Synergistic effect of isoflavones and Inonotus obliquus (chaga) extract on streptozotocin induced type II diabetes rats

Current antidiabetic therapies are plagued with severe long-term contraindications. This makes new, viable, long-term treatment options for type 2 diabetes important to tackle the increasing global burden of diabetes and its associated complications. This thesis investigates the synergistic effects of naturally occurring, isoflavone-rich kudzu extract and extract from Inonotus obliquus (chaga) in the treatment of diabetes. A method to isolate isoflavones from kudzu root using a tailor-made green solvent, natural deep eutectic solvents, was developed. The effect of the green solvent on the antioxidant of the isolated isoflavone-rich extract was investigated using electron paramagnetic resonance (EPR). The effect of two treatment doses (100 mg/kg and 200 mg/kg) in induced diabetes in rodents was assessed. We found significant improvement in hepatic and renal function in diabetic rats treated with the isoflavone-rich kudzu extract at dose of 200mg/kg, aspartate transaminase level of 14.9±2.1 U/L compared to 21±2.4U/L (p<0.05) in untreated diabetic rats; alanine transaminase level of 7.9±1.4U/L compared to 16.3±2.6U/L (p<0.05) in untreated diabetic rats; and blood urea nitrogen level of 4.9±0.6 mmol/L compared to 8.2±1.2mmol/L (p<0.05) in untreated diabetic rats. Also, treatment with the isoflavone-rich kudzu extract at dose of 200mg/kg decreased platelet count from 948±106.8×103 U/L in untreated diabetic rats to 762 ±18.9 ×103 U/L. Also fasting blood glucose (FBG) and glycated haemoglobin level were significantly lower in diabetic rats treated with the isoflavone-rich kudzu extract in a dose-dependent manner compared to untreated diabetic rats. We also found enhanced regeneration of pancreatic β-cell in diabetic rats treated with the isoflavone-rich kudzu extract and no toxic effect in control rats treated with the same extract. We further explored the treatment benefits of Inonotus obliquus (chaga extract), isoflavone-rich kudzu extract, and chaga and isoflavone-rich kudzu extract in induced diabetic rodents. Our findings are that plasma levels of insulin in diabetic rats with chaga extract (136.3±45.7 μlU/mL; p= 0.001), isoflavone-rich kudzu extract (103.9±18.5 μlU/mL; p= 0.124) and chaga and isoflavone-rich kudzu extract (91.12±41.7 μlU/mL; p= 0.499) were improved compared to diabetic rats (77.9±31.0 μlU/mL). Chaga extract, isoflavone-rich kudzu extract, and chaga and isoflavone-rich kudzu extract treatment all lowered FBG level in diabetic rats. Also, the gene expression of insulin in pancreatic tissue in diabetic rats treated with isoflavone-rich kudzu extract (0.16±0.21 AU/µm2; p=0.0041), chaga extract (0.22±0.14 AU/µm2; p<0.0001), or chaga and isoflavone-rich kudzu extract (0.19±0.19 AU/µm2; p= 0.0028) was improved compared to untreated diabetic rats (0.05±0.16 AU/µm2). Body weight was also improved with chaga (538±57g; p=0.0234), isoflavone-rich kudzu extract (521±38g; p=0.11), and chaga and isoflavone-rich kudzu extract and (500±73g; p=0.63) treatment compared to diabetic rats (449±23g). Although cardiovascular indices; particularly pulse wave velocity, arterial biomechanical properties, blood pressure, left ventricular haemodynamics, and vasoreactivity of isolated vessels were not altered with our present diabetes model as we hypothesized, our findings are important as it interrogates our understanding on the manifestation of cardiovascular complications in diabetic subjects independent of high blood pressure. My findings would contribute to the effective use of naturally occurring compounds in the treatment of diabetes and its associated complications.