Mechanisms of Picrasma quassioides against hepatocellular carcinoma elucidated by network pharmacology and experimental validation.

Abstract

Objective: The medicinal plant Picrasma quassioides (P. quassioides) Benn exerts an inhibitory effect on the growth of hepatocellular carcinoma (HCC) cells via an unknown mechanism. This study explored the targets and signaling pathways underlying the mechanism of P. quassioides against HCC.

Methods: Targets of P. quassioides active compounds were identified using the HERB database, and the HCC targets were found with the GeneCards database. The optimal serum concentration and intervention time were determined using the CCK-8 assay. Apoptosis, cell cycle, invasion, cloning, and wound-healing abilities were assessed using flow cytometry. Core protein targets and signaling pathway-related metabolic enzymes were evaluated with Western blotting. The anti-HCC effect of P. quassioides medicated serum was verified using arachidonic acid (AA)-related enzyme agonists.

Results: Network pharmacology identified 19 effective compounds of P. quassioides and 105 HCC-associated targets. It also revealed the AA pathway was the central pathway of P. quassioides against HCC, with AURKA, AURKB, KIF11, and TOP2A identified as core targets that inhibit excessive HCC cell proliferation and promote apoptosis. Flow cytometry findings supported that P. quassioides medicated serum significantly inhibited HCC cell proliferation and promoted apoptosis. By contrast, enzyme agonists related to the AA pathway markedly counteracted the anti-HCC effect of P. quassioides, promoting HCC growth.

Conclusion: P. quassioides medicated serum exerts a prominent anti-HCC effect in vitro. The AA pathway constitutes the mechanism by which P. quassioides medicated serum inhibits excessive proliferation and promotes apoptosis of HCC cells.