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We also used fluorescence microscopy, RT\u2010qPCR, molecular docking and X\u2010ray crystallography.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      CHAL13\u2010induced vasorelaxation was unaffected by endothelial removal or inhibition of the eNOS\u2013NO\u2013sGC\u2013cGMP signalling pathway in SHR. CHAL13 reduced extracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx in Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \u2010free medium and decreased KCl\u2010induced intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      increases in primary vascular smooth muscle cells (pVSMCs). CHAL13 also suppressed the contraction induced by the Ca\n                      <jats:sub>V<\/jats:sub>\n                      1.2 agonist Bay\u2010K8644 in SHR aortic rings, supporting a direct inhibitory effect on vascular Ca\n                      <jats:sub>V<\/jats:sub>\n                      1.2 channels. Notably, activation of K\n                      <jats:sub>Ca<\/jats:sub>\n                      , K\n                      <jats:sub>V<\/jats:sub>\n                      and K\n                      <jats:sub>ATP<\/jats:sub>\n                      channels contributed significantly to CHAL13's vasorelaxant effect. Compared with its precursor metabolite, CHAL13 exhibited stronger interactions with the pore\u2010forming \u03b1\n                      <jats:sub>1C<\/jats:sub>\n                      subunit of the Ca\n                      <jats:sub>V<\/jats:sub>\n                      1.2 channel, near the binding site of voltage\u2010gated calcium channel blockers, and with the \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      subunit of the K\n                      <jats:sub>Ca<\/jats:sub>\n                      1.1 channel, near the binding site of known channel activators. CHAL13 also showed predicted interactions with K\n                      <jats:sub>V<\/jats:sub>\n                      1.2 and vascular K\n                      <jats:sub>ATP<\/jats:sub>\n                      channels. Aortic tissues treated with CHAL13 showed upregulated expression of\n                      <jats:italic>Kcnmb1<\/jats:italic>\n                      and\n                      <jats:italic>Kcna5<\/jats:italic>\n                      transcripts, which are associated with vascular relaxation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>\n                      CHAL13 exerts a vasorelaxant effect primarily through Ca\n                      <jats:sub>V<\/jats:sub>\n                      1.2 channel blockade and coordinated activation of multiple K\n                      <jats:sup>+<\/jats:sup>\n                      channel subtypes, suggesting membrane hyperpolarization in vascular smooth muscle. Its favourable chemical, pharmacokinetic and toxicological profiles support its potential as a novel antihypertensive scaffold.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70497","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T23:19:08Z","timestamp":1778800748000},"page":"4899-4918","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacological and molecular characterization of a chalcone analogue derived from a\n                    <i>Senecio nutans<\/i>\n                    metabolite: Modulation of Ca\n                    <sub>V<\/sub>\n                    1.2 and K\n                    <sub>Ca<\/sub>\n                    1.1 channels in hypertensive 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