Preclinical evaluation of 3,4-dimethoxybenzoic acid alone and in combination for adjuvant-induced arthritis in Wistar rats.

Abstract

Background: Rheumatoid arthritis is a systemic autoimmune disorders of joints. Its available therapies having serious adverse effects, high cost and poor patient compliance.

Objective: The present study aimed to evaluate the anti-inflammatory and anti-arthritic potential of 3, 4-dimethoxybenzoic acid or Veratric acid (VA) by in-vitro and in-vivo assays. Additionally, acute toxicity of VA was performed.

Methodology: The anti-inflammatory activity was assessed by Xylene-induced ear edema, and Carrageenan-induced paw edema models in Wistar rats. The VA was given at doses of 20, 40, and 80 mg/kg, with Piroxicam (10mg/kg) as standard drug. For anti-arthritic action, 0.1 ml of Complete Freund's adjuvant was intradermally inoculated in left posterior paw on first day while treatment with VA at 20, 40, 80, and VA 80 mg/kg + methotrexate and methotrexate (1 mg/kg) as standard drug were given orally on the 8th day for 21 days.

Results: Treatment with VA exhibited a substantial reinstatement of body weight, paw edema, arthritic scores, and oxidative stress in difference to disease control. All treatment groups exhibited notable down-regulation (p < .0001) of IL-6, TNF-α, IL-β, COX-2, and NF-κB and up-regulation of IL-10, 1-κβ, IL-4 in contrast to disease control. The combination group had exhibited noticeable anti-arthritic potential in comparison to individual treatment groups. In acute toxicity study, LD₅₀ of VA was greater than 2000 mg/kg.

Conclusion: It can be inferenced from data that VA can be safely used to treat arthritis especially in combination with MTX but it should be further evaluated in combination for long term use.