Jiang Hai, Liu Jia, Xu Zhipeng, Song Qi, Tao Junjie, Zhu Heng, Li Qiliang, Li Lei
Department of Emergency Surgery, the First Affiliated Hospital of Bengbu Medical University, No. 287, Changhuai Road, Bengbu, 233000, Anhui Province, China.
Cell Mol Life Sci. 2025 Aug 13;82(1):311. doi: 10.1007/s00018-025-05845-z.
Acute pancreatitis (AP) is a severe inflammatory disease associated with dysregulated glycolysis and mitochondrial dysfunction. This study investigates the therapeutic potential of quercetin, a novel PFKFB3 inhibitor, in modulating glycolysis and mitochondrial function to alleviate AP.
We conducted homology analysis of the PFKFB3 protein and identified quercetin as a potential inhibitor through molecular docking. In vitro experiments using a cerulein-induced inflammatory pancreatic cell model assessed the effects of quercetin on PFKFB3 expression, glycolysis, and mitochondrial function. In vivo validation was performed using an AP rat model to evaluate the impact on inflammation, tissue damage, and metabolic status.
Quercetin significantly reduced PFKFB3 expression, inhibited glycolysis, and improved mitochondrial function in inflammatory pancreatic cells. In the AP rat model, quercetin treatment decreased serum amylase and lipase levels, reduced inflammatory markers (TNF-α and IL-6), and alleviated pancreatic tissue damage, as evidenced by histological analysis.
Quercetin effectively modulates glycolysis and mitochondrial function by inhibiting PFKFB3, thereby reducing inflammation and tissue damage in AP. These findings highlight the potential of quercetin as a novel therapeutic agent for AP.
急性胰腺炎（AP）是一种与糖酵解失调和线粒体功能障碍相关的严重炎症性疾病。本研究探讨新型磷酸果糖激酶-2/果糖-2,6-二磷酸酶3（PFKFB3）抑制剂槲皮素在调节糖酵解和线粒体功能以减轻急性胰腺炎方面的治疗潜力。
我们对PFKFB3蛋白进行了同源性分析，并通过分子对接确定槲皮素为潜在抑制剂。使用雨蛙素诱导的炎症性胰腺细胞模型进行体外实验，评估槲皮素对PFKFB3表达、糖酵解和线粒体功能的影响。使用急性胰腺炎大鼠模型进行体内验证，以评估其对炎症、组织损伤和代谢状态的影响。
槲皮素显著降低炎症性胰腺细胞中PFKFB3的表达，抑制糖酵解，并改善线粒体功能。在急性胰腺炎大鼠模型中，槲皮素治疗降低了血清淀粉酶和脂肪酶水平，降低了炎症标志物（肿瘤坏死因子-α和白细胞介素-6），并减轻了胰腺组织损伤，组织学分析证实了这一点。
槲皮素通过抑制PFKFB3有效调节糖酵解和线粒体功能，从而减轻急性胰腺炎中的炎症和组织损伤。这些发现突出了槲皮素作为急性胰腺炎新型治疗药物的潜力。
