Berberine inhibits NLRP3 inflammasome activation by regulating mTOR/ mtROS axis to alleviate diabetic cardiomyopathy

作者：Zhong, Changsheng; Xie, Yilin; Wang, Huifang; Chen, Wenxian; Yang, Zhenbo; Zhang, Lei; Deng, Qin; Cheng, Ting; Li, Mengyang; Ju, Jin; Liu, Yanyan^*; Liang, Haihai^*

来源：European Journal of Pharmacology, 2024, 964: 176253.

DOI：10.1016/j.ejphar.2023.176253

• Berberine
• mTOR
• mtROS
• NLRP3 inflammasome
• Diabetic cardiomyopathy

Diabetes cardiomyopathy (DCM) refers to myocardial dysfunction and disorganization resulting from diabetes. In this study, we investigated the effects of berberine on cardiac function in male db/db mice with metformin as a positive control. After treatment for 8 weeks, significant improvements in cardiac function and a reduction in collagen deposition were observed in db/db mice. Furthermore, inflammation and pyroptosis were seen to decrease in these mice, as evidenced by decreased expressions of p-mTOR, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), IL-1 beta, IL-18, caspase-1, and gasdermin D (GSDMD). In vitro experiments on H9C2 cells showed that glucose exposure at 33 mmol/L induced pyroptosis, whereas berberine treatment reduced the expression of p-mTOR and NLRP3 inflammasome components. Moreover, berberine treatment was seen to inhibit the generation of mitochondrial reactive oxygen species (mtROS) and effectively improve cell damage in high glucose-induced H9C2 cells. The mTOR inhibitor, Torin-1, showed a therapeutic effect similar to that of berberine, by reducing the expression of NLRP3 inflammasome components and inhibiting mtROS gen-eration. However, the activation of mTOR by MHY1485 partially nullified berberine's protective effects during high glucose stress. Collectively, our study reveals the mechanism that berberine regulates the mTOR/mtROS axis to inhibit pyroptosis induced by NLRP3 inflammasome activation, thereby alleviating DCM.

• 单位
  哈尔滨医科大学