He's Yangchao Formula Ameliorates Premature Ovarian Insuf-ficiency via Remodeling Gut Microbiota to Promote Granulosa Cell Glycolysis.
10.3724/zdxbyxb-2024-0604
- Author:
Fangxuan LIN
1
;
Qing LIU
2
;
Ying ZHAO
3
;
Yun CHEN
4
,
5
;
Ruye WANG
6
;
Chenyun MIAO
5
,
7
;
Qin ZHANG
8
Author Information
1. Department of TCM Gynecology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310005, China. linlinlinfx@qq.com.
2. Department of TCM, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310013, China.
3. School of Public Health, Zhejiang Chinese Medical University, Hangzhou 310053, China.
4. Department of TCM Gynecology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310005, China. moofang560@
5. com.
6. Department of TCM Gynecology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310005, China.
7. School of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China. moofang560@
8. Department of TCM Gynecology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310005, China. 2021b027@zcmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Glycolysis;
He’s Yangchao recipe;
Intestinal flora;
Mice;
Premature ovarian insufficiency
- From:
Journal of Zhejiang University. Medical sciences
2025;():1-10
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES:To investigate the molecular mechanism by which He's Yangchao Formula improves ovarian function in premature ovarian insufficiency (POI) mice through intestinal flora modulation.
METHODS:Forty female ICR mice (aged 6-8 weeks) were intraperitoneally injected with cyclophosphamide (150 mg/kg) to establish a POI model, while 10 untreated mice served as the blank control. Successfully modeled mice were randomly divided into four groups (n=10/group): low-dose He's Yangchao Formula (6 g crude herb/kg), high-dose He's Yangchao Formula (25 g crude herb/kg), positive control (estradiol), and model control (distilled water). Treatments were admin-istered daily by gavage for 6 weeks. Vaginal exfoliated cells were stained with Wright-Giemsa solution to monitor estrous cycles. Serum estradiol and follicle-stimulating hormone (FSH) levels were measured by ELISA. Ovarian FSH receptor (FSHR) expression was assessed by immunohistochemistry. Glycolysis-related proteins pyruvate kinase M2 (PKM2) and glucose transporter 4 (GLUT4) were analyzed by Western blotting and immuno-fluorescence. Fecal samples from blank control, model control, and high-dose groups underwent metagenomic sequencing to evaluate intestinal microbiota diversity and com-position.
RESULTS:He's Yangchao Formula restored estrous cyclicity, increased serum estradiol (P<0.05), decreased serum FSH (P<0.05), and upregulated FSHR expression in granulosa cells (P<0.05). Metagenomic analysis revealed significant structural differences in intestinal flora among blank control, model control, and high-dose groups (P<0.01). The high-dose group showed reduced abundance of conditional pathogens (e.g., Alistipes, Prevotella, Odoribacter, Blautia, Rikenella) compared to the model control (P<0.05). Functional enrichment analysis indicated involvement of glycolysis-related pathways. Concordantly, PKM2 and GLUT4 expression was downregulated in the model control but upregulated in He's Yangchao Formula groups (P<0.05).
CONCLUSIONS:He's Yangchao Formula ameliorates POI in mice by remodeling intestinal flora structure, enhancing glycolytic activity, improving ovarian sex hormone secretion, increasing granulosa cell FSHR expression, and restoring estrous cyclicity.
