Unveiling the mechanism of Baoyuan Jiedu Decoction in cancer cachexia-induced lipolysis through network pharmacology and bioinformatics.

BACKGROUND AND AIM: Baoyuan Jiedu Decoction (BJD) has demonstrated therapeutic potential against cancer-related cachexia (CC); however, its precise pharmacological mechanisms remain unclear. This study aims to elucidate the effects of BJD on CC-induced lipolysis and explore its underlying mechanisms. EXPERIMENTAL PROCEDURE: The chemical composition of BJD was characterized using UPLC-Q-TOF/MS and potential targets related to CC and lipolysis were identified through network pharmacology, bioinformatics analysis, and random forest analysis. The efficiencies and mechanisms of BJD were further confirmed in LLC tumor-bearing mice. RESULTS AND CONCLUSION: We identified 120 active components in BJD and, by means of network pharmacology, bioinformatics and random forest analysis, identified PIK3R1 and HSP90AA1 as the key therapeutic targets. In LLC tumor-bearing mice, BJD significantly alleviated the symptoms of CC, reducing the serum levels of free fatty acids and glycerol. Furthermore, BJD downregulated the expression of HSP90AA1 and upregulated that of PIK3R1 in tumors. In iWAT and eWAT, BJD also decreased the expression of ATGL and p-HSL, indicating the inhibition of lipolysis induced by CC. These findings suggest that BJD mitigates lipolysis in CC through modulating PIK3R1 and HSP90AA1, providing valuable insights into its therapeutic mechanism.