文献类型：期刊文献

英文题名：Potential mechanism prediction of indole-3-propionic acid against diminished ovarian reserve via network pharmacology, molecular docking and experimental verification

作者：Liu, Ahui[1,2];Liu, Zhijun[4];Shen, Haofei[1,2,3];Du, Wenjing[1,2,3];Jiang, Yanbiao[1,2];Wang, Liyan[2,3];Zhang, Rui[2,3];Jin, Panpan[2,3];Zhang, Xuehong[2,3]

第一作者：Liu, Ahui

通信作者：Jin, PP[1];Zhang, XH[1];Jin, PP[2];Zhang, XH[2]

机构：[1]Lanzhou Univ, Sch Clin Med 1, Lanzhou, Gansu, Peoples R China;[2]Lanzhou Univ, Hosp 1, Reprod Med Ctr, 1 Dong Gang Xi Rd, Lanzhou 730000, Gansu, Peoples R China;[3]Key Lab Reprod Med & Embryo, Lanzhou, Gansu, Peoples R China;[4]Gansu Univ Chinese Med, Affiliated Hosp, Lanzhou, Gansu, Peoples R China

第一机构：Lanzhou Univ, Sch Clin Med 1, Lanzhou, Gansu, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Hosp 1, Reprod Med Ctr, 1 Dong Gang Xi Rd, Lanzhou 730000, Gansu, Peoples R China;[2]corresponding author), Key Lab Reprod Med & Embryo, Lanzhou, Gansu, Peoples R China.

年份：2024

卷号：24

期号：1

外文期刊名：BMC COMPLEMENTARY MEDICINE AND THERAPIES

收录：;Scopus(收录号：2-s2.0-85202178682);WOS:【SCI-EXPANDED(收录号:WOS:001300029400002)】；

基金：This study was supported by grants from the National Natural Science Foundation of China (81960273); Lanzhou Youth Science and Technology Talent Innovation Project (2023-4-47); Lanzhou Chengguan District Science and Technology Plan Project (2023-11-3); Natural Science Foundation of Gansu Province (23JRRA1603); and Hospital Fund of the First Hospital of Lanzhou University (ldyyyn2022-20).

语种：英文

外文关键词：Indole-3-propionic acid; Diminished ovarian reserve; Network pharmacology; Molecular docking; Molecular dynamics simulation; Experimental verification

摘要：BackgroundOxidative stress (OS) is one of the major causes of ovarian aging and dysfunction. Indole-3-propionic acid (IPA) is an indole compound derived from tryptophan with free radical scavenging and antioxidant properties, and thus may have potential applications in protecting ovarian function, although the exact mechanisms are unknown. This study aims to preliminarily elucidate the potential mechanisms of IPA that benefit ovarian reserve function through network pharmacology, molecular docking, and experimental verification.MethodsThe related protein targets of IPA were searched on SwissTargetPrediction, TargetNet, BATMAN-TCM, and PharmMapper databases. The potential targets of diminished ovarian reserve (DOR) were identified from OMIM, GeneCards, DrugBank, and DisGeNET databases. The common targets were uploaded directly to the STRING database to construct PPI networks. We then performed GO and KEGG enrichment analysis on the targets. Subsequently, molecular docking and molecular dynamics simulation were used to validate the binding conformation of IPA to candidate targets. Furthermore, we carried out in vitro experiments to validate the prediction results of network pharmacology.ResultsWe identified a total of 61 potential targets for the interaction of IPA with DOR. The PPI network topological parameter analysis yielded 13 hub genes for DOR treatment. The GO biological process enrichment analysis identified 293 entries, mainly enriched in aging, signal transduction, response to hypoxia, negative regulation of apoptotic process, and positive regulation of cell proliferation. The KEGG enrichment analysis mainly included lipid and atherosclerosis, progesterone-mediated oocyte maturation, AGE-RAGE, relaxin, estrogen, and other signaling pathways. The molecular docking further revealed the direct binding of IPA with six hub proteins including NOS3, AKT1, EGFR, PPARA, SRC, and TNF. In vitro experiments showed that IPA pretreatment attenuated H2O2-induced cellular oxidative stress damage, while IPA exerted cytoprotective and antioxidant damage effects by regulating the six hub genes and antioxidant proteins.ConclusionWe systematically illustrated the potential protective effects of IPA against DOR through multiple targets and pathways using network pharmacology, and further verified the cytoprotective effect and antioxidant properties of IPA through in vitro experiments. These findings provide new insights into the targets and molecular mechanisms whereby IPA improves DOR.