{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:45:34Z","timestamp":1792061134210,"version":"4.4.0"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82460075"],"award-info":[{"award-number":["82460075"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004607","name":"Natural Science Foundation of Guangxi Province","doi-asserted-by":"publisher","award":["2025GXNSFAA069092"],"award-info":[{"award-number":["2025GXNSFAA069092"]}],"id":[{"id":"10.13039\/501100004607","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pulm. circ."],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pulmonary arterial hypertension (PAH) is a progressive and lethal disorder with limited therapeutic options. \u03b2\u2010sitosterol, a plant compound, has shown potential in managing PAH, but its protective mechanisms remain unclear. We evaluated the protective effects of \u03b2\u2010sitosterol against monocrotaline (MCT)\u2010induced PAH in rats and explored the underlying mechanisms. First, network pharmacology was used to predict potential targets of \u03b2\u2010sitosterol in PAH. A rat model of PAH was established by a single subcutaneous injection of MCT (60\u2009mg\/kg). From day 28 after MCT injection, PAH rats were treated with \u03b2\u2010sitosterol (100\u2009mg\/kg\/day) by gavage for 28 days. Histopathological analysis, RT\u2010qPCR, and Western blotting were performed to evaluate inflammatory infiltration, cellular proliferation, apoptosis, and the activity of the VEGF\/PI3K\/AKT pathway in lung tissues. Network pharmacology analysis identified the VEGF\/PI3K\/AKT pathway as centrally implicated.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , \u03b2\u2010sitosterol treatment significantly improved hemodynamic parameters and right ventricular function, reducing pulmonary vascular remodeling. Furthermore, \u03b2\u2010sitosterol suppressed vascular inflammation and proliferation while promoting apoptosis. RT\u2010qPCR analysis revealed that \u03b2\u2010sitosterol significantly reduced mRNA levels of VEGF,\n                    <jats:italic>TNF\u2010\u03b1, IL\u20106, IL\u20101\u03b2, Collagen I, and TGF\u2010\u03b21<\/jats:italic>\n                    compared with the MCT group. Western blotting demonstrated that \u03b2\u2010sitosterol decreased the phosphorylation of VEGFR2, PI3K and AKT, upregulated Bax expression, and downregulated PCNA and Bcl\u20102. In conclusion, \u03b2\u2010sitosterol may alleviate PAH with the involvement of the VEGF\/PI3K\/AKT signaling pathway. These findings suggest the therapeutic potential of \u03b2\u2010sitosterol against PAH and offer preliminary insights into its molecular mechanisms.\n                  <\/jats:p>","DOI":"10.1002\/pul2.70428","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:31:56Z","timestamp":1791901916000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b2\u2010sitosterol Alleviates Pulmonary Arterial Hypertension in Rats With Involvement of the VEGF\/PI3K\/AKT Signaling Pathway"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5734-9997","authenticated-orcid":false,"given":"Xiaobing","family":"Wu","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory of Precision Medicine in Cardio\u2010cerebrovascular Diseases Control and Prevention Guangxi Clinical Research Center for Cardio\u2010cerebrovascular Diseases Nanning 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