Network and experimental pharmacology on mechanism of Si-Wu-tang improving ovarian function in a mouse model of premature ovarian failure induced by cyclophosphamide

Xia Liu; Yufan Song; Fanru Zhou; Chu Zhang; Fan Li; Runan Hu; Wenwen Ma; Kunkun Song; Zhouping Tang; Mingmin Zhang

doi:10.1016/j.jep.2022.115842

Network and experimental pharmacology on mechanism of Si-Wu-tang improving ovarian function in a mouse model of premature ovarian failure induced by cyclophosphamide

J Ethnopharmacol. 2023 Jan 30:301:115842. doi: 10.1016/j.jep.2022.115842. Epub 2022 Oct 18.

Authors

Xia Liu¹, Yufan Song², Fanru Zhou³, Chu Zhang⁴, Fan Li⁵, Runan Hu⁶, Wenwen Ma⁷, Kunkun Song⁸, Zhouping Tang⁹, Mingmin Zhang¹⁰

Affiliations

¹ Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: xlhust2012@163.com.
² Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: songyufan23@163.com.
³ Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: 649985078@qq.com.
⁴ Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: d201881651@hust.edu.cn.
⁵ Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: m201875894@hust.edu.cn.
⁶ Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: m201976098@hust.edu.cn.
⁷ Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: wwmahusttj@163.com.
⁸ Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: 1393137368@qq.com.
⁹ Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: ddjtzp@163.com.
¹⁰ Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: mmzhangeins@163.com.

PMID: 36265674
DOI: 10.1016/j.jep.2022.115842

Abstract

Ethnopharmacological relevance: Si-Wu-Tang (SWT) has become a common basic prescription for supplementing blood and regulating menstruation, and enjoys the reputation of "the first prescription in gynecology". It is often reported in the treatment of premature ovarian failure (POF). However, knowledge of its specific mechanism is still limited.

Aim of the study: This study aimed to identify the potential effects and underlying mechanisms of SWT on POF.

Materials and methods: After confirming the therapeutic effect of SWT on POF mice induced by cyclophosphamide, we further clarified the promoting effect of SWT on ovarian follicle development by detecting the expression of key factors related to follicle development in the ovary in different ways.Then, network pharmacology and gene expression profiling of POF from the GEO database were used to clarify the underlying mechanisms. Molecular biology and molecular docking analysis were applied for final mechanism verification.

Results: Our results showed that SWT increased body weight, ovarian index, reversed disordered serum hormone levels, and menstrual cycle in POF mice. After SWT treatment, the number of follicles at all levels in mice with POF also recovered. Using molecular biology techniques, it was proven that SWT can improve follicle development and angiogenesis in the microenvironment. The network pharmacology and gene expression profiling from the GEO database indicated that the PI3K/Akt signaling pathway may be the reason why SWT improves ovarian function in mice with POF. Subsequently, further Western blot and immunoprecipitation indicated that SWT indeed inhibited the PI3K/Akt signaling pathway in mice with POF. In addition, this conclusion was further confirmed by molecular docking experiments.

Conclusions: SWT can improve ovarian function in POF mice induced by cyclophosphamide, and its mechanism is related to the inhibition of the PI3K/Akt signaling pathway.

Keywords: Cyclophosphamide; PI3K/Akt pathway; Premature ovarian failure; Si-Wu-Tang.

MeSH terms

Animals
Cyclophosphamide / toxicity
Disease Models, Animal
Female
Humans
Menopause, Premature*
Mice
Molecular Docking Simulation
Phosphatidylinositol 3-Kinases / metabolism
Primary Ovarian Insufficiency* / chemically induced
Primary Ovarian Insufficiency* / drug therapy
Proto-Oncogene Proteins c-akt / metabolism

Substances

si-wu-tang
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
Cyclophosphamide