Morin Ameliorates Myocardial Injury in Diabetic Rats via Modulation of Autophagy, Apoptosis, Inflammation, and Oxidative Stress

Figure 1. Morin prevented weight gain (a) and reduced H/B weight ratio (b) and SBP (c) in diabetic rats. The findings revealed that morin at a dose of 100 mg/kg/day prevented weight gain in diabetic animals. Moreover, the H/B weight ratio and SBP were significantly reduced when morin was administrated. Group (I) normal controls; Group II: T2DM animals; Group III: T2DM animals received 25 mg/kg/day morin, Group IV: T2DM animals received 50 mg/kg/day morin, Group (V) T2DM animals received 100 mg/kg/day morin, Group VI: positive T2DM controls received 350 mg/kg/day metformin; *: significant difference only with Group I, **: significant difference only with Group II, *#: significant difference with both Group I and Group II; the p-value<0.05 was considered significant.

Figure 2. Histopathological examination. In both Group I (A) and Group V (E) branched and anastomosed fibers were arranged in linear arrays, the nuclei were located centrally, and cardiomyocytes appeared striated. However, the histopathology of cardiac tissue in Group II and Group III (C) showed loss of anastomoses and intercalated discs with reduced striation of cardiomyocytes. Group IV (D) and Group VI (F) revealed improved striation. H&E examination was performed. Group (I) normal controls; Group II: T2DM animals; Group III: T2DM animals received 25 mg/kg/day morin, Group IV: T2DM animals received 50 mg/kg/day morin, Group (V) T2DM animals received 100 mg/kg/day morin, Group VI: positive T2DM controls received 350 mg/kg/day metformin.H&E staining was performed.

Figure 3. The analysis of lipid profile. Morin increased the levels of HDL (a) while reducing the levels of LDL (b), TG (c), and TC (d) in rats with T2DM. Group (I) normal controls; Group II: T2DM animals; Group III: T2DM animals received 25 mg/kg/day morin, Group IV: T2DM animals received 50 mg/kg/day morin, Group (V) T2DM animals received 100 mg/kg/day morin, Group VI: positive T2DM controls received 350 mg/kg/day metformin; *: significant difference only with Group I, **: significant difference only with Group II, *#: significant difference with both Group I and Group II; the p-value<0.05 was considered significant.

Figure 4. Morin improved glycemic profile in diabetic rats. The findings demonstrated that morin ameliorated GTT (a), ITT (b), and blood glucose levels (c) when administrated to diabetic animals. Group (I) normal controls; Group II: T2DM animals; Group III: T2DM animals received 25 mg/kg/day morin, Group IV: T2DM animals received 50 mg/kg/day morin, Group (V) T2DM animals received 100 mg/kg/day morin, Group VI: positive T2DM controls received 350 mg/kg/day metformin; *: significant difference only with Group I, **: significant difference only with Group II, *#: significant difference with both Group I and Group II; the p-value<0.05 was considered significant.

Figure 5. Apoptosis in cardiac tissue. The expression of BCL-2 at gene (a) and protein (d) levels were increased when morin was administrated to diabetic animals, whereas CASP-3 (b) and e) and CASP-9 (c and f) gene and protein levels were reduced upon morin administration. Group (I) normal controls; Group II: T2DM animals; Group III: T2DM animals received 25 mg/kg/day morin, Group IV: T2DM animals received 50 mg/kg/day morin, Group (V) T2DM animals received 100 mg/kg/day morin, Group VI: positive T2DM controls received 350 mg/kg/day metformin; *: significant difference only with Group I, **: significant difference only with Group II, *#: significant difference with both Group I and Group II, ns: significant difference neither with Group I nor with Group II; the p-value<0.05 was considered significant.

Figure 6. Morin promoted autophagy in cardiac tissue. Gene and protein levels of p62 (a and d), LC3 (b and e), and BECN1 (c and f) were analyzed. Group (I) normal controls; Group II: T2DM animals; Group III: T2DM animals received 25 mg/kg/day morin, Group IV: T2DM animals received 50 mg/kg/day morin, Group (V) T2DM animals received 100 mg/kg/day morin, Group VI: positive T2DM controls received 350 mg/kg/day metformin; *: significant difference only with Group I, **: significant difference only with Group II, *#: significant difference with both Group I and Group II; the p-value<0.05 was considered significant.

Figure 7. The levels of cardiac markers. Morin reduced the levels of troponin T (a), CK-MB (b), MMP-9 (c), and TGF-β1 (d) in rats with diabetes. Group (I) normal controls; Group II: T2DM animals; Group III: T2DM animals received 25 mg/kg/day morin, Group IV: T2DM animals received 50 mg/kg/day morin, Group (V) T2DM animals received 100 mg/kg/day morin, Group VI: positive T2DM controls received 350 mg/kg/day metformin; *: significant difference only with Group I, **: significant difference only with Group II, *#: significant difference with both Group I and Group II; the p-value<0.05 was considered significant.