Hibiscus cannabinus L. leaves (HCLLs) are considered a favorable source of natural antiobesity substances. However, actual bioactive compound(s) in it and their mechanism(s) against
obesity have not been confirmed. Hence, network pharmacology was conducted to identify its key compounds and mechanism(s) against
obesity. Compounds in HCLLs were identified through GC-MS analysis and screened by Lipinski's rule. Genes related to the selected compounds and
obesity were obtained from public databases, and overlapping genes between HCLL compound-related genes and
obesity target genes were selected using a Venn diagram. The networking between selected compounds and overlapping genes was then constructed, visualized, and analyzed by RStudio. Finally, the binding affinity between compounds and genes was evaluated via molecular docking (MD). A total of 30 compounds in HCLLs were detected via GC-MS, and Lipinski's rule accepted all compounds. The compound-related genes (570 genes) and
obesity targeted genes (3028 genes) were identified, and between them, 64 overlapping genes were selected. Gene Set Enrichment Analysis (GSEA) displayed that the mechanisms of HCLLs against
obesity were associated with 13 signaling pathways on 22 compounds in HCLLs. Superficially, AKT1,
vitamin E, and RAS signaling pathways were noted as a hub gene, an uppermost bioactive compound, and a hub signaling pathway, respectively. However, the binding affinity of
ligands and
proteins on the RAS signaling pathway was very low; instead, the
PPAR signalling pathway was evaluated with potent efficacy against
obesity through MD. On the
PPAR signaling pathway, α-amyrin was found as the most significant compound for the amelioration of
obesity. α-Amyrin manifested the strongest binding affinity on six target
proteins associated with the
PPAR signaling pathway. Our study suggests that an auxiliary (
PPAR) signaling pathway of HCLLs might intervene efficiently against
obesity over the hub (RAS) signaling pathway.