{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:55:03Z","timestamp":1793382903185,"version":"4.5.0"},"reference-count":100,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Escin, a natural medicinal saponin, has garnered significant attention in recent years for its pharmacological effects in various diseases. Though the structure and pharmacodynamic targets of escin are documented, reviews on its efficacy and mechanisms were still mainly from the clinical application perspective at the organ level or animal models. Deeper discussion at the tissue microenvironment level remains sparse, as the sophisticated cell and molecular technique is required. Contradictory conclusion might occur if such experiment setups are not carefully distinguished. This article reviews and analyzes literature to discuss escin\u2019s ability to improve the tissue microenvironment of blood vessel walls and elucidates the underlying mechanisms. Escin demonstrates significant anti-inflammatory properties and neutralizes free radicals, thereby protecting vascular endothelial cells from oxidative stress. Additionally, escin\u2019s anticoagulant properties reduce blood viscosity, preventing clot formation and maintaining vessel patency. These mechanisms collectively enhance the tissue microenvironment of blood vessel walls and promote cardiovascular health, which provides a multi-target therapeutic strategy for cardiovascular diseases (CVD), integrating anti-inflammatory, antioxidant, endothelial repair, and microcirulation-enhancing mechanisms, consistent with current pathophysiological insights. The article also addresses the current research status, challenges, and future potential of escin in vascular protection, offering new perspectives and strategies for CVD treatment and prevention.<\/jats:p>","DOI":"10.1515\/biol-2025-1167","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T06:55:51Z","timestamp":1762930551000},"source":"Crossref","is-referenced-by-count":4,"title":["Efficacy and mechanism of escin in improving the tissue microenvironment of blood vessel walls via anti-inflammatory and anticoagulant effects: Implications for clinical practice"],"prefix":"10.1515","volume":"20","author":[{"given":"Linyin","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Chemical and Materials Engineering, Hainan Vocational University of Science and Technology , Haikou , Hainan, 57010 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemical and Materials Engineering, Hainan Vocational University of Science and Technology , Haikou , Hainan, 57010 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Chemical and Materials Engineering, Hainan Vocational University of Science and Technology , Haikou , Hainan, 57010 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Decai","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Chemical and Materials Engineering, Hainan Vocational University of Science and Technology , Haikou , Hainan, 57010 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of NBC Protection for Civilian, Research Institute of Chemical Defense, Academy of Military Science , Beijing , 102205 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Chen","sequence":"additional","affiliation":[{"name":"Economic and Technological Development Zone, Yantai Haisen Big Data Co., Ltd , No. 48, Nanchang Street , Yantai , Shandong, 265500 , People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xiao","sequence":"additional","affiliation":[{"name":"Wuhan Aimin Pharmaceutical Co., LTD , Wuhan , Hubei , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"2025122123392397421_j_biol-2025-1167_ref_001","doi-asserted-by":"crossref","unstructured":"Idris S, Mishra A, Khushtar M. Phytochemical, ethanomedicinal and pharmacological applications of escin from Aesculus hippocastanum L. towards future medicine. J Basic Clin Physiol Pharmacol. 2020;31(5):20190115.","DOI":"10.1515\/jbcpp-2019-0115"},{"key":"2025122123392397421_j_biol-2025-1167_ref_002","doi-asserted-by":"crossref","unstructured":"Gallelli L. Escin: a review of its anti-edematous, antiinflammatory, and venotonic properties. Drug Des Dev Ther. 2019;13:3425\u201337.","DOI":"10.2147\/DDDT.S207720"},{"key":"2025122123392397421_j_biol-2025-1167_ref_003","doi-asserted-by":"crossref","unstructured":"Yang Y, Wang L, Yuan M, Yu Q, Fu F. Anti-inflammatory and gastroprotective effects of escin. Nat Prod Commun. 2020;15(12):1934578X20982111.","DOI":"10.1177\/1934578X20982111"},{"key":"2025122123392397421_j_biol-2025-1167_ref_004","doi-asserted-by":"crossref","unstructured":"Dudek-Makuch M, Studzi\u0144ska-Sroka E. Horse chestnut \u2013 efficacy and safety in chronic venous insufficiency: an overview. 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Escin inhibits angiogenesis by suppressing interleukin-8 and vascular endothelial growth factor production by blocking nuclear factor-\u03baB activation in pancreatic cancer cell lines. Oncol Rep. 2021;45(5):55.","DOI":"10.3892\/or.2021.8006"},{"key":"2025122123392397421_j_biol-2025-1167_ref_011","doi-asserted-by":"crossref","unstructured":"Varinsk\u00e1 L, F\u00e1ber L, Kello M, Petrovov\u00e1 E, Bal\u00e1\u017eov\u00e1 L, Sol\u00e1r P, et al. \u03b2-escin effectively modulates HUVECs proliferation and tube formation. Molecules. 2018;23(1):197.","DOI":"10.3390\/molecules23010197"},{"key":"2025122123392397421_j_biol-2025-1167_ref_012","doi-asserted-by":"crossref","unstructured":"Kwak HS, An H, Alam MB, Choi WS, Lee SY, Lee SH. Inhibition of migration and invasion in melanoma cells by \u03b2-escin via the ERK\/NF-\u03baB signaling pathway. 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