ORIGINAL RESEARCH article
Front. Med.
Sec. Hepatobiliary Diseases
Quercetin alleviates rifampicin-induced hepatocyte injury by modulating the Hippo-YAP signaling pathway
Provisionally accepted
- Nanjing University of Chinese Medicine, Nanjing, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Objective: To investigate the protective effects of Quercetin, an antioxidant and anti-apoptotic flavonoid, against rifampicin (RFP)-induced hepatocyte injury via the Hippo-YAP signaling pathway. Methods: A rifampicin-induced hepatocyte injury model was established using HepaRG cells. HepaRG cells were divided into Control, RFP Model, Quercetin (15 μM), and Verteporfin (YAP inhibitor) groups. Cell viability was assessed by the CCK-8 assay, apoptosis by Annexin V/PI staining, and mitochondrial membrane potential (MMP) by TMRE staining. YAP localization was evaluated by immunofluorescence, and the expression of Hippo–YAP and apoptosis-related genes was analyzed by Western blot and qRT-PCR. Results: Quercetin significantly improved cell viability, reduced apoptosis, and restored MMP in RFP-injured HepaRG cells. RFP activated the Hippo pathway by upregulating MST1 and LATS1, increasing YAP phosphorylation, and promoting apoptosis-related protein expression (Caspase-3, BAX), while downregulating anti-apoptotic BCL-2. Quercetin reversed these effects by inhibiting MST1/LATS1 activation, reducing YAP phosphorylation, and promoting its nuclear translocation. The protective effects were partially attenuated by Verteporfin, indicating Hippo–YAP pathway involvement. Conclusion: Quercetin alleviates RFP-induced hepatocyte injury by suppressing Hippo pathway kinases MST1 and LATS1, reducing YAP phosphorylation, and enhancing YAP nuclear translocation, thereby improving MMP and inhibiting apoptosis.
Keywords: Quercetin, Hippo-yap, Drug-Induced Liver Injury, Apoptosis, rifampicin
Received: 18 Sep 2025; Accepted: 30 Oct 2025.
Copyright: © 2025 Liu, Li and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Weimin Lu, lwm128101@163.com
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.