Mechanisms of Action of Zishen Yutai pills in Treating Premature Ovarian Failure Determined by Integrating UHPLC-Q-TOF-MS and Network Pharmacology Analysis [post]

Lei Dang, Chunbo Zhang, Biru Su, Ning Na, Qiuling Huang, Su Zhou, Meng Wu, Wenqing Ma, Man Wang, Pengfei Cui, Yan Li, Shixuan Wang
2022 unpublished
Background: Zishen Yutai (ZSYT) pill, a patent Chinese medicine, has been widely used in the treatment of infertility, abortion, and adjunctive treatment of in vitro fertilization (IVF) for decades. Recently, the results of clinical observations showed that premature ovarian failure (POF) patients exhibited improved expression of steroids and clinical symptoms associated with hormone disorders after treatment with ZSYT pills. However, the pharmacological mechanism of action of these pills
more » ... s unclear.Methods: The components of ZSYT found in blood circulation were identified via ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) technique in the serum of POF mice after oral administration of ZSYT pills. The potential targets of components were screened using Traditional Chinese Medicine Systems Pharmacology Database, Traditional Chinese Medicine Database@Taiwan, Drugbank Database, PubChem, HIT, Pharmapper, and SwissTargetPrediction. The target genes associated with POF were collected from Online Mendelian Inheritance in Man Database, PharmGkb, Genecards, therapeutic target database, and Genetic Association Database. The overlapping genes between the potential targets of ZSYT components and the target genes associated with POF were clarified via protein-protein interaction (PPI), pathway, and network analysis.Results: Nineteen components in ZSYT pills were detected in the serum of POF mice after oral administration. A total of 695 ZSYT-related targets was screened, and 344 POF-related targets were collected. From the results of ZSYT-POF PPI analysis, CYP19A1, AKR1C3, ESR1, AR, and SRD5A2 were identified as key targets via network analysis, indicating their core role in the treatment of POF with ZSYT pills. Moreover, the pathway enrichment results suggested that ZSYT pills treat POF primarily by regulating neuroactive ligand-receptor interaction, steroid hormone biosynthesis, and ovarian steroidogenesis.Conclusions: We demonstrated that regulation of neuroactive ligand-receptor interaction, steroid hormone biosynthesis, and ovarian steroidogenesis are very likely to be therapeutic mechanism of ZSYT pills in treating POF. Our study suggests that combining the analysis of ZSYT pills components in blood in vivo in the POF models and network pharmacology prediction may offer a tool to characterize the mechanism of ZSYT pills in the POF.
doi:10.21203/rs.3.rs-1176592/v1 fatcat:2tmrekxmprbczfkaeewcwdifry