{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T18:24:16Z","timestamp":1786991056155,"version":"build-2736575974"},"reference-count":41,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["International Immunopharmacology"],"published-print":{"date-parts":[[2025,2]]},"DOI":"10.1016\/j.intimp.2024.113973","type":"journal-article","created":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T12:37:53Z","timestamp":1736167073000},"page":"113973","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"special_numbering":"C","title":["Gentiopicroside ameliorates synovial inflammation and fibrosis in KOA rats by modulating the HMGB1-mediated PI3K\/AKT signaling axis"],"prefix":"10.1016","volume":"147","author":[{"given":"Yibao","family":"Wei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyuan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfeng","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiyang","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lishi","family":"Jie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deren","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peimin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"9","key":"10.1016\/j.intimp.2024.113973_b0005","first-page":"e721","article-title":"AAOS clinical practice guideline summary: management of osteoarthritis of the knee (nonarthroplasty), third edition","volume":"30","author":"Brophy","year":"2022","journal-title":"J. Am. Acad. Orthop. Surg."},{"issue":"1","key":"10.1016\/j.intimp.2024.113973_b0010","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13075-024-03309-6","article-title":"Targeting STAT6-mediated synovial macrophage activation improves pain in experimental knee osteoarthritis","volume":"26","author":"Blackler","year":"2024","journal-title":"Arthritis Res. Ther."},{"issue":"14","key":"10.1016\/j.intimp.2024.113973_b0015","article-title":"Chrysin ameliorates synovitis and fibrosis of osteoarthritic fibroblast-like synoviocytes in rats through PERK\/TXNIP\/NLRP3 signaling","volume":"20","author":"Ding","year":"2023","journal-title":"Front. Pharmacol."},{"issue":"1","key":"10.1016\/j.intimp.2024.113973_b0020","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.joca.2023.09.012","article-title":"Modulating mechanobiology as a therapeutic target for synovial fibrosis to restore joint lubrication","volume":"32","author":"Bonnevie","year":"2024","journal-title":"Osteoarthritis Cartilage"},{"issue":"7","key":"10.1016\/j.intimp.2024.113973_b0025","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1038\/nm.2807","article-title":"Mechanisms of fibrosis: therapeutic translation for fibrotic disease","volume":"18","author":"Wynn","year":"2012","journal-title":"Nat. Med."},{"issue":"11","key":"10.1016\/j.intimp.2024.113973_b0030","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.3390\/biomedicines11113047","article-title":"CD39+CD55-Fb subset exhibits myofibroblast-like phenotype and is associated with pain in osteoarthritis of the knee","volume":"11","author":"Tsuchiya","year":"2023","journal-title":"Biomedicines"},{"issue":"1","key":"10.1016\/j.intimp.2024.113973_b0035","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3390\/ijms19010076","article-title":"High-mobility group box 1 mediates fibroblast activity via RAGE-MAPK and NF-\u03baB signaling in keloid scar formation","volume":"19","author":"Kim","year":"2017","journal-title":"Int. J. Mol. Sci."},{"issue":"15","key":"10.1016\/j.intimp.2024.113973_b0040","doi-asserted-by":"crossref","first-page":"12143","DOI":"10.3390\/ijms241512143","article-title":"The role of alarmins in osteoarthritis pathogenesis: HMGB1, S100B and IL-33","volume":"24","author":"Palumbo","year":"2023","journal-title":"Int. J. Mol. Sci."