PMID- 31431516 OWN - NLM STAT- MEDLINE DCOM- 20200918 LR - 20200918 IS - 1573-4935 (Electronic) IS - 0144-8463 (Print) IS - 0144-8463 (Linking) VI - 39 IP - 9 DP - 2019 Sep 30 TI - FM0807 decelerates experimental arthritis progression by inhibiting inflammatory responses and joint destruction via modulating NF-kappaB and MAPK pathways. LID - BSR20182263 [pii] LID - 10.1042/BSR20182263 [doi] AB - BACKGROUND: Rheumatoid arthritis (RA) is a chronic articular synovial inflammatory disease. The precise etiology underlying the pathogenesis of RA remains unknown. We aimed to investigate the inhibitory effect of curcumin analog FM0807 (curcumin salicylate monoester, 2-hydroxy-, 4-[(1E,6E)-7-(4-hydroxy-3-methoxyphenyl)-3,5-dioxo-1,6-heptadien-1-yl]-2-methoxyphenyl ester) on experimental RA and investigate its possible mechanisms of action. METHOD: Rats with Freund's complete adjuvant (FCA)-induced arthritis (AIA) were administered aspirin (0.1 mmol.kg(-1)), curcumin (0.1 mmol.kg(-1)), FM0807 (0.1, 0.2 mmol.kg(-1)) and vehicle via gastric gavage, from days 7 to 21, once daily. The hind paw volume and arthritis index (AI) were measured, and radiographic and histological examinations were performed. Twenty-one days later, the animals were killed and left ankle joints were removed to measure protein expression of the elements of the nuclear factor kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPK) pathway by Western blot analysis. The enzyme-linked immunosorbent assay (ELISA) was employed to measure synovial fluid levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-1beta and IL-10. RESULTS: Compared with AIA group, FM0807 reduced the AI and swelling of the injected hind paw in a dose-dependent manner, and inhibited increases in inflammatory cell infiltration, pannus formation and cartilage destruction. FM0807 also potently attenuated the increase in the expression of inflammatory factors TNF-alpha, IL-6 and IL-1beta in synovial fluid, while IL-10 levels were also elevated. FM0807 significantly suppressed phosphorylation of extracellular-signal-regulated kinase (ERK) 1/2 (ERK1/2), c-Jun-N-terminal kinase (JNK) 1/2 (JNK1/2), p38MAPK, inhibitor of NF-kappaB kinase (IKK), IkappaB and NF-kappaB p65 protein, (all P<0.05), which displayed more potential effects compared with those of the aspirin and curcumin groups. CONCLUSION: FM0807 exerts its therapeutic effects on RA by inhibiting cartilage degeneration. FM0807 treatment might be an effective therapeutic approach for RA. CI - (c) 2019 The Author(s). FAU - Zhang, Nanwen AU - Zhang N AUID- ORCID: 0000-0002-6711-1560 AD - School of Pharmacy, Fujian Medical University, Fuzhou, P.R. China. AD - Key Laboratory of Natural Medicine Pharmacology in Fujian Province, Fuzhou, P.R. China. FAU - Liu, Zhiwei AU - Liu Z AUID- ORCID: 0000-0001-7986-1628 AD - School of Clinical Medicine, Fujian Medical University, Fuzhou, P.R. China. FAU - Luo, Hongbin AU - Luo H AD - School of Pharmacy, Fujian Medical University, Fuzhou, P.R. China. AD - The First Affiliated Hospital of Fujian Medical University, Fuzhou, P.R. China. FAU - Wu, Weifang AU - Wu W AD - Department of anesthesia, Fuzhou Children's Hospital of Fujian Province, Fuzhou, P.R. China. FAU - Nie, Kaimei AU - Nie K AD - School of Pharmacy, Fujian Medical University, Fuzhou, P.R. China. FAU - Cai, Lin AU - Cai L AD - Department of anesthesia, Fuzhou Children's Hospital of Fujian Province, Fuzhou, P.R. China. FAU - Tan, Shuangyu AU - Tan S AD - School of Pharmacy, Fujian Medical University, Fuzhou, P.R. China. FAU - Chen, Xiaole AU - Chen X AD - School of Pharmacy, Fujian Medical University, Fuzhou, P.R. China 18259000966@126.com leochen5139@fjmu.edu.cn