2. Academic Validation
  3. Berberine inhibits NLRP3 inflammasome activation by regulating mTOR/mtROS axis to alleviate diabetic cardiomyopathy

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

  • Eur J Pharmacol. 2023 Dec 12:176253. doi: 10.1016/j.ejphar.2023.176253.
Changsheng Zhong 1,  Yilin Xie 2,  Huifang Wang 1,  Wenxian Chen 1,  Zhenbo Yang 1,  Lei Zhang 1,  Qin Deng 3,  Ting Cheng 1,  Mengyang Li 1,  Jin Ju 2,  Yanyan Liu 4,  Haihai Liang 5
Affiliations

Affiliations

  • 1 School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, 518055, China.
  • 2 School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Guangdong, 518055, China.
  • 3 School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Guangdong, 518055, China.
  • 4 Zhuhai People's Hospital, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai, 519000, Guangdong, China. Electronic address: [email protected].
  • 5 Zhuhai People's Hospital, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai, 519000, Guangdong, China; Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China. Electronic address: [email protected].
PMID: 38096968 DOI: 10.1016/j.ejphar.2023.176253
Abstract

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-1β, 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 generation. 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.

Keywords

Berberine; Diabetic cardiomyopathy; NLRP3 inflammasome; mTOR; mtROS.

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