{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T20:03:38Z","timestamp":1769285018092,"version":"3.49.0"},"reference-count":36,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Development Program Project of Jilin Province","award":["YDZJ202501ZYTS199"],"award-info":[{"award-number":["YDZJ202501ZYTS199"]}]},{"name":"Science and Technology Research Project of the Department of Education of Jilin Province","award":["JJKH20241088KJ"],"award-info":[{"award-number":["JJKH20241088KJ"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Tendinopathy remains a prevalent musculoskeletal disorder with limited disease-modifying pharmacotherapy. This study aimed to identify a reparative agent from the traditional medicinal herb Eucommiae Cortex and elucidate its mechanism of action. Methods: A bioactive fraction was first identified through a bioactivity-guided strategy using tenocyte cytoprotection and migration assays, then characterized by UHPLC-HRMS\/MS. Its major constituent, aucubin (AU), which mirrors the fraction\u2019s key pharmacological activities, was evaluated both in vitro and in vivo. In H2O2-injured tenocytes, AU\u2019s effects on viability, apoptosis, oxidative stress (ROS, MDA, SOD) and inflammation (IL-1\u03b2, TNF-\u03b1) were assessed, with specific focus on estrogen receptor (ER) pathway involvement using pharmacological tools (17\u03b2-estradiol and (R, R)-THC). In a collagenase-induced Achilles tendinopathy model using male SD rats, AU\u2019s therapeutic efficacy was evaluated via multimodal assessment: ultrasonography, histopathology (H&amp;E, Masson\u2019s trichrome, Sirius red), TEM, immunohistochemistry, and biochemical analysis of tissue markers. Results: AU effectively attenuated H2O2-induced tenocyte injury by enhancing viability, reducing apoptosis, and mitigating oxidative\/inflammatory stress. These effects were mimicked by 17\u03b2-estradiol and reversed by the selective ER\u03b2 antagonist (R, R)-THC, indicating ER\u03b2 dependence. In vivo, AU treatment promoted structural and functional recovery, improved collagen maturity (increased Col I\/Col III ratio and fibril diameter), suppressed matrix degradation (MMP-3, MMP-13) and apoptosis, and reduced oxidative stress and inflammation in tendon tissue. Conclusions: This study identifies aucubin as a novel phytoestrogenic compound from Eucommiae Cortex that promotes tendon repair through an ER\u03b2-mediated mechanism. These findings position ER\u03b2 activation as a promising therapeutic strategy for tendinopathy and highlight AU as a promising lead compound for further development.<\/jats:p>","DOI":"10.3390\/ph19020194","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T10:41:34Z","timestamp":1769164894000},"page":"194","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aucubin from Eucommiae Cortex Alleviates Tendinopathy via an Estrogen Receptor \u03b2-Mediated Mechanism"],"prefix":"10.3390","volume":"19","author":[{"given":"Guorong","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuang","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keyi","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meiqi","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8408-936X","authenticated-orcid":false,"given":"Qiang","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jialin","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Luan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Qiu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhidong","family":"Qiu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41572-020-00234-1","article-title":"Tendinopathy","volume":"7","author":"Millar","year":"2021","journal-title":"Nat. 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