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

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 < 0.05) reduced immobility time with an increased tendency to eat food in a novel environment. Treatment with R‐SMS also significantly increased the protein expression of PI3K, BDNF, and SYN protein, which play a crucial role in depression. CONCLUSION: This study showed that R‐SMS formulation antagonized depressive symptoms in diabetic rats; thus, this formulation might be studied further to develop as an antidepressant.