Association of Activation of Induced COX-2, iNOS and Cytokines with NF-kappa B Depression by Taiwan Wild Grape Ethanolic Extract in Mice.

Taiwan wild grape (Vitis thunbergii var. taiwaniana; VTT) is an important traditional herbal medicine used to treat muscle injuries and acute and chronic pain of the ligaments. Information on its bioactivity and the underlying mechanisms, which have not been elucidated thus far, is needed to demonstrate its value for pharmacological and clinical use. This study presents evidence to clarify the antinociceptive and anti-inflammatory activities of an ethanolic extract of VTT stem (VTTEtOH) and the possible molecular mechanisms involved in such biactivities. In the mice, VTTEtOH significantly reduced the acetic acid-induced writhing response (P < 0.01), formalin-induced licking time (P < 0.01), and edema paw volume at 4 and 5 h after λ-carrageenan injection. VTTEtOH obviously decreased the levels of tumor necrosis factor alpha (P < 0.01), interleukin (IL)-1β (P < 0.05), interleukin (IL)-6 (P < 0.001), nuclear factor-kappa B (P < 0.001), iNOS (P < 0.001), cyclooxygenase-2 (P < 0.001) and Nitric oxide (P < 0.001) in edema-paw tissue. The molecular mechanisms underlying these effects might involve significant inhibition of the activity of cyclooxygenase-2 through suppression of nuclear factor-kappa B and inducible nitric oxide synthase expression and reduction of the levels of various inflammatory mediators, including tumor necrosis factor alpha, interleukin (IL)-1β, IL-6, and nitric oxide. Our findings provided pharmacological and histopathological evidences that VTTEtOH alleviates inflammatory pain-related diseases.