Clitoria ternatea flower petals: Effect on TNFR1 neutralization via downregulation of synovial matrix metalloproteases

•Significant quantities of flavonoids present in Clitoria ternatea flower.•Quercetin-3β-D-glucoside is capable of downregulating synovial MMP-2 activity in rheumatoid joints in mice.•Clitoria ternatea and quercetin-3β-D-glucoside facilitated antiarthritic effect of antibody mediated TNFR1 neutralization.

Ethnopharmacological relevanceClitoria ternatea Linn. (C. ternatea) is a traditionally used herb in arthritis, and its anti-arthritic activity has been attributed to polyphenols (e.g. quercetins) from its flower petal.Aim of the studyThe present study was designed to investigate whether C. ternatea or quercetin-3ß-D-glucoside (QG) support the antibody mediated TNFα-receptor 1 (TNFR1) neutralization to ameliorate arthritis in mice.Materials and methodsDevelopment of collagen-induced arthritis (CIA) in male Swiss mice (20-22 g, 3-4 weeks of age) was followed by estimation of synovial polymorphonuclear cell (PMN) accumulation (in terms of myeloperoxidase activity), synovial and systemic release of cytokines, chemokines and C-reactive protein (CRP) by enzyme-linked immunosorbent assay (ELISA), biochemical estimation of synovial free radical generation and antioxidant status, as well as immunoblot assessment of synovial TNFR1, toll-like receptor 2(TLR2), cyclooxygenase-2(COX-2) and inducible nitric oxide synthase (iNOS) expression; and zymographic analysis of synovial matrix-metalloprotease-2 (MMP-2) activity.ResultsCIA was induced from day 2 post-secondary immunizations as evidenced from arthritic scores and joint swelling in parallel to increased inflammatory and oxidative stress parameters in synovial joints. Long term supplementation with extract from Clitoria ternatea flower petals CTE (50 mg/kg) and QG (2.5 mg/kg) upto 24 days post booster immunization augmented anti-arthritic potential of TNFR1 neutralization with anti-TNFR1 antibody (10 μg per mice) in terms of reduced MPO activity, decrease in release of pro-inflammatory cytokines, chemokines, reactive oxygen species (ROS)/ reactive nitrogen species (RNS) production in parallel to significant (p<0.05) reduction in TNFR1, TLR2, iNOS, COX-2 and MMP-2 expression.ConclusionCTE and QG possess potential anti-arthritic activity which targets synovial MMP-2 in arthritic joints and TNFR1 targeting followed by CTE or QG treatment might become a combinatorial approach in future therapeutic research in treatment of arthritis.

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