{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T06:19:43Z","timestamp":1783059583285,"version":"3.54.6"},"reference-count":119,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by hyperplasia of synovial pannus and progressive joint destruction. Pathological angiogenesis, driven by hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1), constitutes a core pathological mechanism and has become a critical therapeutic target for RA. This article systematically elucidates the molecular mechanisms by which HIF-1\u03b1 drives pathological angiogenesis through interactions with signaling pathways such as vascular endothelial growth factor (VEGF), angiogenin (ANG)-1\/2, CXC chemokine ligand 12 (CXCL12)\/CXC chemokine receptor 4 (CXCR4), phosphatidylinositol 3-kinase (PI3K)\/protein kinase B (Akt)\/mammalian target of rapamycin (mTOR). HIF-1\u03b1-mediated angiogenesis forms a positive feedback network with pathological processes including synovial inflammatory response, glycolytic metabolic reprogramming, and oxidative stress-mitochondrial damage, collectively promoting synovial pannus formation. Additionally, this article summarizes the effects of traditional Chinese medicine formulations and plant-derived monomeric metabolites on HIF-1\u03b1-mediated RA synovial angiogenesis, as well as the preclinical research advances of anti-angiogenic mechanisms. It also briefly explores the potential of novel botanical drugs delivery systems in enhancing the targeting of natural products to the HIF-1\u03b1 pathway and improving therapeutic efficacy, aiming to provide new perspectives and strategic options for HIF-1\u03b1-targeted RA therapies.<\/jats:p>","DOI":"10.3389\/fphar.2026.1793851","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:38:53Z","timestamp":1783057133000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanism of HIF-1\u03b1-mediated angiogenesis in rheumatoid arthritis and progress of natural medicine interventions"],"prefix":"10.3389","volume":"17","author":[{"given":"Yingjun","family":"Wei","sequence":"first","affiliation":[{"name":"Gansu University of Chinese Medicine","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingwen","family":"Xie","sequence":"additional","affiliation":[{"name":"Gansu Provincial Hospital of Traditional Chinese Medicine","place":["Lanzhou, China"]},{"name":"The First Affiliated Hospital of Gansu University of Chinese Medicine","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Hou","sequence":"additional","affiliation":[{"name":"Gansu Medical College","place":["Pingliang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingpeng","family":"Li","sequence":"additional","affiliation":[{"name":"Gansu University of Chinese Medicine","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhu","family":"Hou","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Gansu University of Chinese Medicine","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxiong","family":"Gao","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Gansu University of Chinese Medicine","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.tibs.2025.06.005","article-title":"The HIF axes in cancer: angiogenesis, metabolism, and immune-modulation","volume":"50","author":"Acu\u00f1a-Pilarte","year":"2025","journal-title":"Trends Biochem. 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