersecting targets were analysed for gene ontology (GO) functions and Kyoto Encyclopedia of Genes and Genome (KEGG) pathways, and a protein-protein interaction (PPI) network was generated. Cytoscape software was used to construct active component-target networks of the Renshen and Chaihu herb pair. Free fatty acids were added to the HepG2 cell line to create high-fat models that were treated with different concentrations of stigmasterol. The effect of stigmasterol on the lipid metabolism in HepG2 cells and PPARγ-knockdown cells was determined by oil red O staining, Nile red staining, and TG level. PPARγ and UCP-1 mRNA, and protein expression levels were detected by qRT-PCR and Western blot analyses, respectively. Results Twenty active components obtained from the Renshen and Chaihu herb pair were identified. The herb pair active component-target network showed that both Renshen and Chaihu contained stigmasterol and kaempferol as active components. The PPI network comprised 63 protein nodes. GO enrichment analysis and KEGG pathway enrichment analysis showed that the targets were mainly involved in lipid metabolism. Eight core targets were identified: AKT1, PPARG, MAPK3, TNF, TP53, SIRT1, STAT3, and PPARA. In vitro experiments demonstrated that stigmasterol reduced lipid accumulation and TG levels in HepG2 cells, and the mechanism may have been related to the activation of the PPARγ-UCP-1 signalling pathway. Conclusion This study preliminarily illustrated the potential components and corresponding core targets of the Renshen and Chaihu herb pair in treating NAFLD. The effect of stigmasterol on the PPARγ-UCP-1 signalling pathway in enhancing lipid metabolism may represent one of the mechanisms of the Renshen and Chaihu herb pair in the treatment of NAFLD. The results provide new evidence and research insights to reveal the roles of Renshen and Chaihu in the management of NAFLD.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is caused by metabolic stress-induced liver injury closely related to insulin resistance and genetic susceptibility
According to the defined value of bioavailability, herb-like properties, and deduplication processing, 17 active components contained in Chaihu (Table 1) and 22 active components contained in Renshen (Table 2) were obtained from the TCMSP database
Renshen and Chaihu herb pair active component-potential target regulatory networks were constructed using Cytoscape 3.7.2 software (Figure 1(a)). e 592 targets of the Renshen and Chaihu herb pair were crossed with the 333 NAFLD-related targets obtained from the DisGeNET database
Summary
Nonalcoholic fatty liver disease (NAFLD) is caused by metabolic stress-induced liver injury closely related to insulin resistance and genetic susceptibility. One of the most common hepatic diseases worldwide, NAFLD is a spectrum disease that includes nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH), and liver cirrhosis [1]. A recent systematic review has indicated that the prevalence of NAFLD is as high as 29.2% in China [2]. E pathophysiology of NAFLD is not yet clear; lipotoxic response is clearly a central mechanism of NAFLD development and progression [3] Based on this understanding, various chemical agents have been developed and are under investigation to explore their potential benefits [4]. In China, many patients seek medical consultations from practitioners of traditional Chinese medicine (TCM) and consume Chinese herbal medicines (CHMs)
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