{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:46:25Z","timestamp":1791945985460,"version":"4.3.4"},"reference-count":59,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012154","name":"Graduate Research and Innovation Projects of Jiangsu Province","doi-asserted-by":"publisher","award":["KYCX24_1030"],"award-info":[{"award-number":["KYCX24_1030"]}],"id":[{"id":"10.13039\/501100012154","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82574655"],"award-info":[{"award-number":["82574655"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Non\u2010muscle myosin heavy chain IIA (NMMHC IIA) has emerged as a significant therapeutic target in vascular diseases and sepsis. However, effective interventions targeting NMMHC IIA in sepsis\u2010induced endothelial dysfunction remain unelucidated. Here, we have assessed ginsenoside Ra1 (Ra1) as a potent NMMHC IIA inhibitor and evaluate its efficacy and underlying mechanisms in sepsis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>We used the caecal ligation and puncture model of polymicrobial sepsis in mice. Survival rate, body temperature, pathological changes, vascular permeability and plasma biochemical indicators were measured to evaluate the effects of Ra1 treatment. Molecular docking technique, cellular thermal shift assay, microscale thermophoresis assay and surface plasmon resonance were performed to confirm the binding of Ra1 with NMMHC IIA. Downstream genes affected by Ra1 were screened via RNA\u2010sequencing and validated using western blotting and immunofluorescence. In vitro, a lipopolysaccharide\u2010induced endothelial barrier injury model in human umbilical vein endothelial cells was established, and endothelial permeability was evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Ra1 bound strongly to NMMHC IIA, whose knockdown ameliorated sepsis\u2010induced endothelial barrier disruption and multi\u2010organ injury (lung, intestine, liver and kidney). Ra1 attenuated mortality, hypothermia, multi\u2010organ injury, vascular hyperpermeability and endothelial junction disruption in septic mice. Mechanistically, Ra1 inhibited TLR4\/NF\u2010\u03baB\/NLRP3 signalling to exert its protective effects, which were absent after NMMHC IIA was silenced, demonstrating an NMMHC IIA\u2013dependent mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Our findings identify Ra1 as a potential inhibitor of NMMHC IIA and provide mechanistic insight into therapeutic strategies targeting endothelial dysfunction in sepsis, which warrants further investigation in clinical studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70689","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:34:53Z","timestamp":1791945293000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ginsenoside Ra1 alleviates endothelial barrier dysfunction and 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