Preprint / Version 1

Scientific validation of anti-arthritic effect of Kashayams – A polyherbal formulation in collagen induced arthritic rats

Authors

  • Aswathy S Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, 695581, Kerala, India
  • Santhi Krishnan Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, 695581, Kerala, India
  • Jasmine Peter Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, 695581, Kerala, India
  • Vidya Sabu Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, 695581, Kerala, India
  • A Helen Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, 695581, Kerala, India

Keywords:

Kashayams, Toll-like receptor -4, Anti-Arthritic, Nuclear factor kappa-light-chain-enhancer of activated B cells, Type II collagen, Rheumatoid arthritis

Abstract

Toll-like receptor-4 (TLR-4) mediates activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) resulting in induction of proinflammatory genes such as that encoding tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) which played a significant role in cartilage destruction of rheumatoid arthritis (RA). Low risk and better efficacy made herbal drugs more reliable than nonsteroid anti-inflammatory drugs (NSAIDS) in RA treatment. Gugguluthiktam Kashayam (GuK), Punarnavadi Kashayam (PuK) and Balaguluchiadi Kashayam (BgK) are ayurvedic polyherbal formulations prescribed in classical ayurvedic texts Sahasrayogam and Ashtangahridayam as medicines for the treatment of RA. Objective The objective of the present study was to elucidate the molecular mechanism of anti-arthritic effect of these Kashayams on TLR-4 signal transduction pathway in collagen induced arthritic rats. Material and methods The wistar rats grouped into group I - Normal, group II- Collagen induced arthritis (CIA), group III- CIA + BgK, group IV– CIA + PuK, group V- CIA + GuK, group VI - CIA + Indomethacin (3 mg/kg b.wt.). Treatment with Kashayam (2 ml/kg b.wt) started after 14 days of primary immunization with type II collagen and continued for a period of 45 days. Results Arthritis index, C-reactive protein (CRP), rheumatoid factor (RF) and myeloperoxidase (MPO) in serum and protein level of TLR-4, myeloid differentiation factor 88 (MYD88), NF-κB, TNF-α, IL-1β, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 COX-2) and prostaglandin E-2 (PGE-2) in cartilage were significantly elevated in CIA rats. Further, treatment with Kashayams downregulated all these inflammatory mediators hitherto TLR-4-NF-kB signal transduction pathway except IL-10, an anti-inflammatory cytokine which showed a reverse effect. Conclusion This molecular mechanism of the investigation confirmed the clinical efficacy of Kashayams in preventing the progression of RA and gave an intuition of the scientific validation of Kashayams, an Ayurvedic classical medicine. Keywords: Kashayams, Toll-like receptor -4, Anti-Arthritic, Nuclear factor kappa-light-chain-enhancer of activated B cells, Type II collagen, Rheumatoid arthritis

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