},{"issue":"2_suppl","key":"10.1016\/j.intimp.2024.113973_b0045","doi-asserted-by":"crossref","first-page":"947S","DOI":"10.1177\/1947603520934858","article-title":"Glycyrrhizin, an HMGB1 inhibitor, suppresses interleukin-1\u03b2-induced inflammatory responses in chondrocytes from patients with osteoarthritis","volume":"13","author":"Zhou","year":"2021","journal-title":"Cartilage"},{"issue":"14","key":"10.1016\/j.intimp.2024.113973_b0050","article-title":"Olmesartan alleviates SARS-CoV-2 envelope protein induced renal fibrosis by regulating HMGB1 release and autophagic degradation of TGF-\u03b21","volume":"15","author":"Zhou","year":"2023","journal-title":"Front. Pharmacol."},{"issue":"2","key":"10.1016\/j.intimp.2024.113973_b0055","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.advms.2023.09.004","article-title":"The melatonin agonist ramelteon attenuates bleomycin-induced lung fibrosis by suppressing the NLRP3\/TGF-\u03921\/HMGB1 signaling pathway","volume":"68","author":"Aydin","year":"2023","journal-title":"Adv. Med. Sci."},{"issue":"1","key":"10.1016\/j.intimp.2024.113973_b0060","doi-asserted-by":"crossref","first-page":"11455","DOI":"10.1038\/s41598-023-38375-4","article-title":"Diacerein ameliorates cholestasis-induced liver fibrosis in rat via modulating HMGB1\/RAGE\/NF-\u03baB\/JNK pathway and endoplasmic reticulum stress","volume":"13","author":"Abdelfattah","year":"2023","journal-title":"Sci. Rep."},{"issue":"14","key":"10.1016\/j.intimp.2024.113973_b0065","doi-asserted-by":"crossref","first-page":"8743","DOI":"10.3390\/ijerph19148743","article-title":"Gly attenuates pulmonary fibrosis of silicosis by inhibiting the interaction between HMGB1 and BRG1 through PI3K\/Akt\/mTOR pathway","volume":"19","author":"Niu","year":"2022","journal-title":"Int. J. Environ. Res. Public Health"},{"issue":"8","key":"10.1016\/j.intimp.2024.113973_b0070","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/nrg1879","article-title":"The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism","volume":"7","author":"Engelman","year":"2006","journal-title":"Nat. Rev. Genet."},{"issue":"10","key":"10.1016\/j.intimp.2024.113973_b0075","doi-asserted-by":"crossref","DOI":"10.1096\/fj.202300944RR","article-title":"Nintedanib ameliorates osteoarthritis in mice by inhibiting synovial inflammation and fibrosis caused by M1 polarization of synovial macrophages via the MAPK\/PI3K-AKT pathway","volume":"37","author":"Yan","year":"2023","journal-title":"FASEB J."},{"issue":"1","key":"10.1016\/j.intimp.2024.113973_b0080","doi-asserted-by":"crossref","first-page":"62","DOI":"10.2174\/1389557516666160624124127","article-title":"Research progress of natural product gentiopicroside - a secoiridoid compound","volume":"17","author":"Wu","year":"2017","journal-title":"Mini Rev. Med. Chem."},{"key":"10.1016\/j.intimp.2024.113973_b0085","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2019.104559","article-title":"Gentiopicroside activates the bile acid receptor Gpbar1 (TGR5) to repress NF-kappaB pathway and ameliorate diabetic nephropathy","volume":"151","author":"Xiao","year":"2020","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.intimp.2024.113973_b0090","doi-asserted-by":"crossref","DOI":"10.2174\/0118761429251911231011092145","article-title":"Gentiopicroside ameliorated ductular reaction and inflammatory response in DDC-induced murine cholangiopathies model","author":"Hao","year":"2023","journal-title":"Curr. Mol. Pharmacol."},{"key":"10.1016\/j.intimp.2024.113973_b0095","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2022.154389","article-title":"Gentiopicroside alleviates cardiac inflammation and fibrosis in T2DM rats through targeting Smad3 phosphorylation","volume":"106","author":"Zou","year":"2022","journal-title":"Phytomedicine"},{"issue":"4","key":"10.1016\/j.intimp.2024.113973_b0100","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1111\/j.1365-2559.2006.02508.x","article-title":"Synovitis score: discrimination between chronic low-grade and high-grade synovitis","volume":"49","author":"Krenn","year":"2006","journal-title":"Histopathology"},{"key":"10.1016\/j.intimp.2024.113973_b0105","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2022.114121","article-title":"Effectiveness of losartan on infrapatellar fat pad\/synovial fibrosis and pain behavior in the monoiodoacetate-induced rat model of osteoarthritis pain","volume":"158","author":"Sriwatananukulkit","year":"2023","journal-title":"Biomed. Pharmacother."