Polycystic ovary syndrome (PCOS), affecting 5 %–18 % of women globally (Joham et al., 2022) and approximately 7.8 % in China (Yang et al., 2022), represents a significant public health challenge due to its association with infertility, as well as endocrine and metabolic dysfunctions in women of reproductive age. The clinical manifestations of PCOS include irregular menstruation, oligo-ovulation or anovulation, biochemical hyperandrogenemia, and clinical manifestations of hyperandrogenemia and polycystic ovaries. Studies have shown that approximately 50 % of PCOS patients are overweight or obese (Lim et al., 2012), with 50 %–70 % exhibiting insulin resistance (Zippl et al., 2021). There are currently no authorized treatment medications for PCOS. The basic treatments for PCOS are reducing insulin resistance, lowering testosterone, and promoting ovulation. However, all these medications are off-label drugs and are prone to a series of adverse outcomes such as high ovulation rates, increased miscarriage rates, and low pregnancy rates (Bjekic-Macut et al., 2021). Additionally, PCOS patients are at an elevated risk of developing type 2 diabetes (T2MD), cardiovascular disease, and gynecological tumors (Anagnostis et al., 2018). As a result, the development of novel medications for the treatment of PCOS has become an urgent need for women's reproductive health and socioeconomic advancement.

Traditional Chinese medicine (TCM) has unique perspectives and extensive clinical experience in the treatment of PCOS(Fu et al., 2024). In the theory of traditional Chinese medicine, PCOS is classified into the categories of menstrual irregularities, delayed menstruation, and amenorrhea. TJZL is an evidence-based traditional Chinese medicine formula derived from the Tang Dynasty's Beiji Qianjin Yaofang and has been refined through years of clinical application. This formulation is characterized by its functions of clearing Liver fire, eliminating damp-heat, and regulating menstruation. It is clinically used to treat gynecological disorders such as delayed menstruation and amenorrhea (Liang, 2024; Shang, 2025). Moreover, preclinical research confirms that TJZL is effective in ameliorating ovarian morphology and sex hormone metabolic disorders in PCOS rat models (Duan et al., 2023). The composition of Chinese herbal medicines in the TJZL formula includes: Lycium barbarum L., Bupleurum chinense DC., Coptis chinensis Franch., Leonurus japonicus Houtt., Lycopus lucidus Turcz. var. hirtus Regel, Atractylodes lancea (DC) Koidz., Citrus aurantium L., Gypsum Fibrosum, Cinnamomum cassia Presl., Glycyrrhiza uralensis Fisch. Studies have shown that Lycii Folium and Coptidis Rhizome have demonstrated efficacy in improving insulin resistance, regulating abnormalities in lipid metabolism, and preventing obesity (Yang et al., 2024; Zhao et al., 2020). Glycyrrhizae radix et rhizome extract exhibited anti-androgen and estrogen-like activity and has been used in the treatment of PCOS(Minnetti et al., 2022; Sabbadin et al., 2019). Furthermore, clinical trials have shown that cinnamon supplementation benefits the menstrual cycle and reduces insulin resistance in PCOS patients (Hajimonfarednejad et al., 2018).

In this study, we first determined the clinical efficacy and characteristics of TJZL in treating PCOS through a multicenter single-arm clinical trial. Additionally, we established PCOS rat and mouse models by combining letrozole with high-fat feeding, and further confirmed the effectiveness of TJZL in treating PCOS from histopathological and fertility perspectives. Subsequently, the regulatory characteristics of the metabolic and transcriptional profiles of PCOS after treatment with Tianjing Zelian were investigated. The key targets and pathways were validated by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry in PCOS mice. Finally, molecular docking analysis was employed to explore the potential active ingredients of TJZL in the treatment of PCOS. Our research aims to reveal the clinical characteristics and mechanisms of TJZL in treating PCOS.