Berberine blocks inflammasome activation and alleviates diabetic cardiomyopathy via the miR‑18a‑3p/Gsdmd pathway

Yang,Lin; Cheng,Chun-Feng; Li,Zhi-Fang; Huang,Xiao-Jing; Cai,Shao-Qing; Ye,Shan-Yu; Zhao,Li-Jun; Xiong,Yi; Chen,Dong-Feng; Liu,He-Lu; Ren,Zhen-Xing; Fang,Hong-Cheng

doi:10.3892/ijmm.2023.5252

Berberine blocks inflammasome activation and alleviates diabetic cardiomyopathy via the miR‑18a‑3p/Gsdmd pathway

Authors:
- Lin Yang
- Chun-Feng Cheng
- Zhi-Fang Li
- Xiao-Jing Huang
- Shao-Qing Cai
- Shan-Yu Ye
- Li-Jun Zhao
- Yi Xiong
- Dong-Feng Chen
- He-Lu Liu
- Zhen-Xing Ren
- Hong-Cheng Fang
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Affiliations: Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong 518104, P.R. China, Biomedical Research Institute, The Hong Kong University of Science and Technology Medical Center, Shenzhen Peking University, Shenzhen, Guangdong 518036, P.R. China, Department of Anatomy, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China
Published online on: April 24, 2023 https://doi.org/10.3892/ijmm.2023.5252
Article Number: 49

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Abstract

Diabetic cardiomyopathy (DCM) is a cardiovascular disease which has been reported as a major cause of mortality worldwide for several years. Berberine (BBR) is a natural compound extracted from a Chinese herb, with a clinically reported anti‑DCM effect; however, its molecular mechanisms have not yet been fully elucidated. The present study indicated that BBR markedly alleviated DCM by inhibiting IL‑1β secretion and the expression of gasdermin D (Gsdmd) at the post‑transcriptional level. Considering the importance of microRNAs (miRNAs/miRs) in the regulation of the post‑transcriptional process of specific genes, the ability of BBR to upregulate the expression levels of miR‑18a‑3p by activating its promoter (‑1,000/‑500) was examined. Notably, miR‑18a‑3p targeted Gsdmd and abated pyroptosis in high glucose‑treated H9C2 cells. Moreover, miR‑18a‑3p overexpression inhibited Gsdmd expression and improved biomarkers of cardiac function in a rat model of DCM. On the whole, the findings of the present study indicate that BBR alleviates DCM by inhibiting miR‑18a‑3p‑mediated Gsdmd activation; thus, BBR may be considered a potential therapeutic agent for the treatment of DCM.

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