Journal
JOURNAL OF PHARMACY AND PHARMACOLOGY
Volume 65, Issue 1, Pages 115-122Publisher
WILEY
DOI: 10.1111/j.2042-7158.2012.01568.x
Keywords
activated neutrophils; air pouch model; ss-sitosterol; calcium uptake
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Funding
- 'Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)', Brazil
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Objectives To evaluate the effect of beta-sitosterol on 45Ca2+ uptake in activated murine neutrophils, and upon myeloperoxidase and adenosine deaminase activity, and interleukin-1 beta (IL-1 beta) and tumour necrosis factor-a (TNF-a) levels, in carrageenan-induced inflammation in the mouse air pouch model. Methods Dried Esenbeckia leiocarpa bark was macerated and extracted resulting in a crude hydroalcoholic extract (CHE) that was partitioned to obtain an alkaloid fraction. The alkaloid was then partitioned in polar and nonpolar subfractions. beta-Sitosterol was isolated from the nonpolar subfraction and identified by comparison with the literature. The effect of beta-sitosterol on 45Ca2+ uptake in activated murine neutrophils, and upon myeloperoxidase and adenosine deaminase activity, IL-1 beta and TNF-a levels in carrageenan-induced inflammation in mice were evaluated. Key findings beta-Sitosterol promoted a time- and dose-dependent increase of the calcium uptake in activated neutrophils that was promptly reversed by nifedipine, BAPTA-AM, LY294002, and colchicine. beta-Sitosterol inhibited myeloperoxidase and adenosine deaminase activity, and IL-1 beta and TNF-a levels. Conclusions beta-Sitosterol inhibited either myeloperoxidase and adenosine deaminase activity or IL-1 beta and TNF-a levels. This effect seemed to be mediated by the calcium uptake in activated neutrophils in a time- and concentration-dependent manner through L-type voltage dependent calcium channels, intracellular calcium, phosphoinositide kinase-3, and microtubule modulation.
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