What question did this study set out to answer?

This research investigates the potential of Sappanone A to alleviate diabetic cardiomyopathy by promoting lysosomal autophagy via TFEB activation.

May 10, 2026

Sappanone A targets TFEB to promote lysosomal autophagy and attenuate high glucose-induced myocardial injury

Puntos clave

This research investigates the potential of Sappanone A to alleviate diabetic cardiomyopathy by promoting lysosomal autophagy via TFEB activation.
In vitro: H9c2 cardiomyocytes treated with high glucose and Sappanone A, assessing cell viability and apoptosis.
In vivo: STZ-induced DCM mice received Sappanone A (10 mg/kg/day for 8 weeks), with evaluations of cardiac function and autophagy markers.
Mechanistic validation using TFEB-knockout models and the autophagy inhibitor chloroquine.
Sappanone A improved survival of high glucose-injured cardiomyocytes, reduced apoptosis and reactive oxygen species.
In DCM mice, Sappanone A enhanced ejection fraction, decreased fibrosis, and restored autophagy flux.
Treatments were ineffective in TFEB-knockout models or with chloroquine co-treatment, confirming the TFEB-dependent mechanism.

Resumen

Introduction: Diabetic cardiomyopathy (DCM) involves myocardial injury under hyperglycemia, where impaired autophagy and oxidative stress play critical roles. This study explores whether Sappanone A (a natural compound) alleviates DCM by activating TFEB-mediated lysosomal autophagy. Methods: In vitro: H9c2 cardiomyocytes were injured with high glucose and treated with Sappanone A. Cell viability (CCK-8), apoptosis (flow cytometry), ROS (DCFHDA), and autophagy markers (LC3-II/I, p62, LAMP1 via WB/qPCR) were assessed. In vivo: STZ-induced DCM mice received Sappanone A (10 mg/kg/day, 8 weeks). Cardiac function (echocardiography), serum ANP/BNP (ELISA), histopathology (H&E/Masson), and autophagy flux (TFEB/LAMP1) were analyzed. TFEB-knockout models and chloroquine (CQ, autophagy inhibitor) validated mechanistic links. Results: Sappanone A dose-dependently enhanced HG-injured cardiomyocyte survival, reduced apoptosis and ROS, while upregulating TFEB nuclear translocatiandlysosomal function.In DCM mice, it improved ejection fraction, reduced fibrosis, and restored autophagic flux.These effects were abolished in TFEB-knockout models or with CQ co-treatment, confirming TFEB-dependent autophagy as the core mechanism. Conclusion: Sappanone A protects against DCM by activating TFEB-driven lysosomal autophagy, mitigating oxidative stress, and preserving cardiac function. It represents a novel therapeutic candidate for DCM.

Me gusta

Guardar

Cite This Study

Zhang et al. (Fri,) studied this question.

synapsesocial.com/papers/6a0021cdc8f74e3340f9cc92 https://doi.org/https://doi.org/10.1159/000551971

Me gusta

Guardar