Molecular basis of cardioprotective effects of methanol extract of Ficus exasperata in diabetic Wistar rats

Abstract

Cardiovascular complications are a significant concern in diabetes mellitus. Ficus exasperata Vahl leaf has been traditionally used for diabetes management, yet its impact on cardiovascular biomarkers in diabetic conditions remains unexplored. This study evaluated the effects of methanol extract of Ficus exasperata (MEFE) on antioxidant defense, oxidative stress markers, ion transport enzymes, inflammatory mediators, and cardiovascular gene expression in diabetic Wistar rats. Twenty Wistar rats were divided into four groups (n = 5): control, diabetic untreated, diabetes + MEFE (200 mg/kg), and diabetes + insulin (0.3 IU). Diabetes was induced with alloxan monohydrate (150 mg/kg), and treatments were administered orally for 28 days. Antioxidant enzyme activities (Glutathione peroxidase (GPx), Glutathione reductase (GR), Superoxide dismutase (SOD), Catalase, malondialdehyde and 8-hydroxy-2′-deoxyguanosine), Cardiac biomarkers (Na + /K + ATPase, Ca 2+ ATPase, Creatinine kinase-myocardial band (CK-MB), Troponin I, Troponin T, and Lactatate dehydrogenase), and gene expression of CRP, ACE, P-Selectin, and eNOS were evaluated. Data were analyzed using one-way analysis of variance, expressed as mean ± SEM, and p < 0.05 was considered statistically significant. The diabetic group treated with MEFE (200 mg/kg) significantly increased Ca²⁺ ATPase, SOD, and glutathione reductase activities compared to diabetic untreated. However, malondialdehyde and 8-OHdG levels decreased significantly in diabetes+MEFE (200 mg/kg) compared to diabetes untreated. CK-MB levels increased significantly in diabetes+MEFE (200 mg/kg) compared to diabetic untreated. MEFE reduced ACE and P-selectin expression in diabetes+MEFE (200 mg/kg) compared to diabetic untreated, indicating potential antihypertensive and anti-thrombotic effects. However, it increased CRP levels compared to control, suggesting an inflammatory response. MEFE significantly reduced eNOS expression compared to diabetic untreated, suggesting impaired vascular function. These findings suggest that while Ficus exasperata has some beneficial effects, its impact on inflammatory and cardiac biomarkers necessitates further research to fully understand its therapeutic potential and safety. • MEFE lowered ACE and P-Selectin, indicating possible antihypertensive and anti-thrombotic actions. • MEFE increased Ca²⁺ ATPase, SOD, and glutathione reductase, boosting antioxidant defense in diabetes. • MEFE reduced ACE and P-Selectin but raised CRP and lowered eNOS, suggesting mixed vascular responses.