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. 2025 Mar;42(3):419-428.
doi: 10.1007/s11095-025-03834-2. Epub 2025 Feb 26.

Combined Treatment of Metformin and Resveratrol Promotes Myogenesis Through Increased Irisin Release in C2C12 Cells

Eun Ji Seong #  1 , Yejin Kim #  1 , Zheng-Yuan Su  2 , Hee-Taik Kang  3 , Jong Hun Lee  4
Affiliations

Combined Treatment of Metformin and Resveratrol Promotes Myogenesis Through Increased Irisin Release in C2C12 Cells

Eun Ji Seong et al. Pharm Res. 2025 Mar.

Abstract

Purpose: This study aimed to investigate the additive effects of a combination of metformin and resveratrol on irisin expression in C2C12 cells.

Methods: The study involved treating C2C12 cells with metformin and resveratrol, either alone or in combination, and analyzing their effects on myogenesis and irisin release. The activation of signaling pathways, including AMPK/SIRT1/PGC1α, as well as the relative mRNA and protein expression levels of MyoD, myogenin, and Myh were also assessed.

Results: Combination treatment with metformin and resveratrol significantly increased MyoD, myogenin, Myh, and FNDC5 expression compared with the group treated with metformin alone. The increase in irisin production was associated with phosphorylation of AMPK and upregulation of PGC-1α and SIRT1, indicating activation of the AMPK/SIRT1/PGC-1α pathway. The mRNA and protein expression levels of MyoD, myogenin, and Myh were also significantly higher in the combination treatment group compared to the metformin alone group.

Conclusion: The combination of metformin and resveratrol effectively increased irisin release through the AMPK/Sirt1/PGC-1α pathway, suggesting that this combination treatment could enhance myogenesis.

Keywords: C2C12; irisin; metformin; myogenesis; resveratrol.

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Conflict of interest statement

Declarations. Conflict of Interest: The authors declare no conflict of interests.

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