xjh@fjmu.edu.cn. AD - Key Laboratory of Natural Medicine Pharmacology in Fujian Province, Fuzhou, P.R. China. FAU - Huang, Ying AU - Huang Y AD - School of Pharmacy, Fujian Medical University, Fuzhou, P.R. China. FAU - Liu, Jiaxing AU - Liu J AD - School of Pharmacy, Fujian Medical University, Fuzhou, P.R. China. FAU - Lv, Meina AU - Lv M AD - School of Pharmacy, Fujian Medical University, Fuzhou, P.R. China. FAU - Zhang, Xin AU - Zhang X AD - School of Pharmacy, Fujian Medical University, Fuzhou, P.R. China. FAU - Fan, Yun AU - Fan Y AD - School of Pharmacy, Fujian Medical University, Fuzhou, P.R. China. FAU - Lin, Yuying AU - Lin Y AD - School of Pharmacy, Fujian Medical University, Fuzhou, P.R. China. FAU - Ye, Shennan AU - Ye S AD - The First Affiliated Hospital of Fujian Medical University, Fuzhou, P.R. China. FAU - Liu, Yang AU - Liu Y AD - School of Pharmacy, Fujian Medical University, Fuzhou, P.R. China. AD - Key Laboratory of Natural Medicine Pharmacology in Fujian Province, Fuzhou, P.R. China. FAU - Wu, Lixian AU - Wu L AUID- ORCID: 0000-0002-1300-6052 AD - School of Pharmacy, Fujian Medical University, Fuzhou, P.R. China 18259000966@126.com leochen5139@fjmu.edu.cn xjh@fjmu.edu.cn. AD - Key Laboratory of Natural Medicine Pharmacology in Fujian Province, Fuzhou, P.R. China. FAU - Xu, Jianhua AU - Xu J AD - School of Pharmacy, Fujian Medical University, Fuzhou, P.R. China 18259000966@126.com leochen5139@fjmu.edu.cn xjh@fjmu.edu.cn. AD - Key Laboratory of Natural Medicine Pharmacology in Fujian Province, Fuzhou, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190903 PL - England TA - Biosci Rep JT - Bioscience reports JID - 8102797 RN - 0 (Anti-Inflammatory Agents) RN - 0 (IL1B protein, rat) RN - 0 (Il6 protein, rat) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (NF-kappa B) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) RN - 9007-81-2 (Freund's Adjuvant) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - IT942ZTH98 (Curcumin) RN - R16CO5Y76E (Aspirin) SB - IM MH - Animals MH - Anti-Inflammatory Agents/chemical synthesis/*pharmacology MH - Arthritis, Experimental/chemically induced/*drug therapy/genetics/immunology MH - Aspirin/pharmacology MH - Curcumin/analogs & derivatives/chemical synthesis/*pharmacology MH - Disease Progression MH - Edema/chemically induced/genetics/immunology/*prevention & control MH - Freund's Adjuvant/administration & dosage/antagonists & inhibitors MH - Gene Expression Regulation/*drug effects MH - Hindlimb MH - Inflammation MH - Interleukin-10/genetics/immunology MH - Interleukin-1beta/genetics/immunology MH - Interleukin-6/genetics/immunology MH - MAP Kinase Signaling System/*drug effects MH - Male MH - Mitogen-Activated Protein Kinase 1/genetics/immunology MH - Mitogen-Activated Protein Kinase 3/genetics/immunology MH - NF-kappa B/genetics/immunology MH - Rats MH - Rats, Sprague-Dawley MH - Tarsus, Animal/drug effects/immunology/pathology MH - Tumor Necrosis Factor-alpha/genetics/immunology PMC - PMC6722489 OTO - NOTNLM OT - MAPK OT - NF-kappaB OT - inflammation OT - rat OT - rheumatoid arthritis COIS- The authors declare that there are no competing interests associated with the manuscript. EDAT- 2019/08/23 06:00 MHDA- 2020/09/20 06:00 PMCR- 2019/09/03 CRDT- 2019/08/22 06:00 PHST- 2018/12/04 00:00 [received] PHST- 2019/07/07 00:00 [revised] PHST- 2019/08/19 00:00 [accepted] PHST- 2019/08/23 06:00 [pubmed] PHST- 2020/09/20 06:00 [medline] PHST- 2019/08/22 06:00 [entrez] PHST- 2019/09/03 00:00 [pmc-release] AID - BSR20182263 [pii] AID - 10.1042/BSR20182263 [doi] PST - epublish SO - Biosci Rep. 2019 Sep 3;39(9):BSR20182263. doi: 10.1042/BSR20182263. Print 2019 Sep 30.