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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Gastrointestinal and Hepatic Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1539744
This article is part of the Research Topic Advanced Therapeutic Strategies in Digestive and Circulatory Health: Nanomedicine and Beyond View all 4 articles

Rutaecarpine Alleviates Hepatic Ischemia-reperfusion Injury in Liver Transplantation by Inhibiting Inflammatory Response and Oxidative Stress

Provisionally accepted
Yan Liu Yan Liu 1,2Feng Qi Feng Qi 1Lun-Jian Xiang Lun-Jian Xiang 2Zhujun Yi Zhujun Yi 2Shengwei Li Shengwei Li 1*
  • 1 Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
  • 2 Chongqing Three Gorges University, Wanzhou, Chongqing Municipality, China

The final, formatted version of the article will be published soon.

    Background: Donation after circulatory death (DCD) livers are limited by mandatory warm ischemia and are more susceptible to ischemia-reperfusion injury (IRI). Inflammation and oxidative stress play key roles in the development of hepatic IRI, and Rutaecarpine (Rut) has anti-inflammatory and anti-oxidative stress effects. The aim of this study was to investigate whether Rut can alleviate hepatic IRI in liver transplantation (LT) and to explore the underlying mechanisms.Methods: Rat DCD LT and oxygen-glucose deprivation/reoxygenation (OGD/R) cell models were established to clarify the effect of Rut on hepatic IRI. The key molecules involved in the hepatoprotective effects of Rut were identified through joint analysis of data from LT patients and drug targets. The target was further validated by in silico, in vivo and in vitro experiments.Results: Rut significantly alleviated liver dysfunction, pathological injury, and apoptosis and improved the survival rate of the rats subjected to LT. In addition, Rut significantly inhibited inflammatory response and oxidative stress. Rut also had similar effects on OGD/R-induced hepatocyte injury. Mechanistically, bioinformatics analysis and in vivo and in vitro experiments revealed that PDE4B may be a key target by which Rut exerts its protective effect, and molecular docking and cellular thermal shift assay confirmed this result. The function of PDE4B was studied via gene intervention technology, and the results showed that PDE4B can aggravate hepatic IRI. Furthermore, PDE4B overexpression abrogated the protective effect of Rut on the liver in LT.Conclusions: Rut alleviates hepatic IRI by targeting PDE4B to inhibit inflammation and oxidative stress. These findings highlight the potential of Rut as a drug candidate for the treatment of patients undergoing LT.

    Keywords: Donation after circulatory death, Liver Transplantation, Rutaecarpine, Oxidative Stress, Inflammatory Response

    Received: 04 Dec 2024; Accepted: 20 Jan 2025.

    Copyright: © 2025 Liu, Qi, Xiang, Yi and Li. 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: Shengwei Li, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China

    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.