In vitro effects of mangiferin on superoxide concentrations and expression of the inducible nitric oxide synthase, tumour necrosis factor-α and transforming growth factor-β genes

This study investigated the effects of the natural polyphenol mangiferin (MA) on superoxide anion (02) production, xanthine oxidase (XO) activity, vascular contractility, inducible nitric oxide synthase (iNOS) mRNA levels, turnout necrosis factor-alpha (TNF-alpha) mRNA levels, and tumour growth factor-beta (TGF-beta) mRNA levels. O-2(-) was generated by the hypoxanthine-xanthine oxidase (HX-XO) and phenazine methosulphate (PMS)-NADH systems. XO activity was determined by measurement of uric acid production with xanthine as substrate. Vascular contraction experiments were performed with intact rat aortic rings. iNOS, TNF-alpha and TGF-beta gene expression in rat macrophages stimulated in vivo with 3% thioglycollate and in vitro with 100 ng/mL lipopolysaccharide and 10 U/mL of interferon-gamma were evaluated semiquantitatively by the retrotranscriptase-polymerase chain reaction. MA at 10-100 muM, like the known O-2(-) scavenger superoxide dismutase (1 U/mL), scavenged O-2(-) Produced by the HX/XO and PMS-NADH systems. By contrast MA at 1-100 muM, unlike allopurinol (10 muM), was unable to inhibit XO activity. MA at 1-100 muM did not modify resting tone or the contractile responses elicited by 1 muM phenylephrine or 1 muM phorbol 12-myristate 13-acetate in rat aorta. MA at 1-100 muM, like dexamethasone (100 AM), decreased iNOS mRNA levels in activated macrophages. At 100 muM, MA also reduced TNF-alpha mRNA levels, but increased TGF-beta mRNA levels. These results thus indicate that MA is an O-2(-) scavenger and that it inhibits expression of the iNOS and TNF-a genes, suggesting that it may be of potential value in the treatment of inflammatory and/or neurodegenerative disorders. In addition, the finding that MA enhances TGF-beta gene expression suggests that this polyphenol might also be of value in the prevention of cancer, autoimmune disorders, atherosclerosis and coronary heart disease. (C) 2003 Elsevier Science Inc. All rights reserved.