Chlorogenic acid exerts a senotherapeutic effect during endometrial decidualization via the mTOR/AKT signaling pathway in endometrial stromal cells

Chlorogenic acid exerts a senotherapeutic effect during endometrial decidualization via the mTOR/AKT signaling pathway in endometrial stromal cells | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 2 May 2025 V1 Latest version Share on Chlorogenic acid exerts a senotherapeutic effect during endometrial decidualization via the mTOR/AKT signaling pathway in endometrial stromal cells Authors : Woonghee Lee , Gwonhwa Song 0000-0003-2817-5323 , and Hyocheol Bae 0000-0002-9643-7797 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.174620738.89227254/v1 221 views 114 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background and Purpose Infertility due to age-related uterine dysfunction has become a significant global challenge. Cellular senescence and impaired decidualization in endometrial stromal cells (ESCs) are critical contributors to age-related fertility decline. Chlorogenic acid (CGA), a phenolic compound with proven anti-aging properties, has demonstrated potential therapeutic effects. However, its role in ESC senescence and decidualization remains unclear. Experimental Approach Network pharmacology and molecular docking approaches were employed to identify molecular targets of CGA and interactions among them. In vitro studies using senescent ESCs evaluated the effects CGA on cellular proliferation, senescence markers, mitochondrial biogenesis, and signaling pathways (mTOR/AKT/AMPK/SIRT1). Aged female mice were treated with CGA, and uterine tissues were analyzed histologically and molecularly to assess its anti-aging effects. Key Results CGA enhanced ESC proliferation, reduced senescence markers (P16, P21, SA-β-Gal), and promoted decidualization by increasing PRL, IGFBP1, and FOXO1 expression. CGA also restored mitochondrial biogenesis through the activation of SIRT1, AMPK, and PGC1α. Network pharmacology and docking studies identified mTOR and AKT as key targets, and CGA’s strong binding affinity to mTOR was supported by reduced mTOR phosphorylation in vitro and in vivo. In aged mice, CGA improved uterine morphology, reduced senescence markers, and partially restored reproductive parameters. Conclusions and Implications CGA alleviates senescence and enhances decidualization in ESCs via the mTOR/AKT signaling pathway. These findings suggest CGA as a promising senotherapeutic agent for addressing age-related infertility by improving uterine health and function. Supplementary Material File (british journal of pharmacology_thescs_cga_042125.docx) Download 187.86 KB File (table.docx) Download 24.55 KB File (table1.xlsx) Download 12.86 KB File (table2.xlsx) Download 12.81 KB Information & Authors Information Version history V1 Version 1 02 May 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords ageing/aging drug discovery/target validation reproduction pharmacology Authors Affiliations Woonghee Lee Korea University View all articles by this author Gwonhwa Song 0000-0003-2817-5323 Korea University View all articles by this author Hyocheol Bae 0000-0002-9643-7797 [email protected] Kyung Hee University - Global Campus View all articles by this author Metrics & Citations Metrics Article Usage 221 views 114 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Woonghee Lee, Gwonhwa Song, Hyocheol Bae. Chlorogenic acid exerts a senotherapeutic effect during endometrial decidualization via the mTOR/AKT signaling pathway in endometrial stromal cells. Authorea . 02 May 2025. DOI: https://doi.org/10.22541/au.174620738.89227254/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. 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