Anti-inflammatory and anti-arthritic effects of the ethanolic extract of Aralia continentalis Kitag. in IL-1β-stimulated human fibroblast-like synoviocytes and rodent models of polyarthritis and nociception

Background: Blocking the formation and invasive growth of pannus and its secretion of inflammatory cytokines and MMPs is important for treating rheumatoid arthritis. Hypothesis/Purpose: Anti-arthritic activity of Aralia continentalis Kitag., an oriental herbal medicine, and the underlying mechanisms involved were investigated. Study Design: Anti-inflammatory and anti-nocicpetive activities of the ethanolic extract (50% v/v) of Aralia continentalis Kitag. harvested from Imsil, Korea (ACI) were investigated in IL-1 beta-stimulated human fibroblast-like synoviocyte (FLS) cells and rodent models of collagen-induced polyarthritis and carrageenan-induced acute paw pain. Methods: In IL-1 beta-stimulated FLS cells derived from rheumatoid arthritis patients, the anti-inflammatory activity of ACI was examined by analyzing the expression levels of inflammatory mediators such as TNF-alpha, IL-6, IL-8, MMP-1, MMP-3, MMP-13, PGE2, and COX-2 using ELISA and RT-PCR analysis. The anti-arthritic activity of ACI was investigated by measuring body weight, squeaking score, paw volume, and arthritis index in collagen-induced polyarthritis mice. The anti-nociceptive activity of ACI was examined in the paw-pressure test and Tailflick latency test in rats. Results: The ethanolic extract (50% v/v) of ACI reduced the levels of TNF-alpha, IL-6, IL-8, MMP-1, and MMP-13 secreted by IL-1 beta-stimulated FLS cells, whereas MMP-3, COX-2, and PGE2 were not significantly affected. ACI inhibited the migration of NF-kappa B into the nucleus through the inhibition of ERK- and JNK-dependent MAP kinase pathways in IL-1 beta-stimulated FLS cells. In collagen-induced polyarthritis mice, oral administration of ACI extract (200 mg/kg) significantly alleviated arthritic behaviors. Histological observations of arthritic mouse knees were consistent with their behaviors. The anti-arthritic and anti-inflammatory activities of 200 mg/kg ACI extract were comparable to those of 10 mg/kg prednisolone when administered to mice. However, ACI administration did not significantly affect carrageenan-induced hyperalgesia or thermal nociception in rats. Conclusion: These results suggest that the ethanolic extract of ACI have significant anti-inflammatory and anti-arthritic effects in a rodent arthritis model and in IL-1 beta-stimulatedFLS cells. Thus, ACI may be a useful candidate for developing pharmaceuticals or dietary supplements for the treatment of inflammatory arthritis.