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Its action in hypoxic pulmonary hypertension (HPH) remains poorly understood. We evaluated the potential of ST on HPH and its molecular mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      ST was evaluated on a rat model HPH. Single\u2010cell RNA sequencing (scRNA\u2010seq) identified ST\u2010modulated cell clusters. ST regulation on endothelial dysfunction\u2010induced neutrophil migration\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      was studied. Molecular docking, cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) analysis were used to identify targets of ST. The molecular mechanism by which ST modulates endothelial cell dysfunction through gene silencing experiments was also investigated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      ST significantly reduced pulmonary arterial pressure in HPH rats and alleviated pathological changes in lung tissue. scRNA\u2010seq showed that ST markedly decreased the proportion of neutrophils, down\u2010regulated the expression of their cell migration\u2010related genes and the gene expression of chemokines in endothelial cells.\n                      <jats:italic>In vivo<\/jats:italic>\n                      experimental indicated that ST reduced neutrophil infiltration in lung tissue and lowered inflammatory cytokine levels in bronchoalveolar lavage fluid. Further\n                      <jats:italic>in vitro<\/jats:italic>\n                      studies indicated that ST reduced neutrophil migration by inhibiting hypoxia\u2010induced endothelial dysfunction. ST inhibited P65 phosphorylation\u2010mediated endothelial dysfunction by targeting chloride intracellular channel 4 (CLIC4). Inhibiting CLIC4 activation through blocking the cascade reaction of CLIC4 up\u2010regulation and activation induced by pro\u2010inflammatory cytokines. Silencing endothelial cell CLIC4 abolishes ST inhibitory effects on inflammatory cytokine expression and regulatory impact on P65 activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>ST targeted CLIC4 inhibits NF\u2010\u03baB p65 activation would have therapeutic effects against HPH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70676","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:52:27Z","timestamp":1790837547000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sinapine thiocyanate (ST) ameliorates endothelial cell dysfunction by targeting chloride intracellular channel 4 (CLIC4) to treat hypoxia\u2010induced pulmonary 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