Anti-inflammatory and anti-nociceptive effect of Betula platyphylla var. japonica in human interleukin-1 beta-stimulated fibroblast-like synoviocytes and in experimental animal models

作者：Huh Jeong Eun; Hong Jang Mu; Baek Yong Hyeon; Lee Jae Dong; Choi Do Young; Park Dong Suk^*

来源：Journal of Ethnopharmacology, 2011, 135(1): 126-134.

DOI：10.1016/j.jep.2011.03.005

• Betula platyphylla var. japonica
• Anti-nociceptive
• Anti-inflammatory
• Anti-arthritis

Ethnopharmacological relevance: Traditional medicine has widely been used Betula platyphylla var. japonica to treat various inflammatory diseases including arthritis.
Aim of the study: To determine the anti-inflammatory, anti-nociceptive, and anti-arthritic effects of Betula platyphylla in interleukin-1 beta (IL-1 beta)-stimulated fibroblast-like synoviocytes from human rheumatoid arthritis and in nociceptive and inflammatory animal model.
Materials and methods: The inflammatory mediators such as IL-6, tumor necrosis factor (TNF)-alpha matrix metalloproteinase (MMP)-1, MMP-13, inducible nitric oxide synthesis (iNOS), nitrites, prostaglandin E-2 (PGE(2)) and cyclo-oxygenase 2 (COX-2) activity of Betula platyphylla were tested in IL-1 beta-stimulated fibroblast-like synoviocytes. Tail withdrawal in response to thermal stimulation in tail flick test or paw flinching and shaking in response to sc hind paw formalin injection was measured 1 h after oral administration of Betula platyphylla. The former was evaluated with a paw pressure test, and the latter was measured using the squeaking score, and paw volume in inflammatory arthritis tests.
Results: Betula platyphylla significantly inhibited proliferation of IL-1 beta-induced synoviocytes. Betula platyphylla reduced the levels of inflammatory mediators, such as IL-6, TNF-alpha, MMP-1, MMP13, and PGE2. In particular, Betula platyphylla significantly inhibited the releases of nitrites and iNOS, as well as release of NF kappa B, into the nucleus of IL-1 beta-treated synoviocytes, even at concentrations as low as 1 mu g/ml. Oral administrant of Betula platyphylla at 400 mg/kg significantly decreased about 27.8% of tail flick withdrawal and inhibited about the number of paw flinches in both phases 1 and 2 of the formalin test. In the carrageenan-induced acute pain and arthritis model, Betula platyphylla dose dependently reduced the nociceptive threshold and the arthritic symptoms at day 8, respectively, and Betula platyphylla at 400 mg/kg markedly reduced the inflammatory area about 48% in the ankle joints. This capacity of Betula platyphylla at 400 mg/kg was similar to that of the celecoxib-2 inhibitor in carrageenan-induced nociceptive and inflammatory arthritis model.
Conclusions: These results suggest that Betula platyphylla has anti-nociceptive and anti-inflammatory effects in IL-1 beta-stimulated RA FLS and in an animal model of arthritis. Thus, the use of Betula platyphylla as a pharmaceutical candidate for the treatment of arthritis should be further studied.

• 出版日期2011-4-26