title: Triphala herbal extract suppresses inflammatory responses in LPS-stimulated RAW 264.7 macrophages and adjuvant-induced arthritic rats via inhibition of NF-κB pathway.
abstract: This study sought to explore the mechanism of anti-inflammatory effect of triphala in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and in adjuvant-induced arthritic rats. In stimulated RAW 264.7 cells, triphala (100-300 μg/ml) significantly suppressed production of inflammatory mediators (e.g. TNFα, IL-1β, IL-6, MCP-1, VEGF, NO, PGE2), intracellular free radicals and release of lysosomal enzymes (e.g. acid phosphatase, β-galactosidase, N-acetyl glucosamindase and cathepsin D) in a dose-related manner. With triphala, mRNA levels of genes for pro-inflammatory TNFα, IL-1β, IL-6 and MCP-1, inflammatory iNOS and COX-2 enzymes and NF-κBp65 were down-regulated in the stimulated cells; in contrast, there was up-regulation of heme oxygenase-1 (HO-1) expression. Western blot analyses revealed that triphala suppressed the protein expression of NF-κB p65 and p-NF-κB p65 in the stimulated cells, which subsequently reduced over-expression of TNFα, IL-17, iNOS and COX-2 in a manner similar to that observed with BAY 11-7082, an IκB kinase inhibitor. Immunofluorescence analysis revealed inhibition of p-NF-κB p65 nuclear translocation and COX-2 protein expression caused by triphala. Consistent with these findings, the animal studies presented confirmed that triphala exhibited anti-inflammatory effects in a rat adjuvant-induced arthritis model by reducing of inflammatory mediator (e.g. IL-17, COX-2 and RANKL) expression via inhibition of NF-κB activation. Taken together, the results here demonstrated that triphala has potential anti-inflammatory applications that could be used for the treatment of inflammatory disorders, including rheumatoid arthritis.
authors.affiliation: a Immunopathology Lab , School of Bio Sciences and Technology, VIT University , Vellore , India.
authors.forename: Sowmiya
authors.initials: S
authors.lastname: Kalaiselvan
authors.affiliation: a Immunopathology Lab , School of Bio Sciences and Technology, VIT University , Vellore , India.
authors.forename: Mahaboob Khan
authors.initials: MK
authors.lastname: Rasool
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008515:Medicine, Ayurvedic; D051379:Mice; D010936:Plant Extracts / Q000627:therapeutic use*; D000067996:RAW 264.7 Cells; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; C520904:triphala; D051546:Cyclooxygenase 2
keywords: Inflammation; inflammatory mediators; pro-inflammatory cytokines; triphala