College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan City, Shandong Province, 250355, China.
Biomed Res Int. 2021 Jan 21;2021:6660087. doi: 10.1155/2021/6660087. eCollection 2021.
More than a third of women could develop ovarian cysts during their lifetime. Jingshu granules are used for the treatment of gynecological disease of primary dysmenorrhea. However, the molecular mechanisms of Jingshu granules in ovarian cysts are still unreported. We aimed to find the active ingredients, molecular targets, and potential signaling pathways of Jingshu granules in ovarian cysts by using the systemic pharmacological analysis.
Firstly, the effect of Jingshu granules on female hormones and reproductive organs of young female rats was evaluated. Secondly, candidate pharmaceutical ingredients of Jingshu granules were retrieved from the traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform. Potential protein targets for the active ingredients in Jingshu granules were then identified according to the oral bioavailability and drug-likeness indices. Thirdly, ovarian cyst-related gene targets were screened based on different databases. Finally, enrichment analysis was used to analyze the potential biological function of intersection targets between Jingshu granules and ovarian cysts.
In young female rats, Jingshu granules reduced the secretion of estradiol, progesterone, and prolactin and could affect the development of the uterus. This suggested that Jingshu granules played roles in hormone secretion and reproduction. From the TCMSP, a total of 1021 pharmaceutical ingredients of Jingshu granules were retrieved. After further screening, a total of 166 active ingredients and 159 protein targets of Jingshu granules were identified. In addition, 4488 gene targets of ovarian cysts were screened out. After taking the intersection, a total of 110 intersection targets were identified between potential protein targets of Jingshu granules and gene targets of ovarian cysts. In the functional analysis of 110 intersection targets, 8 signaling pathways including progesterone-mediated oocyte maturation (MAPK8 and CDK1 involved), GnRH signaling pathway (JUN involved), T cell receptor signaling pathway and Toll-like receptor signaling pathway (MAPK1 involved), NOD-like receptor signaling pathway (TNF, IL6, and IL1B involved), p53 signaling pathway (CDK2 and CDK4 involved), VEGF signaling pathway (MAPK14 involved), and PPAR signaling pathway (PPARG involved) were obtained.
Our study revealed that Jingshu granules could function in patients with ovarian cysts through a number of molecular targets and signaling pathways. Our study may provide a new field into the mechanisms of Jingshu granules in ovarian cysts, from the molecular to the signaling pathway level.
超过三分之一的女性在其一生中可能会患上卵巢囊肿。经舒颗粒用于治疗原发性痛经的妇科疾病。然而，经舒颗粒治疗卵巢囊肿的分子机制仍未见报道。我们旨在通过系统药理学分析寻找经舒颗粒治疗卵巢囊肿的活性成分、分子靶标和潜在信号通路。
首先，评估经舒颗粒对年轻雌性大鼠的激素和生殖器官的影响。其次，从中药系统药理学（TCMSP）数据库和分析平台中检索经舒颗粒的候选药物成分。然后根据口服生物利用度和药物样指数确定经舒颗粒中活性成分的潜在蛋白靶点。再次，基于不同数据库筛选卵巢囊肿相关基因靶点。最后，采用富集分析方法分析经舒颗粒与卵巢囊肿的交集靶点的潜在生物学功能。
在年轻雌性大鼠中，经舒颗粒降低了雌二醇、孕酮和催乳素的分泌，并且可能影响子宫的发育。这表明经舒颗粒在激素分泌和生殖方面发挥作用。从 TCMSP 中总共检索到 1021 种经舒颗粒的药物成分。经过进一步筛选，共鉴定出 166 种经舒颗粒的活性成分和 159 个经舒颗粒的蛋白靶点。此外，筛选出 4488 个卵巢囊肿的基因靶点。取交集后，共鉴定出经舒颗粒潜在蛋白靶点与卵巢囊肿基因靶点之间的 110 个交集靶点。在 110 个交集靶点的功能分析中，共获得了包括孕激素介导的卵母细胞成熟（涉及 MAPK8 和 CDK1）、促性腺激素释放激素信号通路（涉及 JUN）、T 细胞受体信号通路和 Toll 样受体信号通路（涉及 MAPK1）、NOD 样受体信号通路（涉及 TNF、IL6 和 IL1B）、p53 信号通路（涉及 CDK2 和 CDK4）、VEGF 信号通路（涉及 MAPK14）和过氧化物酶体增殖物激活受体信号通路（涉及 PPARG）在内的 8 条信号通路。
本研究表明，经舒颗粒可通过多种分子靶标和信号通路作用于卵巢囊肿患者。我们的研究可能为经舒颗粒治疗卵巢囊肿的机制提供一个从分子到信号通路水平的新领域。
