AUTHOR=Deng Yu , Fu Ruobing , Shang Yaqi , Hu Mengting , Xin Xirui , Hou Yubo , Yu Weixian , Liu Xinchan 

TITLE=Genipin attenuates oxidative damage in periodontal tissues by alleviating mitochondrial dysfunction and abnormal glucose uptake through inhibition of UCP2

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1446574

DOI=10.3389/fphar.2025.1446574

ISSN=1663-9812

ABSTRACT=IntroductionPeriodontitis is a chronic inflammatory disease closely associated with mitochondrial dysfunction. Uncoupling protein 2 (UCP2), located in the inner membrane of mitochondria, reduces mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) synthesis by promoting proton leakage across the membrane. This leads to decreased energy metabolism efficiency, impairing cellular glucose uptake, and disrupting intracellular energy balance. Genipin (GP), a recognized UCP2 inhibitor, exhibits anti-inflammatory and antioxidant properties. This study aimed to investigate the specific role of GP in periodontal tissue redox signaling and the potential mechanism of UCP2 in the development of periodontitis.MethodsIn this study, we constructed a model of H2O2-induced oxidative stress in human periodontal ligament cells (hPDLCs). In vivo, a rat periodontitis model was established to evaluate the effects and mechanisms of GP in alleviating oxidative damage in periodontal tissues and cells.ResultsCell experiments showed that GP effectively alleviated H2O2-induced mitochondrial dysfunction and oxidative damage in hPDLCs by inhibiting UCP2 expression and function, restoring cell viability, and reducing cell apoptosis. Additionally, GP intervention increased the expression of glucose transporter 4 (GLUT4), thereby promoting cellular glucose uptake. The results of animal experiments demonstrated that GP intervention reduced alveolar bone resorption and periodontal tissue destruction in rats with periodontitis, inhibited osteoclast differentiation, improved mitochondrial dysfunction in periodontal tissue, promoted GLUT4 expression, and reduced oxidative stress levels and cell apoptosis.DiscussionGP regulates oxidative damage in periodontal tissues by maintaining mitochondrial homeostasis, promoting glucose transporter expression, and enhancing glucose uptake, with UCP2 playing a central role.