Alantolactone alleviates collagen-induced arthritis and inhibits Th17 cell differentiation through modulation of STAT3 signalling
| العنوان: | Alantolactone alleviates collagen-induced arthritis and inhibits Th17 cell differentiation through modulation of STAT3 signalling |
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| المؤلفون: | Shih-Chao Lin, Kuo-Tung Tang, Shiming Li, Hsiang-Lai Chen, Chi-Chien Lin |
| المصدر: | Pharmaceutical Biology, Vol 59, Iss 1, Pp 134-145 (2021) |
| بيانات النشر: | Informa UK Limited, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, inula helenium l, Cellular differentiation, Anti-Inflammatory Agents, Pharmaceutical Science, 030226 pharmacology & pharmacy, 01 natural sciences, Bone erosion, Arthritis, Rheumatoid, Lactones, Mice, 0302 clinical medicine, RAR-related orphan receptor gamma, Drug Discovery, STAT3, biology, rorγt, Chemistry, bone erosion, Cell Differentiation, General Medicine, Cell biology, Signalling, Mice, Inbred DBA, Cytokines, synovial hyperplasia, Molecular Medicine, Female, Signal Transduction, Collagen-induced arthritis, STAT3 Transcription Factor, il-17a, 03 medical and health sciences, il-6, Animals, Immunologic Factors, Sesquiterpenes, Eudesmane, Interleukin 6, Pharmacology, Inula, Dose-Response Relationship, Drug, lcsh:RM1-950, biology.organism_classification, Arthritis, Experimental, anti-inflammation, 0104 chemical sciences, Mice, Inbred C57BL, 010404 medicinal & biomolecular chemistry, lcsh:Therapeutics. Pharmacology, Complementary and alternative medicine, biology.protein, Th17 Cells |
| الوصف: | Context Alantolactone, the bioactive component in Inula helenium L. (Asteraceae), exhibits multiple biological effects. Objective We aimed to determine the anti-inflammatory effect of alantolactone in a collagen-induced arthritis (CIA) mouse model and its immunomodulatory effects on Th17 differentiation. Materials and methods A CIA mouse model was established with DBA/1 mice randomly divided into four groups (n = 6): healthy, vehicle and two alantolactone-treated groups (25 or 50 mg/kg), followed by oral administration of alantolactone to mice for 21 consecutive days after arthritis onset. The severity of CIA was evaluated by an arthritic scoring system and histopathological examination. Levels of cytokines and anti-CII antibodies as well as percentages of splenic Th17 and Th17 differentiation with or without alantolactone treatments (0.62, 1.2 or 2.5 μM) were detected with ELISA and flow cytometry, respectively. Western blot analysis was used to evaluate intracellular signalling in alantolactone-treated spleen cells. Results In CIA mice, alantolactone at 50 mg/kg attenuated RA symptoms, including high arthritis scores, infiltrating inflammatory cells, synovial hyperplasia, bone erosion and levels of the proinflammatory cytokines TNF-α, IL-6 and IL-17A, but not IL-10 in paw tissues. Alantolactone also reduced the number of splenic Th17 cells and the capability of naïve CD4+ T cells to differentiate into the Th17 subset by downregulating STAT3/RORγt signalling by as early as 24 h of treatment. Discussion and conclusions Alantolactone possesses an anti-inflammatory effect that suppresses murine CIA by inhibiting Th17 cell differentiation, suggesting alantolactone is an adjunctive therapeutic candidate to treat rheumatoid arthritis. |
| تدمد: | 1744-5116 1388-0209 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::701458ceb44510033e48c147313ca45bTest https://doi.org/10.1080/13880209.2021.1876102Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....701458ceb44510033e48c147313ca45b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17445116 13880209 |
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