Abstract Title:

Punicalagin protects against diabetic cardiomyopathy by promoting Opa1-mediated mitochondrial fusion via regulating PTP1B-Stat3 pathway.

Abstract Source:

Antioxid Redox Signal. 2021 Apr 28. Epub 2021 Apr 28. PMID: 33906428

Abstract Author(s):

Feng Fu, Chaoyang Liu, Rui Shi, Man Li, Min Zhang, Yanyan Du, Qiaojuan Wang, Jun Li, Guoen Wang, Jianming Pei, Mingge Ding

Article Affiliation:

Feng Fu


AIMS: This study aims to explore the efficacy of punicalagin (PG) on diabetic cardiomyopathy, with a specific focus on the mechanisms underlying the effects of PG on mitochondrial fusion/fission dynamics.

RESULTS: Cardiac structural and functional abnormalities were ameliorated in diabetic rats receiving punicalagin administration as evidenced by increased ejection fraction and attenuated myocardial fibrosis and hypertrophy. Punicalagin enhanced mitochondrial function and inhibited mitochondria-derived oxidative stress by promoting Opa1-mediated mitochondrial fusion. The benefits of PG could be abrogated by knockdown of Opa1 in vivo and in vitro. Inhibitor screening and chromatin immunoprecipitation analysis showed that Stat3 directly regulated the transcriptional expression of Opa1 by binding to its promoter and was responsible for punicalagin-induced Opa1-mediated mitochondrial fusion. Moreover, pharmmapper screening and molecular docking studies revealed that punicalagin embedded into the activity pocket of PTP1B and inhibited the activity of PTP1B. Overexpression of PTP1B blocked the promoting effect of punicalagin on Stat3 phosphorylation and Opa1-mediated mitochondrial fusion, whereas knockdown of PTP1B mimicked the benefits of punicalagin in high glucose-treated cardiomyocytes.

INNOVATION: Our study is the first to identify punicalagin as a novel mitochondrial fusion promoter against hyperglycemia-induced mitochondrial oxidative injury and cardiomyopathy by upregulating Opa1 via regulating PTP1B-Stat3 pathway.

CONCLUSION: Punicalagin protects against diabetic cardiomyopathy by promoting Opa1-mediated mitochondrial fusion, a process in which punicalagin interacts with PTP1B and inhibits its activity that in turn increases Stat3 phosphorylation and then enhances the transcriptional expression of Opa1. These results suggest that PG might be a promising new therapeutic approach against diabetic cardiac complication.

Study Type : In Vitro Study

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