Molecular Targets and Associated Signaling Pathways of Jingshu Granules in Ovarian Cysts Based on Systemic Pharmacological Analysis

Abstract

Background. 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. Methods. 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. Results. 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. Conclusion. 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.

Risk factors and pharmacotherapy for chemotherapy-induced peripheral neuropathy in paclitaxel-treated female cancer survivors: A retrospective study in Japan

“…This was a single-center, retrospective cohort study using data obtained from electronic medical records of female patients who were diagnosed with breast cancer or gynecologic (ovarian, fallopian tube or endometrial) cancer and underwent paclitaxel-based chemotherapy at Kindai University Hospital in Osakasayama City, Japan, between 1 st January, 2016, and 31 st December, 2019. The collected patient information included age, body surface area (BSA), body mass index (BMI), metastasis at initial diagnosis, treatment history, ongoing diseases, such as diabetes, hyperlipidemia and hypertension, medical history of non-cancer, female hormone-related diseases (defined as diseases the pathogenesis of which involves altered levels of estrogens) including ovarian cyst, uterine fibroid and endometriosis, typical diseases associated with estrogens [25][26][27]. Information concerning the diagnosis of PIPN was also collected retrospectively from the medical record.…”

The mechanism of ginger and its processed products in the treatment of estradiol valerate coupled with oxytocin-induced dysmenorrhea in mice via regulating the TRP ion channel-mediated ERK1/2/NF-κB signaling pathway

“…8 TRPV1 and TRPM8 channel proteins play important roles in the onset and development of PD. 9,10 The TRPV1 channel protein is involved in the pathology of post-inflammatory hyperalgesia in PD after activation by multiple ligand-like substances, inflammatory mediators (such as arachidonic acid metabolites), and tissue injury stimuli. 11,12 The TRPM8 channel protein can be activated by cold temperatures (<28 °C) or in response to pain, to induce a cation influx (including Ca 2+ ), affecting the initiation of PD.…”