{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:49:03Z","timestamp":1786121343870,"version":"build-2736575974"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To evaluate the clinical efficacy of Rhodiola rosea in high-altitude rheumatoid arthritis (RA) patients and to investigate,\n                      <jats:italic>in vitro<\/jats:italic>\n                      , whether its anti-inflammatory mechanism is mediated by the HIF-1\u03b1 signaling pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study adopted a retrospective analysis. Patients with RA in high-altitude areas were divided into the Rhodiola rosea treatment group (74 cases) and the conventional treatment group (86 cases). Baseline data, disease activity score (DAS28), inflammatory factors (CRP, ESR, TNF-\n                      <jats:italic>\u03b1<\/jats:italic>\n                      , and IL-6), serum HIF-1\u03b1 levels, imaging data, and adverse reaction monitoring data were collected to evaluate the clinical efficacy and safety of Rhodiola rosea. Human synovial cells (HFLS-RA) were used for\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments to establish a hypoxic model. Using CCK-8, qRT-PCR, Western Blot, and gene overexpression techniques, the molecular mechanism was further explored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The Rhodiola rosea treatment group showed significantly better improvements in DAS28, CRP, ESR, TNF-\n                      <jats:italic>\u03b1<\/jats:italic>\n                      , and IL-6 compared to the conventional treatment group (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05). Imaging assessment showed greater reductions in synovial thickness and blood-flow signals in the knee and metacarpophalangeal joints in the Rhodiola rosea group than in the conventional treatment group. The serum HIF-1\u03b1 level in the Rhodiola rosea group was significantly lower, and the incidence of adverse reactions (18.92%) was significantly lower than that of the conventional treatment group (34.88%), without any serious adverse events. The\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments showed that Rhodiola rosea injection (RRI) reduced hypoxia-induced expression of HIF-1\u03b1 and its downstream factors MMP-3, VEGF, COX-2, and ICAM-1.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Rhodiola rosea was associated with improved disease activity and inflammatory markers in high-altitude RA patients, with a favorable safety profile. The\n                      <jats:italic>in vitro<\/jats:italic>\n                      findings suggest that inhibition of HIF-1\u03b1 signaling may be one potential mechanism, although prospective and translational validation is still required.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1810329","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T04:22:23Z","timestamp":1786076543000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The clinical efficacy and mechanism of Rhodiola rosea in treating rheumatoid arthritis in high-altitude areas by regulating the HIF-1\u03b1 signaling pathway"],"prefix":"10.3389","volume":"13","author":[{"given":"Qin","family":"Li","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Qinghai Provincial Hospital of Traditional Chinese Medicine","place":["Xining, Qinghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangzhao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Qinghai Provincial Hospital of Traditional Chinese Medicine","place":["Xining, Qinghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenguang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Qinghai Provincial Hospital of Traditional Chinese Medicine","place":["Xining, Qinghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihai","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Qinghai Provincial Hospital of Traditional Chinese Medicine","place":["Xining, Qinghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyi","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Qinghai Provincial Hospital of Traditional Chinese Medicine","place":["Xining, Qinghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1007\/s10456-015-9477-2","article-title":"The pathogenic role of angiogenesis in rheumatoid arthritis","volume":"18","author":"Elshabrawy","year":"2015","journal-title":"Angiogenesis"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/s41584-020-0413-5","article-title":"Restoring synovial homeostasis in rheumatoid arthritis by targeting fibroblast-like synoviocytes","volume":"16","author":"Nygaard","year":"2020","journal-title":"Nat Rev Rheumatol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2764","DOI":"10.1002\/ptr.8187","article-title":"Comprehensive insights into rheumatoid arthritis: pathophysiology, current therapies and herbal alternatives