},{"issue":"1","key":"10.1016\/j.intimp.2024.113973_b0110","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s11033-018-4518-8","article-title":"Study of the mechanism underlying hsa-miR338-3p downregulation to promote fibrosis of the synovial tissue in osteoarthritis patients","volume":"46","author":"Song","year":"2019","journal-title":"Mol. Biol. Rep."},{"key":"10.1016\/j.intimp.2024.113973_b0115","doi-asserted-by":"crossref","DOI":"10.1093\/jmcb\/mjad005","article-title":"METTL3-mediated m6A modification of HMGA2 mRNA promotes subretinal fibrosis and epithelial-mesenchymal transition","author":"Wang","year":"2023","journal-title":"J. Mol. Cell Biol."},{"key":"10.1016\/j.intimp.2024.113973_b0120","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1111\/wrr.12939","article-title":"Fibroblast-like synoviocytes: Role in synovial fibrosis associated with osteoarthritis","volume":"29","author":"Maglaviceanu","year":"2021","journal-title":"Wound Repair Regen"},{"issue":"4","key":"10.1016\/j.intimp.2024.113973_b0125","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1016\/j.bbrc.2017.12.112","article-title":"Gentiopicroside ameliorates bleomycin-induced pulmonary fibrosis in mice via inhibiting inflammatory and fibrotic process","volume":"495","author":"Chen","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"4","key":"10.1016\/j.intimp.2024.113973_b0130","doi-asserted-by":"crossref","first-page":"320","DOI":"10.4062\/biomolther.2020.008","article-title":"Gentiopicroside ameliorates the progression from hepatic steatosis to fibrosis induced by chronic alcohol intake","volume":"28","author":"Yang","year":"2020","journal-title":"Biomol. Ther. (Seoul)"},{"key":"10.1016\/j.intimp.2024.113973_b0135","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2019.105840","article-title":"Therapeutic effects of gentiopicroside on adjuvant-induced arthritis by inhibiting inflammation and oxidative stress in rats","volume":"76","author":"Xie","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.intimp.2024.113973_b0140","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2022.108854","article-title":"Gentiopicroside attenuates collagen-induced arthritis in mice via modulating the CD147\/p38\/NF-\u03baB pathway","volume":"108","author":"Jia","year":"2022","journal-title":"Int. Immunopharmacol."},{"issue":"1","key":"10.1016\/j.intimp.2024.113973_b0145","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s10020-023-00717-3","article-title":"HMGB1 and Toll-like receptors: potential therapeutic targets in autoimmune diseases","volume":"29","author":"Ren","year":"2023","journal-title":"Mol. Med."},{"issue":"2","key":"10.1016\/j.intimp.2024.113973_b0150","doi-asserted-by":"crossref","first-page":"784","DOI":"10.7150\/ijbs.82003","article-title":"Inhibition of the HMGB1\/RAGE axis protects against cisplatin-induced ototoxicity via suppression of inflammation and oxidative stress","volume":"20","author":"Qiao","year":"2024","journal-title":"Int. J. Biol. Sci."},{"issue":"14","key":"10.1016\/j.intimp.2024.113973_b0155","article-title":"Soluble receptors for advanced glycation end-products prevent unilateral ureteral obstruction-induced renal fibrosis","volume":"16","author":"Kim","year":"2023","journal-title":"Front. Pharmacol."},{"issue":"313","key":"10.1016\/j.intimp.2024.113973_b0160","article-title":"Repositioning itraconazole for amelioration of bleomycin-induced pulmonary fibrosis: Targeting HMGB1\/TLR4 Axis, NLRP3 inflammasome\/NF-\u03baB signaling, and autophagy","volume":"15","author":"Elkhoely","year":"2023","journal-title":"Life Sci."