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 < 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.

Keywords: BDNF; STZ induced diabetes; Shengmai San; depression; traditional Chinese medicine.

FIGURE 1

Experimental design.

FIGURE 2

Effect of R‐SMS (Shengmai San and Radix puerariae) on weight and biochemical parameter of control, diabetic, R‐SMS, and DNZ (donepezil) treated rats. (A) Sugar change among rats in STZ (streptozotocin) and treated groups compared to the control rats. (B) Weight change after STZ administration. (C) Ratio of lipid profile in STZ‐administered rats compared to normal rats. (D) Ratio of lipid profile in R‐SMS‐ and DNZ‐treated rats compared to STZ‐administered rats. Each bar represents value as means ± SEM. n = 8 rats per group. Statistical significance of the data is represented as *p < 0.05, **p < 0.01, and ***p < 0.001 compared with the STZ model.

FIGURE 3

Effect of R‐SMS (Shengmai San and Radix puerariae) on rat autonomic activity using open field arena among control, diabetic, R‐SMS, and DNZ (donepezil) treated rats. (A) Rest and movement time. (B) Average speed. (C) Average distance traveled. (D) Distance moved in the central area. (E) Pictorial view of rat movement in the open field arena. Data are expressed as mean ± SEM. n = 8 in each group. *p < 0.05 and **p < 0.001 compared with the diabetic model.

FIGURE 4

Effect of R‐SMS (Shengmai San and Radix puerariae) on novel inhibition of feeding in rats. Each bar is expressed as mean ± SEM. n = 8 animals in each group. Statistical significance is represented as ***p < 0.001 compared with the diabetic model.

FIGURE 5

Effect of R‐SMS (Shengmai San and Radix puerariae) on diabetic rats on forced swim test. Each bar is expressed as mean ± SEM. n = 8 animals in each group. Statistical significance is represented as *p < 0.05, **p < 0.01, and ***p < 0.001 compared with the diabetic model.

FIGURE 6

Effect of R‐SMS (Shengmai San and Radix puerariae) on diabetic rats' hippocampal BDNF (brain‐derived neurotrophic factor) protein level. Each bar is expressed as mean ± SEM. n = 8 animals in each group. Statistical significance is represented as *p < 0.05, **p < 0.01, and ***p < 0.001 compared with the diabetic model.

FIGURE 7

Effects of R‐SMS (Shengmai San and Radix puerariae) on hippocampal PI3K and SYN (presynaptic vesicle protein) expression in diabetic rats. (A) Western blot image of PI3K and SYN expression. (B) Differential expression of PI3K. (C) Differential expression of SYN in diabetic and treated rats. Statistical significance of the date is represented as *p < 0.05, **p < 0.01, and ***p < 0.001 compared to the diabetic group.