for effective disease management","volume":"38","author":"Chatterjee","year":"2024","journal-title":"Phytother Res"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e28501","DOI":"10.1097\/MD.0000000000028501","article-title":"Consensus recommendations on managing the selected comorbidities including cardiovascular disease, osteoporosis, and interstitial lung disease in rheumatoid arthritis","volume":"101","author":"Yu","year":"2022","journal-title":"Medicine"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1051082","DOI":"10.3389\/fimmu.2022.1051082","article-title":"Systemic complications of rheumatoid arthritis: focus on pathogenesis and treatment","volume":"13","author":"Wu","year":"2022","journal-title":"Front Immunol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s40101-022-00283-3","article-title":"High prevalence of rheumatoid arthritis and its risk factors among Tibetan highlanders living in Tsarang, mustang district of Nepal","volume":"41","author":"Arima","year":"2022","journal-title":"J Physiol Anthropol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1186\/ar2568","article-title":"Hypoxia. The role of hypoxia and HIF-dependent signalling events in rheumatoid arthritis","volume":"11","author":"Muz","year":"2009","journal-title":"Arthritis Res Ther"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1633406","DOI":"10.3389\/fimmu.2025.1633406","article-title":"The role of hypoxic microenvironment in rheumatoid arthritis","volume":"16","author":"Zheng","year":"2025","journal-title":"Front Immunol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1538","DOI":"10.1080\/13880209.2021.1992449","article-title":"Salidroside orchestrates metabolic reprogramming by regulating the Hif-1\u03b1 signalling pathway in acute mountain sickness","volume":"59","author":"Yan","year":"2021","journal-title":"Pharm Biol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"422","DOI":"10.3724\/zdxbyxb-2022-0157","article-title":"Protective effect of salidroside on lung tissue in rats exposed rapidly to high altitude","volume":"51","author":"Wang","year":"2022","journal-title":"Zhejiang Da Xue Xue Bao Yi Xue Ban"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1080\/13880209.2020.1804407","article-title":"Chinese medicinal plants for the potential management of high-altitude pulmonary oedema and pulmonary hypertension","volume":"58","author":"Wang","year":"2020","journal-title":"Pharm Biol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"109552","DOI":"10.1016\/j.biopha.2019.109552","article-title":"Anti-inflammatory effects of Rhodiola rosea L.: a review","volume":"121","author":"Pu","year":"2020","journal-title":"Biomed Pharmacother"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"rgaf094","DOI":"10.1093\/jpp\/rgaf094","article-title":"Rosavin and salidroside attenuate microglia injury via nuclear factor \u03ba-B signaling pathway","volume":"78","author":"Liu","year":"2026","journal-title":"J Pharm Pharmacol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"5060","DOI":"10.1002\/fsn3.2459","article-title":"Protective effect of salidroside on hypoxia-related liver oxidative stress and inflammation via Nrf2 and JAK2\/STAT3 signaling pathways","volume":"9","author":"Xiong","year":"2021","journal-title":"Food Sci Nutr"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1608767","DOI":"10.3389\/fphar.2025.1608767","article-title":"Comprehensive profiling of Rhodiola rosea roots and corresponding products: phytochemical insights and modulation of neuroinflammation in BV2 microglial cell model","volume":"16","author":"Ko\u0142tun-Jasion","year":"2025","journal-title":"Front Pharmacol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1167\/iovs.62.9.25","article-title":"Salidroside prevents hypoxia-induced human retinal microvascular endothelial cell damage via miR-138\/ROBO4 Axis","volume":"62","author":"Shi","year":"2021","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"4318","DOI":"10.1007\/s10753-025-02328-y","article-title":"Salidroside alleviates renal ischemia-reperfusion injury by inhibiting macrophage Pyroptosis through HIF signaling","volume":"48","author":"Xueqiang","year":"2025","journal-title":"Inflammation"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"600186","DOI":"10.2147\/JIR.S600186","article-title":"Hypoxia-inducible factors in rheumatoid arthritis: central pathogenic roles and therapeutic opportunities","volume":"19","author":"Luo","year":"2026","journal-title":"J Inflamm Res"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.1038\/s41401-025-01520-y","article-title":"HIF-1alpha mediates mitochondrial damage by down-regulating ALKBH7 expression to promote the aberrant activation of FLS in rheumatoid arthritis","volume":"46","author":"Wang","year":"2025","journal-title":"Acta Pharmacol