{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:06:43Z","timestamp":1792786003248,"version":"4.5.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Hubei Provincial Department of Education Middle-aged and Young Talent Project","award":["Q20182603"],"award-info":[{"award-number":["Q20182603"]}],"id":[{"id":"https:\/\/ror.org\/05yaa9j15","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Hypoxia-induced pulmonary hypertension (HPH) involves endothelial injury, vascular inflammation, and endothelial-mesenchymal transition (EndMT). Ginsenoside compound K (CK) has anti-inflammatory and vascular-protective properties, but its role in HPH remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Hypoxia-stimulated human pulmonary artery endothelial cells and chronic hypoxia-induced PH rats were used to assess the protective effects and mechanisms of CK.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>CK reduced MCP-1, BMP2, and RANKL expression, indicating attenuation of endothelial injury and pro-calcification responses. CK also dose-dependently reversed hypoxia-induced EndMT, shown by decreased vimentin and restored CD31 expression in vitro and in vivo. In HPH rats, intraperitoneal CK improved pulmonary hemodynamics, reduced right ventricular hypertrophy, and alleviated endothelial damage. Mechanistically, CK inhibited POSTN expression, downregulated TrkB, and suppressed recombinant POSTN-induced TGF-\u03b2\/Smad2\/3\/Snail signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CK protects against hypoxia-induced endothelial injury and vascular remodeling by inhibiting the POSTN-dependent EndMT pathway, suggesting its preventive potential for HPH-related cardiovascular complications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpp\/rgag125","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T16:19:53Z","timestamp":1792772393000},"source":"Crossref","is-referenced-by-count":0,"title":["Ginsenoside compound K attenuates hypoxic pulmonary hypertension endothelial injury by suppressing POSTN-TrkB-mediated endothelial-mesenchymal transition"],"prefix":"10.1093","volume":"78","author":[{"given":"Jiacai","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Pathology, Renmin Hospital of Wuhan University , Wuhan, Hubei 430060 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Wang","sequence":"additional","affiliation":[{"name":"Taikang Medical School, School of Basic Medical Sciences, Wuhan University , Wuhan, Hubei 430071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglin","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Pathology, Renmin Hospital of Wuhan University , Wuhan, Hubei 430060 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohang","family":"Fan","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Diseases, Xiang Yang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science , Xiangyang. Hubei 441053 ,","place":["China"]},{"name":"School of Basic Medicine, Hubei University of Arts and Science , Xiangyang, Hubei 441053 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3082-9548","authenticated-orcid":false,"given":"Rende","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture , No. 158 Wuyang Avenue, Enshi 445000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,23]]},"reference":[{"key":"2026102312194891500_ref1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI141467","article-title":"Endothelial FGF signaling is protective in hypoxia-induced pulmonary hypertension","volume":"131","author":"Woo","year":"2021","journal-title":"J Clin Invest"},{"key":"2026102312194891500_ref2","doi-asserted-by":"publisher","first-page":"104861","DOI":"10.1016\/j.phrs.2020.104861","article-title":"Diabetes and calcification: the potential role of anti-diabetic drugs on vascular calcification regression","volume":"158","author":"Ghosh","year":"2020","journal-title":"Pharmacol Res"},{"key":"2026102312194891500_ref3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41401-018-0042-6","article-title":"Vascular endothelial dysfunction, a major mediator in diabetic cardiomyopathy","volume":"40","author":"Knapp","year":"2019","journal-title":"Acta Pharmacol Sin"},{"key":"2026102312194891500_ref4","doi-asserted-by":"publisher","first-page":"95001","DOI":"10.1289\/EHP9321","article-title":"Key characteristics of cardiovascular toxicants","volume":"129","author":"Lind","year":"2021","journal-title":"Environ Health Perspect"},{"key":"2026102312194891500_ref5","doi-asserted-by":"publisher","first-page":"9191","DOI":"10.3390\/ijms22179191","article-title":"Hypoxia pathway proteins and their impact on the blood vasculature","volume":"22","author":"Rodriguez","year":"2021","journal-title":"Int J Mol Sci"},{"key":"2026102312194891500_ref6","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.tcb.2017.10.010","article-title":"Endothelial cell metabolism in health and disease","volume":"28","author":"Rohlenova","year":"2018","journal-title":"Trends Cell Biol"},{"key":"2026102312194891500_ref7","doi-asserted-by":"publisher","first-page":"106205","DOI":"10.1016\/j.phrs.2022.106205","article-title":"Phloretin ameliorates diabetes-induced endothelial injury through AMPK-dependent anti-EndMT pathway","volume":"179","author":"Mao","year":"2022","journal-title":"Pharmacol