{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T18:31:09Z","timestamp":1784658669997,"version":"3.55.0"},"reference-count":37,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Guangxi","award":["2018GXNSFDA050016"],"award-info":[{"award-number":["2018GXNSFDA050016"]}]},{"name":"Natural Science Foundation of Guangxi","award":["2018GXNSFBA281094"],"award-info":[{"award-number":["2018GXNSFBA281094"]}]},{"name":"Special Funds for Local Science and Technology Development Guided by the Central Committee","award":["ZY20111010"],"award-info":[{"award-number":["ZY20111010"]}]},{"name":"Guangxi Innovation-driven Development Special Project","award":["Guike AA18118015"],"award-info":[{"award-number":["Guike AA18118015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Callicarpalongissima has been used as a Yao folk medicine to treat arthritis for years in China, although its active anti-arthritic moieties have not been clarified so far. In this study, two natural phenolic diterpenoids with anti-rheumatoid arthritis (RA) effects, rosmanol and carnosol, isolated from the medicinal plant were reported on for the first time. In type II collagen-induced arthritis DBA\/1 mice, both rosmanol (40 mg\/kg\/d) and carnosol (40 mg\/kg\/d) alone alleviated the RA symptoms, such as swelling, redness, and synovitis; decreased the arthritis index score; and downregulated the serum pro-inflammatory cytokine levels of interleukin 6 (IL-6), monocyte chemotactic protein 1 (MCP-1), and tumor necrosis factor \u03b1 (TNF-\u03b1). Additionally, they blocked the activation of the Toll-like receptor 4 (TLR4)\/nuclear factor \u03baB (NF-\u03baB)\/c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways. Of particular interest was that when they were used in combination (20 mg\/kg\/d each), the anti-RA effect and inhibitory activity on the TLR4\/NF-\u03baB\/MAPK pathway were significantly enhanced. The results demonstrated that rosmanol and carnosol synergistically alleviated RA by inhibiting inflammation through regulating the TLR4\/NF-\u03baB\/MAPK pathway, meaning they have the potential to be developed into novel, safe natural combinations for the treatment of RA.<\/jats:p>","DOI":"10.3390\/molecules27010078","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T21:40:21Z","timestamp":1640295621000},"page":"78","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Rosmanol and Carnosol Synergistically Alleviate Rheumatoid Arthritis through Inhibiting TLR4\/NF-\u03baB\/MAPK Pathway"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1186-5742","authenticated-orcid":false,"given":"Lianchun","family":"Li","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization, Guangxi Institute of Botany, Chinese Academy of Sciences, Guilin 541006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghong","family":"Pan","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization, Guangxi Institute of Botany, Chinese Academy of Sciences, Guilin 541006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desheng","family":"Ning","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization, Guangxi Institute of Botany, Chinese Academy of Sciences, Guilin 541006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxia","family":"Fu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization, Guangxi Institute of Botany, Chinese Academy of Sciences, Guilin 541006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1016\/S0140-6736(10)60826-4","article-title":"Rheumatoid arthritis","volume":"376","author":"Scott","year":"2010","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105618","DOI":"10.1016\/j.phrs.2021.105618","article-title":"Phytochemical add-on therapy to DMARDs therapy in rheumatoid arthritis: In vitro and in vivo bases, clinical evidence and future trends","volume":"169","author":"Kour","year":"2021","journal-title":"Pharmacol. 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