Dihydromyricetin Improves Myocardial Functioning by Influencing Autophagy Through SNHG17/Mir-34a/SIDT2 Axis.

BACKGROUND

Diabetic cardiomyopathy (DCM) is a common and severe complication of Diabetes Mellitus (DM). Dihydromyricetin (DHM) is a flavonoid compound with potential cardioprotective effects, but the mechanism of DHM in diabetes-induced myocardial damage and autophagy is not fully understood.

OBJECTIVE

The objective of this study is to evaluate the effects of DHM on cardiac function and pathological features of DCM, with a particular focus on its impact on the SNHG17/miR-34a/SIDT2 pathway.

METHODS

In vivo experiments: After constructing the DM mice model, it was treated with different doses of DHM. Masson's staining and collagen deposition/fibrosis markers were used to evaluate the effect of DHM on cardiac fibrosis in DM mice. In vitro experiments: 3-[4,5- dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were used to determine the influence of DHM on cell viability and apoptosis, respectively, in high glucose-induced HL-1 cells. Enzyme-labeled Immunosorbent Assay was used to detect levels of cardiac enzyme and inflammation-related factors, while Western blot analyzed the levels of AMPK/mTOR and autophagy-related proteins.

RESULTS

DHM significantly improved cardiac function in DM and reduced Renin-angiotensin-aldosterone system markers, alongside decreasing markers of cardiomyocyte damage. DHM mitigated myocardial fibrosis, inflammatory marker levels, and autophagy dysregulation while upregulating lncRNA SNHG17 expression. Mechanistically, DHM acted through the SNHG17/miR-34a/SID1 transmembrane family member 2 (SIDT2) axis, reducing miR-34a expression and restoring SIDT2-mediated autophagy balance, ultimately alleviating apoptosis, inflammation, and fibrosis in diabetic cardiac tissue and high-glucose-induced HL-1 cells.

CONCLUSION

DHM improves cardiac function and mitigates DCM progression by targeting the SNHG17/miR-34a/SIDT2 regulatory axis, thereby reducing inflammation, fibrosis, and autophagy dysregulation. These findings provide mechanistic insights into DHM’s cardioprotective effects, supporting its potential as a therapeutic agent for DCM.