Abstract
Objective To explore the molecular network mechanism of modified Taohong Siwu Decoction (MTHSWD) to interfere with premature ovarian failure based on systematic pharmacological strategy. Methods The network pharmacology strategy was used to explore the potential mechanism of MTHSWD intervention in POF, and then it was verified through animal experiments. Mouse zona pellucida 3 was used as an antigen to subcutaneously immunize BALB/c female mice to establish an immune POF model. Mice were divided into MTHSWD low-, medium-, and high-dose groups, positive control group, model group, and normal group. After 30 days of drug intervention, ovarian tissue was taken for pathological hematoxylin-eosin (HE) staining, and immunohistochemical methods were used to detect the expression of TGF-β1 and TGF-βRII and Smad2/3 protein expression in follicular wall granular cells and ovarian tissue, respectively. Results Network pharmacology studies have shown that MTHSWD may interfere with the TGF-β signaling pathway. Animal experimental research shows that, compared with the model group, the number of ovarian mature follicles in the MTHSWD groups and the positive group was significantly increased, and the number of atresia follicles decreased. Immunohistochemistry showed that, compared with the control group, the expression of TGF-β1, TGF-βRII, and Smad2/3 in the follicular wall granulosa cells and ovarian tissues of MTHSWD groups was significantly higher than that of the model group (P < 0.05). Conclusion MTHSWD may improve the ovarian function of POF mice by upregulating the protein expression of granulosa cells TGF-β1, TGF-βRII, and Smad2/3.
Highlights
Premature ovarian failure (POF) refers to a disease that causes amenorrhea, infertility, menopause, and genitourinary symptoms before the age of 40 due to ovarian failure [1]
Potential Compounds and Targets of modified Taohong Siwu Decoction (MTHSWD) and POF Gene Collection. e potential components and targets of MTHSWD were searched from TCMSP [30] according to the pharmacokinetic parameters of chemical components (absorption, distribution, metabolism, and excretion (ADME)). e standard was oral bioavailability (OB) ≥ 30%, Caco-2 parameter > −0.4, and drug-like activity (DL) ≥ 0.18 [30]. e POF genes were collected to search the Online Mendelian Inheritance in Man (OMIM, http://omim.org/) [31] and GeneCards [32]. e official gene symbol of MTHSWD potential targets and POF genes were collected from UniProt KB, with the species restricted to human (Table S1 and Table S2)
A total of 247 MTHSWD potential targets were obtained and 754 POF genes were collected from OMIM and GeneCards
Summary
Premature ovarian failure (POF) refers to a disease that causes amenorrhea, infertility, menopause, and genitourinary symptoms before the age of 40 due to ovarian failure [1]. Epidemiological studies have shown that the incidence rate in women is about 1% [1, 2]. Hormone replacement therapy (HRT) is the most popular choice for women with POF to get rid of menopausal syndrome [4]. HRT has its own indications and contraindications [5]. With the increase of clinical evidence, TCM has shown a good effect in the treatment of POF [8,9,10]. E systematic review and meta-analysis of Bushen Huoxue (nourishing the kidney and promoting blood circulation) Chinese herbal medicine for POF showed that compared with the western medicine group, Chinese medicine may improve the total effective rate, menstrual improvement rate, symptom score improvement, and so on, and the incidence of adverse With the increase of clinical evidence, TCM has shown a good effect in the treatment of POF [8,9,10]. e systematic review and meta-analysis of Bushen Huoxue (nourishing the kidney and promoting blood circulation) Chinese herbal medicine for POF showed that compared with the western medicine group, Chinese medicine may improve the total effective rate, menstrual improvement rate, symptom score improvement, and so on, and the incidence of adverse
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