{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T10:27:31Z","timestamp":1786616851725,"version":"build-2736575974"},"reference-count":31,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The effect of Corosolic acid (CA) on vascular tone and the possible mecha-nisms involved remain unclear. The SPF-grade male Sprague-Dawley rats (Animal Ethics Approval ID: USM\/IACUC\/2025\/(155)(1406)) were used. The vasorelaxant effects of CA were evaluated in endothelium-intact and endothelium-denuded rings precontracted with phenylephrine (PE), and in endothelium-intact rings precontracted with KCl. Possible mechanisms were examined using L-NAME, ODQ, methylene blue, indomethacin, atropine, propranolol, and potassium channel blockers (glibenclamide, TEA, BaCl2, and 4-AP). The effects of CA on voltage-operated calcium channels (VOCCs) and IP3 receptor (IP3R)-mediated sarcoplasmic reticulum calcium release were also assessed. CA concentration-dependently relaxed endothelium-intact aortic rings precontracted with PE (RMAX = 90.08 \u00b1 7.33%; pD2 = 4.21 \u00b1 0.08). The relaxation response was markedly reduced after endothelial removal and in KCl-precontracted rings. EDRF pathway inhibitors (L-NAME, ODQ, methylene blue, and indomethacin) and GPCR-related antagonists (atropine and propranolol) attenuated CA-induced relaxation. Among potassium channel blockers, glibenclamide and TEA showed stronger inhibitory effects. CA did not significantly inhibit VOCC-mediated CaCl2-induced contraction but partially reduced PE-induced contraction under calcium-free conditions. The mechanisms for CA treating hypertension may involve NO\/cGMP signalling, COX-related prostanoid pathways, GPCR-related mechanisms, potassium channel modulation, and partial inhibition of IP3R-mediated calcium release.<\/jats:p>","DOI":"10.3390\/molecules31162822","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T09:31:09Z","timestamp":1786613469000},"page":"2822","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Corosolic Acid Induces Endothelium-Dependent Vasorelaxation in Isolated Rat Aortic Rings"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3134-6779","authenticated-orcid":false,"given":"Fangying","family":"Chen","sequence":"first","affiliation":[{"name":"Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Gelugor 11800, Pulau Pinang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7259-4010","authenticated-orcid":false,"given":"Wan Yin","family":"Tew","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia (USM), Gelugor 11800, Pulau Pinang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6639-9718","authenticated-orcid":false,"given":"Ming Thong","family":"Ong","sequence":"additional","affiliation":[{"name":"Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Gelugor 11800, Pulau Pinang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4138-711X","authenticated-orcid":false,"given":"Mun Fei","family":"Yam","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia (USM), Gelugor 11800, Pulau Pinang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"175057","DOI":"10.1016\/j.ejphar.2022.175057","article-title":"New paeonol derivative C302 reduces hypertension in spontaneously hypertensive rats through endothelium-dependent and endothelium-independent vasodilation","volume":"927","author":"Li","year":"2022","journal-title":"Eur. 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