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Regulation of calcium homeostasis in vascular smooth muscle cells (VSMC) is viewed as one of the main mechanisms for controlling blood pressure. L\u2010type voltage\u2010gated calcium channel (VGCC) blockers are commonly used for controlling hypertension. Recently, the transient receptor potential canonical (TRPC) channels were found in blood vessels of different animal species with evidence of their roles in the regulation of vascular contractility. In this study, we studied the mechanism of actions of schwarzinicine A focusing on its regulation of L\u2010type VGCC and TRPC channels. Schwarzinicine A exhibited the highest vasorelaxant effect (123.1%) compared to other calcium channel blockers. It also overtly attenuated calcium\u2010induced contractions of the rat isolated aortae in a calcium\u2010free environment showing its mechanism to inhibit calcium influx. Fluorometric intracellular calcium recordings confirmed its inhibition of hTRPC3\u2010, hTRPC4\u2010, hTRPC5\u2010 and hTRPC6\u2010mediated calcium influx into HEK cells with IC<jats:sub>50<\/jats:sub> values of 3, 17, 19 and 7\u00a0\u03bcM, respectively. The evidence gathered in this study suggests that schwarzinicine A blocks multiple TRPC channels and L\u2010type VGCC to exert a significant vascular relaxation response.<\/jats:p>","DOI":"10.1002\/ptr.7489","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T23:30:15Z","timestamp":1652225415000},"page":"2952-2963","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Schwarzinicine A inhibits transient receptor potential canonical channels and exhibits overt vasorelaxation effects"],"prefix":"10.1002","volume":"36","author":[{"given":"Yin\u2010Ying","family":"Mak","sequence":"first","affiliation":[{"name":"School of Pharmacy University of Nottingham Malaysia  Semenyih Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bi\u2010Juin","family":"Loong","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Nottingham Malaysia  Semenyih 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