Res"},{"key":"2026102312194891500_ref8","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1161\/CIRCRESAHA.121.318011","article-title":"Inflammatory and biomechanical drivers of endothelial-interstitial interactions in calcific aortic valve disease","volume":"128","author":"Driscoll","year":"2021","journal-title":"Circ Res"},{"key":"2026102312194891500_ref9","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.21037\/atm-21-4566","article-title":"Weighted gene co-expression network analysis reveals specific modules and hub genes related to immune infiltration of osteoarthritis","volume":"9","author":"Cao","year":"2021","journal-title":"Ann Transl Med"},{"key":"2026102312194891500_ref10","doi-asserted-by":"publisher","first-page":"2357","DOI":"10.1161\/ATVBAHA.121.313788","article-title":"Endothelial-mesenchymal transition in cardiovascular disease","volume":"41","author":"Alvandi","year":"2021","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2026102312194891500_ref11","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1161\/CIRCRESAHA.120.316943","article-title":"Periostin: a potential therapeutic target for pulmonary hypertension?","volume":"127","author":"Nie","year":"2020","journal-title":"Circ Res"},{"key":"2026102312194891500_ref12","doi-asserted-by":"publisher","first-page":"2058","DOI":"10.1161\/CIRCULATIONAHA.110.972745","article-title":"Proteomic analysis of lung tissues from patients with pulmonary arterial hypertension","volume":"122","author":"Abdul-Salam","year":"2010","journal-title":"Circulation"},{"key":"2026102312194891500_ref13","doi-asserted-by":"publisher","first-page":"110915","DOI":"10.1016\/j.biopha.2020.110915","article-title":"Ginsenosides for the treatment of metabolic syndrome and cardiovascular diseases: pharmacology and mechanisms","volume":"132","author":"Fan","year":"2020","journal-title":"Biomed Pharmacother"},{"key":"2026102312194891500_ref14","doi-asserted-by":"publisher","first-page":"234","DOI":"10.21037\/atm-22-501","article-title":"A narrative review of the pharmacology of ginsenoside compound K","volume":"10","author":"Liu","year":"2022","journal-title":"Ann Transl Med"},{"key":"2026102312194891500_ref15","doi-asserted-by":"publisher","first-page":"1777145","DOI":"10.3389\/fphar.2026.1777145","article-title":"A review of the protection mechanisms of ginsenoside CK on cardiovascular disease and stroke","volume":"17","author":"Chan","year":"2026","journal-title":"Front Pharmacol"},{"key":"2026102312194891500_ref16","doi-asserted-by":"publisher","first-page":"28072","DOI":"10.1038\/s41598-025-13873-9","article-title":"Pharmacokinetic variability of 20(S)-protopanaxadiol-type ginsenosides Rb1, rd, and compound K from Korean red ginseng in experimental rodents","volume":"15","author":"Jeong","year":"2025","journal-title":"Sci Rep"},{"key":"2026102312194891500_ref17","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.3390\/nu15071626","article-title":"Inhibitory effects of ginsenoside compound K on lipopolysaccharide-stimulated inflammatory responses in macrophages by regulating SIRT1 and HDAC4","volume":"15","author":"Kang","year":"2023","journal-title":"Nutrients"},{"key":"2026102312194891500_ref18","doi-asserted-by":"publisher","first-page":"3633","DOI":"10.1111\/bph.70428","article-title":"Ginsenoside compound K up-regulates HADHB to promote fatty acid oxidation recovery and improve macrophage polarization in ulcerative colitis","volume":"183","author":"Liu","year":"2026","journal-title":"Br J Pharmacol"},{"key":"2026102312194891500_ref19","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.jgr.2021.12.008","article-title":"Compound K ameliorates airway inflammation and mucus secretion through regulation of PKC signaling in vitro and in vivo","volume":"46","author":"Lee","year":"2022","journal-title":"J Ginseng Res"},{"key":"2026102312194891500_ref20","doi-asserted-by":"publisher","first-page":"117661","DOI":"10.1016\/j.bcp.2025.117661","article-title":"Ginsenoside compound K exerts osteoprotective effects by suppressing osteoclastogenesis and promoting preosteoclast PDGF-BB-induced angiogenesis via targeting CSF1R","volume":"246","author":"Chen","year":"2026","journal-title":"Biochem Pharmacol"},{"key":"2026102312194891500_ref21","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.ejphar.2019.05.009","article-title":"Role of endothelin-1 clearance in the haemodynamic responses to endothelin-1 in the pulmonary and hindquarter vasculature of anaesthetised rats","volume":"855","author":"Angus","year":"2019","journal-title":"Eur J Pharmacol"},{"key":"2026102312194891500_ref22","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.3390\/ijms21041183","article-title":"The impact of hypoxia on neutrophil degranulation and consequences for the host","volume":"21","author":"Lodge","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2026102312194891500_ref23","doi-asserted-by":"publisher","first-page":"105725","DOI":"10.1016\/j.phrs.2021.105725","article-title":"Resveratrol and endothelial function: a literature review","volume":"170","author":"Parsamanesh","year":"2021","journal-title":"Pharmacol Res"},{"key":"2026102312194891500_ref24","doi-asserted-by":"publisher","first-page":"921864","DOI":"10.3389\/fimmu.2022.1105318","article-title":"IgA vasculitis update: