Anti-arthritogenic effect of Saponin-1 by alteration of Th1/Th2 cytokine paradigm in arthritic mice

• Study was carried out to explore anti arthritic effect of SAP-1 Parthenium hysterophorus. SAP-1 suppresses Th1 and stimulates Th2 cytokine expression.
• Significant decrease in circulating Th17 suggests down-regulation of both Th17-related cytokine and TNF-α as one of the mechanisms of SAP-1 therapy.
• It inhibited CD4+CD25+ T cells and suppressed pro-inflammatory mediators like IL-1β and NO.
• SAP-1 decreased the elevated concentration of both COX-2 and MCP-1 in arthritic animals.
• SAP-1 leads to neutralization of pro-inflammatory cytokines that control arthritis, leading to modulating cytokine balance as therapeutic strategy.

Objective & designInvestigation was carried out on Saponin 1 (SAP-1), a novel molecule isolated from Parthenium hysterophorus, on proinflammatory (Th1) & anti-inflammatory (Th2) cytokines in blood of arthritic balb/c mice.MethodsAdjuvant induced developing inflammatory arthritis was induced in mice which were treated with SAP-1 in graded oral doses. The molecular markers were determined using Flow Cytometry which uses sensitivity of amplified fluorescence detection to measure soluble analytes in particle based immune assay. The T-helper (Th1) deviated cells produce detectable level of Tumor necrosis factor (TNF-alpha), interleukin-2 (IL-2) & interferon-gamma (IFN-gamma), while the Th2 deviated cells produce significant amount of interleukin-4 (IL-4) and interleukin-5 (IL-5).ResultsSAP-1 at graded oral doses inhibited expression of IFN-gamma & TNF-alpha in serum & correspondingly increased expression of IL-4 significantly. SAP-1 also inhibited IL-17 and CD4+CD25+ cell population showing to have suppressive effect on Th-17 pathway as well as T-regulatory cells. It also suppressed the increased levels of pro-inflammatory mediators like IL-1β and NO. Inhibitors of Cox-2 and MCP-1 provide effective improvements in signs and symptoms of Rheumatoid Arthritis. SAP-1 decreased the elevated concentration of both COX-2 and MCP-1 in arthritic animals.ConclusionsSAP-1 diminishes Th1 immunity activation, a primary cause of arthritis, in favour of Th2 dominance, which reduces arthritic condition in mice displaying immune-modulatory potential.