Combination of Shengmai San and Radix puerariae ameliorates depression‐like symptoms in diabetic rats at the nexus of PI3K/BDNF/SYN protein expression

Abstract Background Hyperglycemia is a characteristic feature of diabetes that often results in neuropsychological complications such as depression. Diabetic individuals are more vulnerable to experience depression compared to the normal population. Thus, novel treatment approaches are required to reduce depressive symptoms among diabetic individuals. Traditional Chinese medicines (TCMs) such as Shengmai San (SMS) and Radix puerariae (R) are usually widely used to treat ailments such as neurological complications since ancient time. Methods In this study, SMS was combined with R to prepare an R‐SMS formulation and screened for their antidepressant activity in diabetic rats. The antidepressant potential of the prepared combination was evaluated behaviorally using open field test, novelty‐induced hypophagia, and forced swim test in diabetic rats with biochemical and protein expression (PI3K, BDNF [brain‐derived neurotrophic factor], and SYN [presynaptic vesicle protein]) analysis. Results Diabetic rats (streptozotocin, 45 mg/kg) showed elevated fasting blood glucose (FBG) >12 mM with depressive symptoms throughout the study. Treatment with R‐SMS (0.5, 1.5, and 4.5 g/kg) significantly reverted depressive symptoms in diabetic rats as evinced by significantly (p