Pinitol inhibits LPS-induced inflammatory response in murine peritoneal macrophages:

Role of NFÒš-B signaling pathway.

N.H Gonzalez-Mauraza, M. Sanchez-Hidalgo, M. Aparicio-Soto, A. Leon-Gonzalez, A. Cardeno, C. Alarcon de la Lastra, C. Martin-Cordero. Facultad de Farmacia se la Universidad de Sevilla, Farmacologia-41012, Spain

Introduction: D-Pinitol (3-O-methyl-chiroinositol) is a natural, sugar-like molecule found in a variety of plant foods including legumes. It has been shown to exhibit antidiabetic, antioxidative and anti-inflammatory activities through undefined mechanisms. Aim: Thus, in the present study, we investigated the effects of pinitol (12.5, 25, 50 and 100 µM) on LPS-stimulated inflammatory response in murine peritoneal macrophages and deep insight into action mechanism involved in its anti-inflammatory effect [1]. Material and Methods: Cell viability was determined using sulphorhodamine (SRB) assay. Antioxidant activity was measured by DPPH free radical scavenging method and nitric oxide (NO) production was assayed using the Griess reaction. Moreover, the protein expression of cyclooxygenase (COX)-2 and the inducible synthase nitric oxide (iNOS) as well as the role of the nuclear transcription factor kappa B (NFÒšB) signalling pathway was determined by Western blot. Results: LPS-induced inflammatory response was characterized by an increase in NO production and an upregulation of COX-2 and iNOS protein expressions followed by a remarkable decrease in NF-kB-inhibitory protein (Iκβα). On the contrary, pinitol (at µM range) exerted anti-inflammatory effect inhibiting LPS-induced nitrites production in murine peritoneal macrophages (25µM:68.7±0.5% p<0.01; 50µM:53.3±0.9% p<0.001; 100µM:17.6±0.9% p<0.001) and decreasing the proinflammatory COX-2 (100µM:16.8±0.02% p<0.01). and iNOS (50µM:41.7±0.2% p<0.05; 100µM:0.1±0.1% p<0.001) protein expressions without affecting cellular viability. In addition, pinitol prevented the inhibitory kappa B alpha protein (IκBα) degradation (100 µM:169.3±0.1% p<0.01). Conclusion: Pinitol inhibits LPS-induced inflammatory response in murine peritoneal macrophages through NFÒšB signalling pathway suggesting that it may be an attractive therapeutic strategy for the management of inflammatory diseases. References: [1] De la Puerta R, Marquez-Martin A, Fernandez-Arche A, Ruiz-Gutierrez V. Influence of dietary fat on oxidative stress and inflammation in murine macrophages. Nutrition. 2009. (5): 548-54.