Sin"},{"key":"ref20","first-page":"1378","article-title":"Determination of salidroside and tyrosol content in large Rhodiola rosea injection by UPLC-MS\/MS method","volume":"35","author":"Zhi","year":"2019","journal-title":"Chin J Clin Pharmacol"},{"key":"ref21","first-page":"92","article-title":"Determination of salidroside content in large Rhodiola injection by UPLC method","volume":"36","author":"Du","year":"2017","journal-title":"Inner Mong J Tradit Chin Med"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"12293","DOI":"10.3390\/ijms241512293","article-title":"Phenolic compounds of Rhodiola rosea L. as the potential alternative therapy in the treatment of chronic diseases","volume":"24","author":"Bernatoniene","year":"2023","journal-title":"Int J Mol Sci"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"3142","DOI":"10.1039\/D0FO03061A","article-title":"The dietary supplement Rhodiola crenulata extract alleviates dextran sulfate sodium-induced colitis in mice through anti-inflammation, mediating gut barrier integrity and reshaping the gut microbiome","volume":"12","author":"Wang","year":"2021","journal-title":"Food Funct"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"31","DOI":"10.22038\/ijbms.2018.26994.6602","article-title":"Salidroside regulates the expressions of IL-6 and defensins in LPS-activated intestinal epithelial cells through NF-\u03baB\/MAPK and STAT3 pathways","volume":"22","author":"Wang","year":"2019","journal-title":"Iran J Basic Med Sci"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.neuropharm.2015.12.007","article-title":"Salidroside ameliorates arthritis-induced brain cognition deficits by regulating rho\/ROCK\/NF-\u03baB pathway","volume":"103","author":"Zhu","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"5053","DOI":"10.3390\/molecules28135053","article-title":"Rhodiola rosea L. extract, a known Adaptogen, evaluated in experimental arthritis","volume":"28","author":"Drafi","year":"2023","journal-title":"Molecules"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1136\/annrheumdis-2012-202444","article-title":"Hypoxia and hypoxia-inducible factor-1alpha provoke toll-like receptor signalling-induced inflammation in rheumatoid arthritis","volume":"73","author":"Hu","year":"2014","journal-title":"Ann Rheum Dis"},{"key":"ref28","first-page":"41","article-title":"Development on the interaction between hypoxia inducible factor-1\u03b1and nuclear factor-\u03baB in inflammatory hypoxic environment","volume":"43","author":"Xiuhui","year":"2020","journal-title":"Int J Biol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1007\/s40495-017-0106-1","article-title":"Rhodiola rosea L.: an herb with anti-stress, anti-aging, and immunostimulating properties for cancer chemoprevention","volume":"3","author":"Li","year":"2017","journal-title":"Curr Pharmacol Rep"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"151104","DOI":"10.1016\/j.bbrc.2024.151104","article-title":"Salidroside ameliorates macrophages lipid accumulation and atherosclerotic plaque by inhibiting Hif-1alpha-induced pyroptosis","volume":"742","author":"Guo","year":"2025","journal-title":"Biochem Biophys Res Commun"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/S1875-5364(25)60864-8","article-title":"Salidroside inhibits osteoclast differentiation based on osteoblast-osteoclast interaction via HIF-1a pathway","volume":"23","author":"Jin","year":"2025","journal-title":"Chin J Nat Med"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1007\/s00393-023-01431-5","article-title":"Salidroside suppresses cell growth and inflammatory response of fibroblast-like synoviocytes via inhibition of phosphoinositol-3 kinase\/threonine kinase signaling in rheumatoid arthritis","volume":"83","author":"Qin","year":"2024","journal-title":"Z Rheumatol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"2225868","DOI":"10.1080\/13510002.2023.2225868","article-title":"Salidroside affects the Th17\/Treg cell balance in aplastic anemia via the STAT3\/HIF-1alpha\/RORgammat pathway","volume":"28","author":"Liu","year":"2023","journal-title":"Redox Rep"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.ejphar.2018.07.031","article-title":"Hepatoprotective effect of rhein against methotrexate-induced liver toxicity","volume":"834","author":"Bu","year":"2018","journal-title":"Eur J Pharmacol"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1810329\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T04:22:24Z","timestamp":1786076544000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1810329\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":34,"alternative-id":["10.3389\/fmed.2026.1810329"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1810329","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]},"article-number":"1810329"}}