epidemiology, pathogenesis, and biomarkers","volume":"13","author":"Xu","year":"2022","journal-title":"Front Immunol"},{"key":"2026102312194891500_ref25","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1042\/CS20080581","article-title":"Role of MCP-1 in cardiovascular disease: molecular mechanisms and clinical implications","volume":"117","author":"Niu","year":"2009","journal-title":"Clin Sci (Lond)"},{"key":"2026102312194891500_ref26","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.1161\/ATVBAHA.111.228999","article-title":"Endothelial differentiation: molecular mechanisms of specification and heterogeneity","volume":"31","author":"Atkins","year":"2011","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2026102312194891500_ref27","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.15252\/embj.201696150","article-title":"Endothelial cell metabolism in health and disease: impact of hypoxia","volume":"36","author":"Wong","year":"2017","journal-title":"EMBO J"},{"key":"2026102312194891500_ref28","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1093\/cvr\/cvz211","article-title":"Non-coding RNA in endothelial-to-mesenchymal transition","volume":"115","author":"Hulshoff","year":"2019","journal-title":"Cardiovasc Res"},{"key":"2026102312194891500_ref29","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1161\/CIRCRESAHA.120.318124","article-title":"MIR503HG loss promotes endothelial-to-mesenchymal transition in vascular disease","volume":"128","author":"Monteiro","year":"2021","journal-title":"Circ Res"},{"key":"2026102312194891500_ref30","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1172\/JCI93555","article-title":"Fibroblast heterogeneity: implications for human disease","volume":"128","author":"Lynch","year":"2018","journal-title":"J Clin Invest"},{"key":"2026102312194891500_ref31","doi-asserted-by":"publisher","first-page":"11607","DOI":"10.3390\/ijms222111607","article-title":"Cytoskeleton reorganization in EndMT: the role in cancer and fibrotic diseases","volume":"22","author":"Ciszewski","year":"2021","journal-title":"Int J Mol Sci"},{"key":"2026102312194891500_ref32","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.lfs.2017.07.014","article-title":"Endothelial to mesenchymal transition in the cardiovascular system","volume":"184","author":"Gong","year":"2017","journal-title":"Life Sci"},{"key":"2026102312194891500_ref33","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.tcm.2009.01.001","article-title":"Transforming growth factor beta-induced endothelial-to-mesenchymal transition: a switch to cardiac fibrosis?","volume":"18","author":"Goumans","year":"2008","journal-title":"Trends Cardiovasc Med"},{"key":"2026102312194891500_ref34","doi-asserted-by":"publisher","first-page":"S7","DOI":"10.1186\/1755-1536-5-S1-S7","article-title":"Molecular mechanisms of endothelial to mesenchymal cell transition in experimentally induced fibrotic diseases","volume":"5","author":"Piera-Velazquez","year":"2012","journal-title":"Fibrogenesis Tissue Repair"},{"key":"2026102312194891500_ref35","doi-asserted-by":"publisher","first-page":"114096","DOI":"10.1016\/j.biopha.2022.114096","article-title":"Recent advances in ginsenosides against respiratory diseases: therapeutic targets and potential mechanisms","volume":"158","author":"Ding","year":"2023","journal-title":"Biomed Pharmacother"},{"key":"2026102312194891500_ref36","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1158\/0008-5472.CAN-15-2556","article-title":"Transcriptional induction of periostin by a sulfatase 2-TGFbeta1-SMAD signaling axis mediates tumor angiogenesis in hepatocellular carcinoma","volume":"77","author":"Chen","year":"2017","journal-title":"Cancer Res"},{"key":"2026102312194891500_ref37","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1164\/rccm.201510-2032PP","article-title":"Roles of periostin in respiratory disorders","volume":"193","author":"Izuhara","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"2026102312194891500_ref38","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.atherosclerosis.2009.07.046","article-title":"Periostin mediates vascular smooth muscle cell migration through integrins alphaVbeta3 and alphaVbeta5 and focal adhesion kinase pathway","volume":"208","author":"Li","year":"2010","journal-title":"Atherosclerosis"},{"key":"2026102312194891500_ref39","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1186\/s12967-017-1298-1","article-title":"BDNF\/TrkB axis activation promotes epithelial-mesenchymal transition in idiopathic pulmonary fibrosis","volume":"15","author":"Cherubini","year":"2017","journal-title":"J Transl Med"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/78\/10\/rgag125\/72444156\/rgag125.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/78\/10\/rgag125\/72444156\/rgag125.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T16:19:53Z","timestamp":1792772393000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/doi\/10.1093\/jpp\/rgag125\/8994000"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":39,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jpp\/rgag125","relation":{},"ISSN":["2042-7158"],"issn-type":[{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,10]]},"published":{"date-parts":[[2026,10,1]]},"article-number":"rgag125"}}