Protection against septic shock and suppression of tumor necrosis factor alpha and nitric oxide production on macrophages and microglia by a standard aqueous extract of Mangifera indica L. (VIMANG®) -: Role of mangiferin isolated from the extract

The present study illustrates the effects of a standard aqueous extract, used in Cuba under the brand name of VIMANG(R), from the stem bark of Mangifera indica L. on the production of tumor necrosis factor alpha (TNFalpha) and nitric oxide (NO) in in vivo and in vitro experiments. In vivo was determined by the action of the extract and its purified glucosylxanthone (mangiferin) on TNFalpha in a murine model of endotoxic shock using Balb/c mice pre-treated with lipopolysaccharide (LPS) 0.125 mg kg(-1), i.p. In vitro, M. indica extract and mangiferin were tested on TNFalpha and NO production in activated macrophages (RAW264.7 cell line) and microglia (N9 cell line) stimulated with LPS (10 ng ml(-1)) and interferon gamma (IFNgamma, 2 U ml(-1)). M. indica extract reduced dose-dependently TNFalpha production in the serum (ED50 64.5 mg kg(-1)) and the TNFalpha mRNA expression in the lungs and livers of mice. Mangiferin also inhibited systemic TNFalpha at 20 mg kg(-1). In RAW264.7, the extract inhibited TNFalpha (IC50 = 94.1 mug ml(-1)) and NO (IC50 = 64.4 mug ml(-1)). In microglia the inhibitions of the extract were IC50 = 76.0 mug ml(-1) (TNFalpha) and 84.0 mug ml(-1) (NO). These findings suggest that the anti-inflammatory response observed during treatment with M. indica extract must be related with inhibition of TNFalpha and NO production. Mangiferin, a main component in the extract, is involved in these effects. The TNFalpha and NO inhibitions by M. indica extract and mangiferin on endotoxic shock and microglia are reported here for the first time. (C) 2004 Elsevier Ltd. All rights reserved.