Modulation of Th1/Th2 cytokines and inflammatory mediators by hydroxychavicol in adjuvant induced arthritic tissues |
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Authors: | Anjali Pandey Sarang Bani Prabhu Dutt Krishna Avtar Suri |
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Institution: | 1. Department of Biology, Georgia State University, Atlanta, GA 30303, USA;2. Advinus Therapeutics, Karnataka, India;3. Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA |
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Abstract: | The present study was undertaken to investigate the anti-arthritic activity of hydroxychavicol (HC) a major phenolic compound isolated from the aqueous extract leaves of plant Piper betle (Piperaceae). The compound showed significant lowering of pro-inflammatory (Th1) cytokine levels in arthritic paw tissue homogenate supernatant viz. IL-2, IFN-γ, and TNF-α with maximum inhibition at higher dose levels of 2 and 4 mg/kg p.o. and enhanced the production of anti-inflammatory (Th2) cytokines IL-4 and IL-5 estimated by cytometric bead array immunoassay. Cytometric bead array uses the sensitivity of amplified fluorescence detection by flowcytometer to measure soluble analytes in a particle based immune assay. This assay can accurately quantitate five cytokines in a 50-μl sample volume. The T-helper (Th1) deviated cells produce detectable level of tumor necrosis factor (TNF-α), interleukin-2 (IL-2), and interferon-gamma (IFN-γ), while the Th2 deviated cells produce significant amount of interleukin-4 (IL-4) and interleukin-5 (IL-5). HC at graded doses also significantly decreased the expression of IL-1β, PGE2, LTB4, and nitric oxide levels showing significant inhibition of these parameters. Elevated levels of CD4+ T cell specific interferon-gamma (IFN-γ) in splenocytes of arthritic animals was also inhibited in treated animals. The oral LD0 in both mice and rats was more than 1000 mg/kg. |
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