Geroprotective efficacy of Triphalaguggul: a polyherbal formulation against inflammatory disorders through inhibition of pro-inflammatory cytokines as therapeutic biomarkers.

Abstract

Due to increase in life expectancy, aged population is growing exponentially, globally which has impact on human health as well as biomedical research. Research highlighted coordination between aging and arthritis where aging is the underlying hallmark of arthritis progression. Despite knowing the route of pathogenesis regarding most prevalent joint disorders like Osteoarthritis (OA) and rheumatoid arthritis (RA); efficient curable approach is still challenging. Worldwide 7-8% populations suffer from OA while 0.2-1% people are invaded by RA. Due to high cost, inadequate pharmacological action and adverse effects, NSAIDs are considered as secondary treatment option. Today, demographic changes towards polyherbal medicine usage targeting inhibition of pro-inflammatory cytokines are the challenge of the day. This study focused on Triphalaguggul (TG); a polyherbal formulation for treatment of arthritis targeting down regulation of pro-inflammatory cytokines and its signaling pathways. Toxicology study along with anti-OA and anti-RA evaluation in MIA and CFA induced rat model respectively. TG could reduce 96.15% inflamed knee, 95.18% paw edema and also helped in regrowth and rearrangement of chondrocytes properly in OA. In arthritic condition, increased hematological parameters like SGPT, SGOT, AlkP, CRP, RF were reinstated to normal range after treatment (p < 0.05). ELISA revealed that elevated IL-6, TNF-α, IL-1β were decreased after drug treatment (p < 0.05). Enhanced expression of p-JAK2, p-STAT3, NFκβ/p65 were downregulated (p < 0.05) after treatment which was validated by western blot and immunohistochemistry. Finding suggested that TG exhibited anti-arthritic activity down-regulating pro-inflammatory cytokines, JAK/STAT and NFƘβ signaling pathway as a therapeutic biomarker to protect from geriatric disease.