},{"issue":"4","key":"10.1016\/j.intimp.2024.113973_b0165","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.cell.2017.07.029","article-title":"The PI3K pathway in human disease","volume":"170","author":"Fruman","year":"2017","journal-title":"Cell"},{"issue":"13","key":"10.1016\/j.intimp.2024.113973_b0170","article-title":"Oroxin B alleviates osteoarthritis through anti-inflammation and inhibition of PI3K\/AKT\/mTOR signaling pathway and enhancement of autophagy","volume":"1","author":"Lu","year":"2022","journal-title":"Front. Endocrinol. (Lausanne)"},{"issue":"8","key":"10.1016\/j.intimp.2024.113973_b0175","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1021\/acsmedchemlett.6b00119","article-title":"Discovery and pharmacological characterization of novel quinazoline-based PI3K delta-selective inhibitors","volume":"7","author":"Hoegenauer","year":"2016","journal-title":"ACS Med. Chem. Lett."},{"issue":"1","key":"10.1016\/j.intimp.2024.113973_b0180","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1186\/s13018-023-03717-5","article-title":"Daurisoline attenuates HO-induced chondrocyte autophagy by activating the PI3K\/Akt\/mTOR signaling pathway","volume":"18","author":"Zhang","year":"2023","journal-title":"J. Orthop. Surg. Res."},{"issue":"1","key":"10.1016\/j.intimp.2024.113973_b0185","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1186\/s13018-019-1394-4","article-title":"PI3K\/Akt inhibitor partly decreases TNF-\u03b1-induced activation of fibroblast-like synoviocytes in osteoarthritis","volume":"14","author":"Liu","year":"2019","journal-title":"J. Orthop. Surg. Res."},{"issue":"14","key":"10.1016\/j.intimp.2024.113973_b0190","article-title":"Tangeretin attenuates bleomycin-induced pulmonary fibrosis by inhibiting epithelial-mesenchymal transition via the PI3K\/Akt pathway","volume":"15","author":"Li","year":"2023","journal-title":"Front. Pharmacol."},{"issue":"1","key":"10.1016\/j.intimp.2024.113973_b0195","doi-asserted-by":"crossref","DOI":"10.1080\/0886022X.2024.2331612","article-title":"RfxCas13d-mediated inhibition of Circ1647 alleviates renal fibrosis via PI3K\/AKT signaling pathway","volume":"46","author":"Ni","year":"2024","journal-title":"Ren. Fail."},{"issue":"2","key":"10.1016\/j.intimp.2024.113973_b0200","doi-asserted-by":"crossref","DOI":"10.1016\/j.yexcr.2023.113522","article-title":"HMGB1 coordinates with Brahma-related gene 1 to promote epithelial-mesenchymal transition via the PI3K\/Akt\/mTOR pathway in BEAS-2B cells","volume":"424","author":"Deng","year":"2023","journal-title":"Exp. Cell Res."},{"issue":"25","key":"10.1016\/j.intimp.2024.113973_b0205","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.12659\/MSM.915690","article-title":"High-mobility group box 1 (HMGB1) promotes angiogenesis and tumor migration by regulating hypoxia-inducible factor 1 (HIF-1\u03b1) expression via the phosphatidylinositol 3-kinase (PI3K)\/AKT signaling pathway in breast cancer cells","volume":"1","author":"He","year":"2019","journal-title":"Med. Sci. Monit."}],"container-title":["International Immunopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576924024950?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576924024950?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T19:55:46Z","timestamp":1740599746000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1567576924024950"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":41,"alternative-id":["S1567576924024950"],"URL":"https:\/\/doi.org\/10.1016\/j.intimp.2024.113973","relation":{},"ISSN":["1567-5769"],"issn-type":[{"value":"1567-5769","type":"print"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Gentiopicroside ameliorates synovial inflammation and fibrosis in KOA rats by modulating the HMGB1-mediated PI3K\/AKT signaling axis","name":"articletitle","label":"Article Title"},{"value":"International Immunopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.intimp.2024.113973","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"113973"}}