title: Majoon ushba, a polyherbal compound, suppresses pro-inflammatory mediators and RANKL expression via modulating NFкB and MAPKs signaling pathways in fibroblast-like synoviocytes from adjuvant-induced arthritic rats.
abstract: Fibroblast-like synoviocytes (FLS) are inhabitant mesenchymal cells of synovial joints and have been recognized to play an imperative role in the immunopathogenesis of rheumatoid arthritis (RA). Blocking these pathological roles of FLS provides a potentially important therapeutic strategy for the treatment for RA. A recent study had confirmed that majoon ushba (MU), a polyherbal unani compound, possesses anti-arthritic effects in in vivo. Toward this direction, an effort has been made to understand the effect of MU on FLS derived from adjuvant-induced arthritis (AIA) rats. Here, we observed that MU administration (100-300 µg/ml) significantly inhibited the expression and phosphorylation of NFкB-p65 protein similar to that of the Bay 11-7082 (NFкB inhibitor) in NFкB signaling pathway and suppressed the protein expression of ERK1/2 and JNK1/2 in MAPKs signaling pathway in AIA-FLS. In addition, the protein expression of TNF-α, IL-17, RANKL, and iNOS was also found reduced. MU treatment significantly inhibited the mRNA expression of pro-inflammatory mediators (TNF-α, IL-1β, IL-6, MCP-1, IL-17, iNOS, and COX-2), transcription factors (NFкB-p65 and AP-1), and RANKL and attenuated the overproduction of TNF-α, IL-1β, IL-6, and MCP-1 (ELISA) in AIA-FLS. Furthermore, MU treatment significantly inhibited the level of lipid peroxidation, lysosomal enzymes release, and glycoproteins and increased antioxidant status (superoxide dismutase and catalase) in AIA-FLS. In conclusion, the results of this study provide evidence that MU possesses anti-inflammatory effect against AIA-FLS through the decrease in pro-inflammatory mediators expression by suppressing NFкB and MAPKs signaling pathways.
authors.affiliation: SMV 240, Immunopathology Lab, School of Bio Sciences and Technology, VIT University, Vellore, Tamilnadu, 632 014, India.
authors.forename: Ramamoorthi
authors.initials: R
authors.lastname: Ganesan
authors.affiliation: SMV 240, Immunopathology Lab, School of Bio Sciences and Technology, VIT University, Vellore, Tamilnadu, 632 014, India.
authors.forename: Hari Madhuri
authors.initials: HM
authors.lastname: Doss
authors.affiliation: SMV 240, Immunopathology Lab, School of Bio Sciences and Technology, VIT University, Vellore, Tamilnadu, 632 014, India. mkr474@gmail.com.
authors.forename: Mahaboobkhan
authors.initials: M
authors.lastname: Rasool
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000276:immunology / Q000628:therapy*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D028321:Plant Preparations / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D000070918:Synoviocytes / Q000276:immunology* / Q000382:microbiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D016328:NF-kappa B; D028321:Plant Preparations; C000610643:majoon ushba; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Fibroblast-like synoviocytes; Majoon ushba; NFкB; Pro-inflammatory cytokines; Rheumatoid arthritis