{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:37Z","timestamp":1787027857415,"version":"build-2736575974"},"reference-count":128,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural science foundation project of Sichuan","award":["2024NSFSC0599"],"award-info":[{"award-number":["2024NSFSC0599"]}]},{"name":"Key Research and Development Program of Chengdu","award":["2023-YF09-00052-SN"],"award-info":[{"award-number":["2023-YF09-00052-SN"]}]},{"name":"Young Teachers\u2019 Science and Technology Innovation Capability Enhancement Project of Sichuan University","award":["2024SCUQJTX037"],"award-info":[{"award-number":["2024SCUQJTX037"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81970738"],"award-info":[{"award-number":["81970738"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>The immune system is a pivotal regulator of reproductive physiology, maintaining tissue homeostasis essential for successful pregnancy while contributing to infertility and reproductive disorders when dysregulated. Natural products represent a valuable source of novel immunomodulatory agents. Icariin (ICA), a prenylated flavonoid glycoside isolated from Epimedium species (Horny Goat Weed), has a long-standing traditional use for \u201cinvigorating yang,\u201d which modern research attributes to its reproductive function-enhancing properties. This review synthesizes emerging evidence that the beneficial effects of ICA on female and male reproductive health are primarily mediated through its sophisticated immunomodulatory actions on the reproductive\u2013immune axis. We systematically dissect the molecular mechanisms by which ICA reprograms the reproductive immune microenvironment, focusing on its regulation of macrophage polarization, T-helper cell (Th1\/Th2\/Th17) and regulatory T-cell (Treg) balance, and suppression of key pro-inflammatory signaling pathways (NF-\u03baB, NLRP3 inflammasome, JAK-STAT) in ovarian, uterine, and testicular tissues. This review provides a detailed account of how ICA modulates reproductive disorders via regulating immune responses, with the aim of offering innovative strategies for the design of novel immunomodulatory therapies targeting reproductive diseases.<\/jats:p>","DOI":"10.3390\/cimb48040366","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T10:09:21Z","timestamp":1775038161000},"page":"366","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Icariin Modulates the Reproductive-Immune Axis: Molecular Insights and Therapeutic Potential"],"prefix":"10.3390","volume":"48","author":[{"given":"Rongyu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Traditional Chinese Medicine, West China Second University Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University Ministry of Education, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University Ministry of Education, Chengdu 610041, China"},{"name":"Reproductive Endocrinology and Regulation Laboratory, West China Second University Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinwen","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, West China Second University Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University Ministry of Education, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lirong","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, West China Second University Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University Ministry of Education, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University Ministry of Education, Chengdu 610041, China"},{"name":"National Center for Birth Defect Monitoring, West China Second University Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/jog.14135","article-title":"Endometrial stromal cells treated by tumor necrosis factor-\u03b1 stimulate macrophages polarized toward M2 via interleukin-6 and monocyte chemoattractant protein-1","volume":"46","author":"Li","year":"2020","journal-title":"J. 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