Improved Renoprotection in Diabetes with Combination Therapy of Coccinia indica Leaf Extract and Low-Dose Pioglitazone

Background: The metabolic changes associated with diabetes can lead to nephropathy eventually resulting in end-stage renal disease. Current antidiabetic therapies do not effectively prevent the onset of diabetic kidney diseases as well as progression. Aim: To evaluate the effect of Coccinia indica leaf extract alone and in combination with pioglitazone, an antihyperglycemic agent was used to modulate the progressive kidney damage induced by type 2 diabetes in rats. Hypotheses: Pioglitazone causes severe adverse effects when administered for long-term therapy. The hypotheses in this study is to examine the renoprotective effect of Coccinia indica leaf extract (200 mg/kg p.o.) when co-administered with low-dose pioglitazone (7 mg/kg) in type-2-diabetes-induced nephropathy in rats and simultaneously evaluate the hypoglycemic response as well. Methods: Rats (Males, Sprague Dawley) were kept on a high-fat diet and were given a single dose of streptozotocin (35 mg/kg, i.p.) to induce diabetic nephropathy. Treatment groups received either Coccinia indica leaf extract or pioglitazone or pioglitazone with Coccinia indica extract, fenofibrate, or lisinopril for 7 weeks. Blood glucose, antioxidant status, triglycerides, total cholesterol, creatinine, blood urea nitrogen, and proteinuria levels were estimated and compared with the normal control and disease control (untreated) groups. Results: The untreated diabetic rats showed increased blood glucose levels, lipid profiles, and renal oxidative stress, along with an increase in nephropathy markers such as blood urea nitrogen, creatinine, and proteinuria. Histopathological examination revealed glomerular damage. Combination treatment with Coccinia indica leaf extract and a low dose of pioglitazone normalized the nephropathic markers as well as histopathological changes. Conclusion: Coccinia indica leaf extract when co-administered with a low dose of pioglitazone as antidiabetic therapy showed good glycemic control and a beneficial renoprotective effect. Combination therapy would lower the dose of pioglitazone and also protect kidneys from drug-induced toxicity as observed from normalized nephropathic markers in a diabetic rat model.