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.

Therapeutic Uses ofTriphalain Ayurvedic Medicine

“…In lipopolysaccharide-stimulated macrophages, Triphala treatment suppressed production of inflammatory mediators (such as TNFα, IL-1β, IL-6, MCP-1, VEGF, NO, and PGE2), intracellular free radicals, inflammatory enzymes (such as iNOS and COX-2), and lysosomal enzyme release. 70 Chebulagic acid, a constituent in Triphala , was found to inhibit COX and 5-LOX, which are both major enzymes involved in inflammation and carcinogenesis. 71 Triphala also increased antioxidant activity in mice after induction of nephrotoxicity from bromobenzene.…”

Anti‐Inflammatory Potential of Carpomitra costata Ethanolic Extracts via Inhibition of NF‐κB and AP‐1 Activation in LPS‐Stimulated RAW264.7 Macrophages

“…Inflammation is a defensive reaction in response to different stimuli, such as infection, chemical exposure, tissue damage, or other foreign substances [ 4 ]. However, excessive or inappropriate inflammatory responses can cause numerous chronic inflammatory disorders, including inflammatory bowel disease, cancer, atherosclerosis, and diabetes [ 5 , 6 ].…”

Modulatory Effects of Triphala and Manjistha Dietary Supplementation on Human Gut Microbiota: A Double-Blind, Randomized, Placebo-Controlled Pilot Study

“…4 Several studies have highlighted triphala-mediated anti-inflammatory effects that include decreased proinflammatory cytokine production. [5][6][7] Numerous in vitro studies have evaluated the antimicrobial effects of triphala. [8][9][10][11] Triphala extract demonstrated antibacterial activity against Escherichia coli, Klebsiella pneumoniae, and Salmonella typhi isolates from HIV infected patients.…”