{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:08:26Z","timestamp":1785409706694,"version":"3.56.0"},"reference-count":194,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82574803"],"award-info":[{"award-number":["82574803"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81800575"],"award-info":[{"award-number":["81800575"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270672"],"award-info":[{"award-number":["82270672"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82574803"],"award-info":[{"award-number":["82574803"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["81800575"],"award-info":[{"award-number":["81800575"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82270672"],"award-info":[{"award-number":["82270672"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004829","name":"Sichuan Province Department of Science and Technology","doi-asserted-by":"publisher","award":["2022YFS0419"],"award-info":[{"award-number":["2022YFS0419"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Acute inflammatory disorders, including acute lung injury, acute pancreatitis, ischaemia\u2013reperfusion injury, and sepsis, are major clinical challenges characterised by rapid progression, a characteristic cytokine storm, and high mortality rates. The receptor for advanced glycation end-products (RAGE) serves as a pivotal multi-ligand pattern recognition receptor that integrates PAMPs and DAMPs. Excessive RAGE engagement triggers detrimental signalling cascades, notably NF-\u03baB and MAPKs, which exacerbate hyperinflammation and lead to progressive organ dysfunction. Consequently, the RAGE axis represents a potent therapeutic target for mitigating hyperinflammation and improving clinical outcomes in acute inflammatory disorders. While initial pharmacological efforts focused on synthetic inhibitors and biologics, there is a shifting focus toward bioactive alternatives with high safety profiles. Here, we present recent molecular insights into RAGE-mediated pathogenesis in acute inflammatory disorders and evaluate current therapeutic strategies. Furthermore, we emphatically summarise the bioactive natural products, including terpenoids, flavonoids, alkaloids, and a xanthone, that prevent and treat acute inflammatory disorders by disrupting RAGE\u2013ligand interactions and suppressing downstream oxidative stress and cytokine release. Integrating these molecular mechanisms with the pharmacological profiling of natural RAGE modulators provides a robust foundation for the development of next-generation therapeutic strategies to improve clinical outcomes in acute inflammatory disorders.<\/jats:p>","DOI":"10.3390\/biom16070929","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T10:01:17Z","timestamp":1782813677000},"page":"929","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RAGE Signalling in Acute Inflammatory Disorders: Therapeutic Potential of Natural Products"],"prefix":"10.3390","volume":"16","author":[{"given":"Qiqi","family":"Wang","sequence":"first","affiliation":[{"name":"West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Luo","sequence":"additional","affiliation":[{"name":"West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qihang","family":"Wan","sequence":"additional","affiliation":[{"name":"West China School of Medicine, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Li","sequence":"additional","affiliation":[{"name":"West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Latawiec","sequence":"additional","affiliation":[{"name":"Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Sutton","sequence":"additional","affiliation":[{"name":"Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5995-5432","authenticated-orcid":false,"given":"John","family":"Windsor","sequence":"additional","affiliation":[{"name":"Surgical and Translational Research Centre, Department of Surgery, Faculty of Medicine and Health Sciences, University of Auckland, Auckland 1142, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8659-322X","authenticated-orcid":false,"given":"Wei","family":"Huang","sequence":"additional","affiliation":[{"name":"West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"West China Biobank, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Institutes for Systems Genetics, Frontiers Science Centre for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Szatmary","sequence":"additional","affiliation":[{"name":"Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3GE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Liu","sequence":"additional","affiliation":[{"name":"West China Centre of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/S0140-6736(21)00439-6","article-title":"Acute respiratory distress syndrome","volume":"398","author":"Meyer","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1053\/j.gastro.2021.09.043","article-title":"Global Incidence of Acute Pancreatitis Is Increasing Over Time: A Systematic Review and 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