Effect of Wenshen Yangxue Decoction on follicular development in aged female rats and its impact on PI3K-AKT-FOXO3a pathway
Xin Mingwei, Zhang Ying, He Junqin, Yang Wei, Wu Ying, Yin Xiaodan, Jia Zhaoxia
2019, 40(3):
344-351.
doi:10.3969/j.issn.1006-7795.2019.03.005
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Objective To explore the effect and mechanism of Wenshen Yangxue Decoction on promoting follicular development in aged female rats. Methods Eight-month-old ICR mice were randomly divided into 5 groups:A:blank group, B:controlled ovarian hyperstimulation (COH) group, C:low dose group of Wenshen Yangxue Decoction, D:middle dose group of Wenshen Yangxue Decoction, and E:high dose group of Wenshen Yangxue Decoction, and given intragastric administration for 10 days continuously at regular intervals (6:00 pm). On the 11th day, female mice in the groups B, C, D and E were intraperitoneally injected with pregnant mare serum gonadotropin (PMSG) 10 IU/mouse. Female mice in the groups A and B were intraperitoneally injected with human chorionic gonadotropin (HCG) 10 IU/mouse 48 hours later. At 14 hours later, ovaries and oviducts of mice were removed by laparotomy. After treatment, number of follicles and number of high quality follicles were examined, and the expressions of PI3K, P-PI3K, AKT, P-AKT, FOXO3a and P-FOXO3a were measured with qRT-PCR, Western blotting, and immunohistochemistry. The number of births after mating of 4 females and males was recorded for each group.Results Wenshen Yangxue Decoction could increase the number of ovulation, the number of high quality follicles and fertility of mice. Compared with blank group, the expression of PI3K mRNA in the ovary of mice in Wenshen Yangxue Decoction middle-dose group decreased, while the expression in Wenshen Yangxue Decoction high-dose and low-dose groups increased, with the difference statistically significant (P<0.05). The expression of AKT mRNA in low-dose group increased, with the difference statistically significant (P<0.05). The expression of FOXO3a mRNA in low-dose, medium-dose and high-dose groups increased, with the difference statistically significant (P<0.05), as the concentration of the TCM increased, the content of FOXO3a mRNA expression gradually decreased. Conclusion Wenshen Yangxue Decoction can promote follicular development, increase the number of ovulation, quality follicle, and embryo number in aged ICR mice by regulating the expression of PI3K, AKT and FOXO3a. Low and medium doses were found to yield the most effective results, followed by high doses.