Table 5.
Mechanism and function of esculetin in treatment of diabetes and complications.
| Pharmacological Mechanism | Inhibition/Activation/ Downregulation/Upregulation |
Model Used | Dosage | Application | Reference |
|---|---|---|---|---|---|
| Anti-diabetic and its complications | Restore level of antioxidant enzymes (GST, COD, CAT, GPx) Increase plasma insulin in diabetic rats Decrease blood glucose in diabetic rats Decrease TBARS, lipid hydroperoxides and conjugated dienes in liver and kidney Increase vitamin C, tocopherol and reduce glutathione in kidney tissues of diabetic rats |
STZ-induced diabetes in male albino rats | 40 mg/kg | In vivo | [103] |
| Prevent increase in angiotensin II type I receptor and angiotensin II type 2 receptor expression Improve insulin sensitivity and reduce systolic blood pressure Attenuate vascular hyper-responsiveness to Angiotensin II and impair acetylcholine-mediated relaxation Decrease TGF-β and KEAP-1 expression |
HFD + STZ-induced hyperinsulinemia and hyperglycemia in male Wistar rats | 50 and 100 mg/kg | In vivo | [104] | |
| Decrease blood glucose, urea nitrogen, plasma creatinine Increase plasma albumin level Attenuate downregulation of PPARϒ in diabetic kidney and blocks TGF-β1-mediated fibronectin expression Attenuate decrease in mono-methylation (k4) and acetylation of histone H3 in diabetic kidney Decrease Bmp6 expression and increase Mmp13 expression in diabetic kidney |
STZ-induced diabetic nephropathy in Sprague Dawley rats | 50 and 100 mg/kg | In vivo | [105] | |
| Attenuate alteration in RAS, KEAP-1 and cell proliferation (Ki67) Decrease systolic blood pressure, plasma glucose, triacylglycerol and total cholesterol in insulin resistance and type 2 diabetic rats Prevent cardiac hypertrophy and cardiac fibrosis in diabetic rats Reduce AT1R, A2TR, KEAP, Ki67 and increase ACE2 expression in insulin resistance and type 2 diabetic rats Attenuate H2AK119Ub and H2BK12OUb level in heart tissue of insulin resistance and type 2 diabetic rats |
STZ-induced type diabetes and diabetic cardiomyopathy | 50 and 100 mg/kg | In vivo | [106] | |
|
Improve insulin sensitivity, hyperglycemia, and renal dysfunction Increase SOD1, GSH level and decrease TBARS levels in diabetic rats Increase angiotensin I converting enzyme 2 (ACE2) Decrease angiotensin II receptor type I and angiotensin II converting enzyme Decrease MCP-1 and TGF-β expressions in diabetic kidney Decrease H2AK119Ub expression in diabetic kidney |
HFD + STZ-induced diabetic nephropathy | 50 and 100 mg/kg | In vivo | [107] |