Abstract
Objective This study aimed to decipher the bioactive compounds and potential mechanism of traditional Chinese medicine (TCM) formula Fuzi Lizhong Decoction (FLD) for nonalcoholic fatty liver disease (NAFLD) treatment via an integrative network pharmacology approach. Methods The candidate compounds of FLD and its relative targets were obtained from the TCMSP and PharmMapper web server, and the intersection genes for NAFLD were discerned using OMIM, GeneCards, and DisGeNET. Then, the PPI and component-target-pathway networks were constructed. Moreover, GO enrichment and KEGG pathway analysis were performed to investigate the potential signaling pathways associated with FLD's effect on NAFLD. Eventually, molecular docking simulation was carried out to validate the binding affinity between potential core components and key targets. Results A total of 143 candidate active compounds and 129 relative drug targets were obtained, in which 61 targets were overlapped with NAFLD. The PPI network analysis identified ALB, MAPK1, CASP3, MARK8, and AR as key targets, mainly focusing on cellular response to organic cyclic compound, steroid metabolic process, and response to steroid hormone in the biological processes. The KEGG pathway analysis demonstrated that 16 signaling pathways were closely correlated with FLD's effect on NALFD with cancer pathways, Th17 cell differentiation, and IL-17 signaling pathways as the most significant ones. In addition, the molecular docking analysis revealed that the core active compounds of FLD, such as 3′-methoxyglabridin, chrysanthemaxanthin, and Gancaonin H, had a high binding activity with such key targets as ALB, MAPK1, and CASP3. Conclusions This study suggested that FLD exerted its effect on NAFLD via modulating multitargets with multicompounds through multipathways. It also demonstrated that the network pharmacology-based approach might provide insights for understanding the interrelationship between complex diseases and interventions of the TCM formula.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is a metabolic disorder with excessive hepatic fat deposition in the absence of significant alcoholic consumption, application of susceptible medication, or other preexisting liver conditions [1]
After removing the duplicate targets, the protein targets related to NAFLD were imported to the Uniprot data platform. en, the acquired genes were input to draw Venn diagrams using Venny2.1(https://bioinfogp.cnb.csic.es/tools/venny/), and the intersection genes were obtained as candidate genes
Some compounds were overlapped across different herbs, including sitosterol (ID: MOL000359) in FZ, GJ, and GC, beta-sitosterol (ID: MOL000358) in GJ and RS, and kaempferol (ID: MOL000422) in RS and GC
Summary
Nonalcoholic fatty liver disease (NAFLD) is a metabolic disorder with excessive hepatic fat deposition in the absence of significant alcoholic consumption, application of susceptible medication, or other preexisting liver conditions [1]. As the most common chronic liver disease, NAFLD encompasses a broad spectrum of liver damage and has been considered a cause of end-stage liver disease. It is assumed to be associated with increased rates of hepatocellular carcinoma and death and is projected to become the leading cause of cirrhosis that requires liver transplantation. Metabolic complications, and genetic variants, including PNPLA3 and TM6SF2, may play a role [4], the pathogenesis of NAFLD remains incompletely decoded, and no pharmacological interventions have been officially approved. The treatment options available for NAFLD patients are still limited and mainly based on nutrition and exercise [5]. The treatment options available for NAFLD patients are still limited and mainly based on nutrition and exercise [5]. erefore, there is an urgent need for the research and development of novel medical interventions
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