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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<\/jats:italic> (R) are usually widely used to treat ailments such as neurological complications since ancient time.<\/jats:p><\/jats:sec>Methods<\/jats:title>In this study, SMS was combined with R to prepare an R\u2010SMS 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\u2010induced hypophagia, and forced swim test in diabetic rats with biochemical and protein expression (PI3K, BDNF [brain\u2010derived neurotrophic factor], and SYN [presynaptic vesicle protein]) analysis.<\/jats:p><\/jats:sec>Results<\/jats:title>Diabetic rats (streptozotocin, 45\u2009mg\/kg) showed elevated fasting blood glucose (FBG) >12\u2009mM with depressive symptoms throughout the study. Treatment with R\u2010SMS (0.5, 1.5, and 4.5\u2009g\/kg) significantly reverted depressive symptoms in diabetic rats as evinced by significantly (p<\/jats:italic>\u2009<\u20090.05) reduced immobility time with an increased tendency to eat food in a novel environment. Treatment with R\u2010SMS also significantly increased the protein expression of PI3K, BDNF, and SYN protein, which play a crucial role in depression.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>This study showed that R\u2010SMS formulation antagonized depressive symptoms in diabetic rats; thus, this formulation might be studied further to develop as an antidepressant.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ame2.12333","type":"journal-article","created":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T04:40:35Z","timestamp":1686804035000},"page":"211-220","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Combination of Shengmai San and Radix puerariae<\/i> ameliorates depression\u2010like symptoms in diabetic rats at the nexus of PI3K\/BDNF\/SYN protein 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