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

Phytomedicine. 2018 Jan 1;38:45-56. doi: 10.1016/j.phymed.2017.10.016. Epub 2017 Nov 8.

Abstract

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-1β-stimulated human fibroblast-like synoviocyte (FLS) cells and rodent models of collagen-induced polyarthritis and carrageenan-induced acute paw pain.

Methods: In IL-1β-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-α, 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 Tail-flick latency test in rats.

Results: The ethanolic extract (50% v/v) of ACI reduced the levels of TNF-α, IL-6, IL-8, MMP-1, and MMP-13 secreted by IL-1β-stimulated FLS cells, whereas MMP-3, COX-2, and PGE2 were not significantly affected. ACI inhibited the migration of NF-κB into the nucleus through the inhibition of ERK- and JNK-dependent MAP kinase pathways in IL-1β-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-1β-stimulated FLS cells. Thus, ACI may be a useful candidate for developing pharmaceuticals or dietary supplements for the treatment of inflammatory arthritis.

Keywords: Aralia continentalis Kitag.; Fibroblast-like synoviocyte; Inflammation; Inflammatory cytokine; Matrix metalloproteinase; Rheumatoid arthritis.

MeSH terms

  • Analgesics, Non-Narcotic / pharmacology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Aralia / chemistry*
  • Arthritis / chemically induced
  • Arthritis / drug therapy*
  • Arthritis, Experimental / drug therapy
  • Arthritis, Rheumatoid / drug therapy
  • Cytokines / metabolism
  • Humans
  • Inflammation Mediators / metabolism
  • Interleukin-1beta / pharmacology
  • Male
  • Mice, Inbred DBA
  • NF-kappa B / metabolism
  • Nociception / drug effects
  • Pain / drug therapy
  • Rats, Sprague-Dawley
  • Republic of Korea
  • Synoviocytes / drug effects*
  • Synoviocytes / metabolism
  • Synoviocytes / pathology

Substances

  • Analgesics, Non-Narcotic
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Inflammation Mediators
  • Interleukin-1beta
  • NF-kappa B