Effect of carnosic acid on postpartum depression mouse model
Objective To determine the therapeutic effect of carnosic acid on postpartum depression mouse model.Methods Totally 70 female C57BL/6 mice were selected to undergo bilateral ovarian castration surgery,before hormone withdrawal to simulate pregnancy to create a postpartum depression model.Fifty postpartum depression model mice were screened based on the surgar preference test and randomly divided into a model control group,an estrogen group(20 μg·kg-1,sc),and low,medium,and high dose carnosic acid groups(25,50,and 100 mg·kg-1,ig).Another 10 female C57BL/6 mice that underwent sham surgery served as the sham-operated control group.The administration group was administered once a day for 28 consecutive days,at 20 mL·kg 1.After the last dose,behavioral tests such as sugar preference,forced swimming,and open field test were conducted to evaluate depression-like behaviors.Enzyme-linked immunosorbent assay(ELISA)was used to detect the fibroblast growth factor 9(FGF9)and estradiol(E2)in the serum,and 5-hydroxytryptamine(5-HT)and brain-derived neurotrophic factor(BDNF)in the hippocampal tissue.BDNF and FGF9 expressions in the mice hippocampus tissue of different groups were detected by Western blot.Hematoxylin-eosin(HE)staining was used to observe the pathological changes in the CA1 area of the mouse hippocampal tissue.Results Compared with the sham-operated control group,the surgar preference rate of the model control group was significantly decreased(P＜0.01),the immobility time of forced swimming was increased(P＜0.01),and the total distance and average speed of the mice were decreased(P＜0.01).The neuronal cells in the CA1 region of the hippocampus were scattered,with abnormal morphology and fragmentation.ELISA showed a significant decrease in the serum E2,5-HT and BDNF levels in the hippocampal tissue,and a significant increase in the serum FGF9 levels(P＜0.05 or P＜0.01).Western blot showed that the expression of BDNF protein decreased and FGF9 increased(P＜0.05 or P＜0.01).Compared with the model control group,after carnosic acid treatment,the surgar preference rate of mice in each group increased(P＜0.01).The swimming immobility time in estrogen group and carnosic acid medium and high dose groups decreased,while the total distance and average speed of movement in the open field experiment increased(P＜0.05 or P＜0.01).The pathological damage of the hippocampus was alleviated,the cells were tightly arranged,with normal morphology.The serum E2 level in the estrogen group increased significantly(P＜0.05),and the hippocampal 5-HT content increased to various degrees in the estrogen group and the carnosic acid group(P＜0.01).The content of FGF9 in the estrogen group and carnosic acid medium and high dose groups was significantly decreased(P＜0.05).The estrogen group and high dose of carnosic acid significantly increased BDNF content,up-regulated the BDNF expression level and down-regulated the FGF9 expression level(P＜0.05 orP＜0.01).Conclusion Carnosic acid obviously improves the hippocampal tissue damage and depression-like behaviors in postpartum depression mice,whose mechanism may be related to increasing hippocampal 5-HT,BDNF,and reducing FGF9 levels.
carnosic acidpostpartum depressionmechanism of actionanimal model
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