Trikatu, an herbal compound ameliorates rheumatoid arthritis by the suppression of inflammatory immune responses in rats with adjuvant-induced arthritis and on cultured fibroblast like synoviocytes via the inhibition of the NFκB signaling pathway.
The present study was designed to investigate the potential therapeutic effect of trikatu, an herbal compound and its underlying molecular mechanism in rats with adjuvant-induced arthritis (AIA). Our results indicate that trikatu (1000 mg/kg/b.wt. oral) administration suppressed the production of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein (MCP)-1) and downregulated the mRNA expression levels of inflammatory mediators (TNF-α, IL-1β, IL-6, IL-17, MCP-1, receptor activator of nuclear factor kappa B ligand (RANKL), cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS)) and transcription factors (nuclear factor kappa B 65 (NFкB-p65) and activator protein-1 (AP-1)) in cultured AIA-fibroblast like synoviocytes and synovial tissue of AIA rats. Consistently, the protein expression of NFкB-p65, IL-17, TNF-α, COX-2, and RANKL was also dramatically reduced in cultured AIA-fibroblast like synoviocytes and synovial tissue of AIA rats by trikatu treatment. In addition, trikatu suppressed the expression and phosphorylation of NFкB-p65 similar to the Bay 11-7082 (NFкB inhibitor) in cultured AIA-fibroblast like synoviocytes. Furthermore, trikatu alleviated the histopathology of joint of arthritic rats. Overall, these data highlights that trikatu could be a promising alternative modality for the possible treatment of rheumatoid arthritis and other inflammatory diseases.
Immunopathology Lab, School of Bio Sciences and Technology, VIT University, Vellore 632 014, Tamil Nadu, India.
Hari Madhuri
HM
Doss
Immunopathology Lab, School of Bio Sciences and Technology, VIT University, Vellore 632 014, Tamil Nadu, India.
Ramamoorthi
R
Ganesan
Immunopathology Lab, School of Bio Sciences and Technology, VIT University, Vellore 632 014, Tamil Nadu, India. Electronic address: mkr474@gmail.com.
Mahaboobkhan
M
Rasool
D000475:Alkenes / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015153:Blotting, Western; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D008401:Gas Chromatography-Mass Spectrometry; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D008517:Phytotherapy; D010880:Piperidines / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013583:Synovial Membrane / Q000187:drug effects / Q000473:pathology; D000070918:Synoviocytes / Q000187:drug effects / Q000473:pathology*
D000475:Alkenes; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D010880:Piperidines; D012333:RNA, Messenger; C540456:trikatu
Fibroblast-like synoviocytes; IL-17; Inflammatory mediators; NFкB; Rheumatoid arthritis; Trikatu