Endometriosis (EMs) is recorded as Zheng Jia in traditional Chinese medicine (TCM) books. Guizhi Fuling Pills (GFPs), a classic prescription for promoting blood circulation and removing blood stasis, is widely used for women's blood stasis diseases represented by Zheng Jia. At present, it has been applied to treat EMs in clinical settings. In this review, we systematically summarized the active ingredients and pharmacological mechanism of five Chinese herbs contained in GFPs and clinical applications of GFPs. The potential pathways of GFPs in the treatment of EMs were explored through network pharmacology. The current researches results indicate that the mechanisms of GFPs in the treatment of EMs mainly include acesodyne, anti-inflammation and improvement of hemodynamics. The main active compounds that are responsible for pharmacological effects in five Chinese herbs are paeonol, pachymic acid, cinnamaldehyde, amygdaloside and Paeoniflorin. This review can lay the foundation and identify the research direction for the development of GFPs as a new drug therapy for the treatment of EMs.

The active ingredients of the Chinese medical herb Paris polyphylla, P. polyphylla ethanol extract (PPE) and polyphyllin I (PPI), potentially inhibit epithelial-mesenchymal transition (EMT) in tumors. However, the roles of these ingredients in inhibiting EMT in adenomyosis (AM) remain to be explored. The primary goal of the study was to uncover the underlying molecular processes through which PPE and PPI suppress EMT in AM, alongside assessing the safety profiles of these substances. To assess the suppressive impact of PPE on adenomyosis-derived cells (AMDCs), we employed Transwell and wound healing assays. The polyphyllins (PPI, PPII, PPVII) contained in PPE were characterized using high-performance liquid chromatography (HPLC). Then, bioinformatics techniques were performed to pinpoint potential PPI targets that could be effective in treating AM. Immunoblotting was used to verify the key proteins and pathways identified via bioinformatics. Furthermore, we examined the efficacy of PPE and PPI in treating Institute of Cancer Research (ICR) mice with AM by observing the morphological and pathological features of the uterus and performing immunohistochemistry. In addition, we assessed safety by evaluating liver, kidney and spleen pathologic features and serum test results. Three major polyphyllins of PPE were revealed by HPLC, and PPI had the highest concentration. In vitro experiments indicated that PPE and PPI effectively prevent AMDCs invasion and migration. Bioinformatics revealed that the primary targets E-cadherin, N-cadherin and TGFβ1, as well as the EMT biological process, were enriched in PPI-treated AM. Immunoblotting assays corroborated the hypothesis that PPE and PPI suppress the TGFβ1/Smad2/3 pathway in AMDCs to prevent EMT from progressing. Additionally, in vivo studies showed that PPE (3 mg/kg and 6 mg/kg) and PPI (3 mg/kg and 6 mg/kg), successfully suppressed the EMT process through targeting the TGFβ1/Smad2/3 signaling pathway. Besides, it was observed that lower doses of PPE (3 mg/kg) and PPI (3 mg/kg) exerted minimal effects on the liver, kidneys, and spleen. PPE and PPI efficiently impede the development of EMT by inhibiting the TGFβ1/Smad2/3 pathway, revealing an alternative pathway for the pharmacological treatment of AM.

Objective. To explore the molecular mechanism of the Cinnamomi ramulus and Paris polyphylla Sm. (C-P) drug pair in the treatment of adenomyosis (AM) based on network pharmacology and animal experiments. Methods. Via a network pharmacology strategy, a drug-component-target-disease network (D-C-T-D) and proteinprotein interaction (PPI) network were constructed to explore the core components and key targets of C-P drug pair therapy for AM, and the core components and key targets were verified by molecular docking. Based on the results of network pharmacology, animal experiments were performed for further verification. The therapeutic effect of the C-P drug pair on uterine ectopic lesions was evaluated in a constructed AM rat model. Results. A total of 30 components and 45 corresponding targets of C-P in the treatment of AM were obtained through network pharmacology. In the D-C-T-D network and PPI network, 5 core components and 10 key targets were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the PI3K signaling pathway was the most significantly enriched nontumor pathway. Molecular docking showed that most of the core components and key targets docked completely. Animal experiments showed that the C-P drug pair significantly ameliorated the pathological changes of endometriotic lesions in AM model rats and inhibited PI3K and Akt gene expression, and PI3K and Akt protein phosphorylation. In addition, treatment with the C-P drug pair promoted AM cell apoptosis; upregulated the protein expression of Bax, Caspase-3, and cleaved Caspase-9; and restrained Bcl-2 expression. Conclusions. We propose that the pharmacological mechanism of the C-P drug pair in the treatment of AM is related to inhibition of the PI3K/Akt pathway and promotion of apoptosis in AM ectopic lesions.

Adenomyosis (AM), an estrogen-dependent chronic inflammatory disease with a rising incidence, has emerged as a major cause of infertility and reduced clinical pregnancy rates in reproductive-aged women, severely impairing reproductive health and quality of life. The core pathological mechanisms of AM are closely linked to aberrant local expression of inflammatory cytokines, including interleukin (IL)-6, C-X-C motif chemokine ligand 8 (CXCL8), IL1B, tumor necrosis factor-α, NF-κB, cyclooxygenase-2 and TGF-β, which disrupt the immune barrier at the endometrial-myometrial junction. This disruption further breaks the critical balance between proinflammatory and anti-inflammatory cytokines, ultimately fostering an immune microenvironment hostile to embryo survival. Concurrently, inflammatory cytokine-activated cellular processes, including proliferation, invasion, tissue injury and repair, epithelial-mesenchymal transition and fibrosis, further induce pathological neovascularization and impair blood perfusion in the junctional zone. These pathological changes, in turn, compromise endometrial receptivity and inhibit decidualization, ultimately resulting in implantation failure. Based on these mechanisms, key inflammatory cytokines such as IL-6, CXCL8, IL1B and IL-10 hold potential as diagnostic biomarkers for AM-related infertility and provide a theoretical basis for developing fertility-preserving therapies targeting the inflammatory cascade (such as IL-6 receptor monoclonal antibodies and TGF-β inhibitors). These findings offer new approaches to achieve the dual goals of lesion control and fertility preservation in clinical practice.

Efficacy and safety of traditional Chinese medicine on treating oligomenorrhea: a systematic review and meta-analysis Yannan Li, Guozhen Zhao, Wei Shi, Yin Zhang, Hanlin Diao, Nan Ding, Panpan Li, Fang Zhang, Lei Yang, Mengyao Sun, Hang Yu, Bo Li, Li Xu