Carnosic acid inhibits inflammation response and joint destruction on osteoclasts, fibroblast‐like synoviocytes, and collagen‐induced arthritis rats

Journal of Cellular Physiology - Tập 233 Số 8 - Trang 6291-6303 - 2018
Mei Liu1, Xiaotian Zhou1, Lin Zhou2, Zhenzhou Liu1, Jinbo Yuan2, Jianwen Cheng3, Jinmin Zhao3, Long‐Fei Wu4, Hui Li1, Haiwen Qiu1, Jiake Xu3,2
1Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Nanjing Normal University, Nanjing, China
2School of Biomedical Sciences, University of Western Australia, Perth, Western Australia, Australia
3Research Centre for Regenerative Medicine and Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China
4Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, China

Tóm tắt

The discovery of new therapeutic drugs with the ability of preventing inflammation and joint destruction with less adverse effects is urgently needed for rheumatoid arthritis (RA). Carnosic acid (CA), a major phenolic compound isolated from the leaves of Rosemary (Rosmarinus officinalis L.), has been reported to have antioxidative and antimicrobial properties. However, its effects on RA have not been elucidated. Here, we investigated the effects of CA on osteoclasts and fibroblast‐like synoviocytes in vitro and on collagen‐induced arthritis (CIA) in Wistar rats in vivo. Our in vitro and in vivo studies showed that CA suppressed the expression of pro‐inflammatory cytokines including TNFɑ, IL‐1β, IL‐6, IL‐8, IL‐17 and MMP‐3, and downregulated the production of RANKL. More importantly, we observed that CA inhibited osteoclastogenesis and bone resorption in vitro and exerted therapeutic protection against joint destruction in vivo. Further biochemical analysis demonstrated that CA suppressed RANKL‐induced activations of NF‐κB and MAPKs (JNK and p38) leading to the downregulation of NFATc1. Taken together, our findings provide the convincing evidence that rosemary derived CA is a promising natural compound for the treatment of RA.

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Tài liệu tham khảo

10.1016/j.jep.2007.10.039

10.7326/M16-0713

10.1016/j.phytochem.2014.12.026

10.1016/j.jep.2006.09.008

10.1172/JCI8298

10.1016/j.foodchem.2005.10.011

10.1038/srep32001

10.1172/JCI200419657

10.1016/j.freeradbiomed.2016.05.020

10.1016/j.meatsci.2013.01.007

10.3390/molecules15117792

10.1038/nature02444

10.1210/endo.143.8.8954

Liu C., 2013, Triptolide prevents bone destruction in the collagen‐induced arthritis model of rheumatoid arthritis by targeting RANKL/RANK/OPG signal pathway, Evidence‐Based Complementary and Alternative Medicine, 2013, 1

10.1016/j.biomaterials.2014.04.006

10.1016/j.ajpath.2015.06.017

10.1093/carcin/23.6.983

10.1186/ar4305

10.1021/jf010693i

10.1074/jbc.M001229200

10.1074/jbc.M313973200

10.1038/nri2094

10.1083/jcb.148.2.333

10.1111/j.1600-065X.2009.00821.x

10.1136/annrheumdis-2016-210708

Rasoolijazi H., 2013, The protective role of carnosic acid against beta‐amyloid toxicity in rats, Scientific World Journal, 2013, 917082

10.1136/ard.2007.083188

10.7326/0003-4819-161-12-201412160-02009

10.1002/art.20382

10.1016/S0140-6736(14)61704-9

10.1089/jmf.2007.0524

10.1016/S1534-5807(02)00369-6

10.1038/nrrheum.2012.167

10.1002/1529-0131(199912)42:12<2532::AID-ANR5>3.0.CO;2-2

10.1089/jmf.2012.2577

10.1359/jbmr.2000.15.11.2178

10.1016/j.cytogfr.2008.11.007

Xu L., 2016, Interleukin‐29 enhances synovial inflammation and cartilage degradation in osteoarthritis, Mediators of Inflammation, 2016, 1, 10.1155/2016/9631510

10.1007/s11130-010-0166-4

10.1002/jsfa.4394

10.1007/s00394-008-0768-x

10.1002/jbmr.2771

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Journal of Cellular Physiology

Tập 233 Số 8

6291-6303

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