Quercetin 7-rhamnoside from Sorbaria sorbifolia exerts anti-hepatocellular carcinoma effect via DHRS13/apoptotic pathway

•For the first time, it has been discovered that the component Quercetin 7-rhamnoside (Q7R) from Sorbaria sorbifolia exhibits notable anti-hepatocellular carcinoma efficacy.•The abnormal expression of DHRS13 protein was found in liver cancer tissues, and Q7R can lower liver cancer cell proliferation by inhibiting DHRS13 protein expression.•Our previous research revealed that SS can inhibit liver cancer by activating the apoptotic pathway (Xu et al., 2024). In this study, we have found that Q7R can exhibit anti-hepatocellular carcinoma effects by regulating the apoptotic pathway through DHRS13. Previous research demonstrated the effects of Sorbaria sorbifolia (SS) in combating hepatocellular carcinoma (HCC). Despite SS's proven efficacy in treating HCC, the precise bioactive constituents contributing to its therapeutic benefits, along with the mechanisms behind them, warrant further exploration. The objective of our study was to illuminate the possible elements, targets, and modulatory pathways employed by specific bioactive components in SS for HCC treatment. Using UPLC-Q-TOF-MS to analyze and quantify the bioactive constituents in the SS sample. By literature review, we gathered potential chemical constituents of SS. We used network pharmacology approaches to identify HCC-related targets of SS components, with an emphasis on core targets. To examine the core targets' importance in HCC biological processes, bioinformatics methods were utilized. Finally, molecular docking, MD simulations, and CESTA were employed to screen SS active ingredients capable of stably binding with core targets. To verify the anti-HCC effectiveness of these active components, we conducted several cellular experiments, including CCK8, wound healing, transwell, cell cycle, and apoptosis assays, as well as animal experiments like zebrafish HepG2 cell xenotransplantation, apoptosis assays, and HE staining. We also used lentivirus transfection to modulate core protein expression in HepG2 cells, creating cell models. Further cellular tests were performed to evaluate the ability of SS active ingredients to exert anti-HCC effects by interacting with the core protein to induce apoptosis. Finally, Western Blot and ELISA experiments were carried out to track changes in core protein and apoptosis-related pathway proteins after SS active ingredient treatment Our study identified 50 components in SS and 119 HCC-related target genes, with DHRS13 emerging as a core target. Further bioinformatics a