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. 2025 Jun 27;56(4):207.
doi: 10.1007/s10735-025-10453-z.

Theaflavin-3,3'-digallate protects against myocardial ischemia/reperfusion injury and hypoxia/reoxygenation injury by activating the PI3K/Akt/mTOR pathway

Sha Wang #  1 , Huijun Wang #  2
Affiliations

Theaflavin-3,3'-digallate protects against myocardial ischemia/reperfusion injury and hypoxia/reoxygenation injury by activating the PI3K/Akt/mTOR pathway

Sha Wang et al. J Mol Histol. .

Abstract

Myocardial ischemia followed by reperfusion triggers a range of pathological events, among which excessive autophagy plays a key role. Theaflavin-3,3'-digallate (TF3) is a functional polyphenol of black tea and is beneficial in the prevention or/and treatment of various diseases. Here, we explored the therapeutic effect of TF3 on myocardial ischemia/reperfusion (I/R) injury. I/R injury was induced in rats through ischemia (30 min) followed by reperfusion (24 h). TF3 was administered seven days before the I/R. Cardiac function was determined by echocardiography. Infarct size and apoptosis were assessed using TTC and TUNEL, respectively. H9C2 cardiomyocytes were treated with TF3 or/and PI3K inhibitor (LY294002) and then exposed to hypoxia/reoxygenation (H/R). Content levels of myocardial injury indicators in rat hearts and H9C2 cardiomyocytes were detected using corresponding kits. H9C2 cardiomyocyte apoptosis was evaluated by flow cytometry. Protein levels of autophagy, apoptosis, and PI3K/Akt/mTOR signaling in vivo and in vitro were detected using western blotting. TF3 reduced myocardial infarct size and decreased serum CK-MB, cTnT, and LDH content levels in rat model of myocardial I/R. TF3 reduced apoptosis and autophagy in I/R rat hearts and H9C2 cardiomyocytes by reducing Bax, cleaved caspase-3, Beclin-1, and LC3B levels, and elevating Bcl-2 and p62 levels. TF3 administration activated PI3K/Akt/mTOR signaling in I/R rat hearts and H9C2 cells. PI3K inhibitor LY294002 reversed the inhibitory effect of TF3 on H/R-induced apoptosis and autophagy in H9C2 cells. Overall, TF3 alleviates I/R-induced myocardial injury by reducing autophagy and apoptosis by activating PI3K/Akt/mTOR signaling.

Keywords: Autophagy; Myocardial ischemia/reperfusion; PI3K/Akt; Theaflavin-3,3′-digallate.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: The experimental procedures and animal care were approved by the Animal Ethics Committee of Hubei Provincial Center for Disease Control and Prevention (Safety Evaluation Research Center Animal Welfare No. 202320113; July 12th, 2023). Consent to participate: Not applicable. Consent to publish: Not applicable.

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