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.