Acute effect of β-sitosterol on calcium uptake mediates anti-inflammatory effect in murine activated neutrophils

• Published in: Journal of pharmacy and pharmacology Vol. 65; no. 1; p. 115
• Main Authors: Liz, Rafael, Zanatta, Leila, dos Reis, Gustavo Oliveira, Horst, Heros, Pizzolatti, Moacir Geraldo, Silva, Fátima Regina Mena Barreto, Fröde, Tânia Silvia
• Format: Journal Article
• Language: English
• Published: England 01.01.2013
• Subjects: Adenosine Deaminase - blood; Adenosine Deaminase - chemistry; Adenosine Deaminase - metabolism; Adenosine Deaminase Inhibitors - administration & dosage; Adenosine Deaminase Inhibitors - pharmacology; Adenosine Deaminase Inhibitors - therapeutic use; Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Calcium Channel Blockers - pharmacology; Calcium Channels, L-Type - chemistry; Calcium Channels, L-Type - metabolism; Calcium Signaling - drug effects; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Hypolipidemic Agents - administration & dosage; Hypolipidemic Agents - pharmacology; Hypolipidemic Agents - therapeutic use; Injections, Intraperitoneal; Interleukin-1beta - antagonists & inhibitors; Interleukin-1beta - blood; Interleukin-1beta - metabolism; Mice; Microtubules - drug effects; Microtubules - metabolism; Neutrophil Activation - drug effects; Neutrophils - drug effects; Neutrophils - immunology; Neutrophils - metabolism; Peroxidase - antagonists & inhibitors; Peroxidase - blood; Peroxidase - metabolism; Phosphatidylinositol 3-Kinase - antagonists & inhibitors; Phosphatidylinositol 3-Kinase - metabolism; Pleurisy - immunology; Pleurisy - metabolism; Pleurisy - prevention & control; Sitosterols - administration & dosage; Sitosterols - pharmacology; Sitosterols - therapeutic use; Tubulin Modulators - pharmacology; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - metabolism
• DOI: 10.1111/j.2042-7158.2012.01568.x

To evaluate the effect of β-sitosterol on ⁴⁵Ca²⁺ uptake in activated murine neutrophils, and upon myeloperoxidase and adenosine deaminase activity, and interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) levels, in carrageenan-induced inflammation in the mouse air pouch model. 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. β-Sitosterol was isolated from the nonpolar subfraction and identified by comparison with the literature. The effect of β-sitosterol on ⁴⁵Ca²⁺ uptake in activated murine neutrophils, and upon myeloperoxidase and adenosine deaminase activity, IL-1β and TNF-α levels in carrageenan-induced inflammation in mice were evaluated. β-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. β-Sitosterol inhibited myeloperoxidase and adenosine deaminase activity, and IL-1β and TNF-α levels. β-Sitosterol inhibited either myeloperoxidase and adenosine deaminase activity or IL-1β and TNF-α 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.