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

• Published in: Biochemical pharmacology 2003-04, Vol.65 (8), p.1361-1371
• Main Authors: Leiro, José Manuel, Álvarez, Ezequiel, Arranz, Juan Alberto, Siso, Isabel González, Orallo, Francisco
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cytokines; Gene Expression Regulation - drug effects; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - physiology; Male; Mangiferin; Medical sciences; mRNA levels; Nitric oxide; Nitric Oxide Synthase - drug effects; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type II; Peritoneal macrophages; Rat; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Superoxide anion; Superoxides - metabolism; Transforming Growth Factor beta - drug effects; Transforming Growth Factor beta - genetics; Tumor Necrosis Factor-alpha - drug effects; Tumor Necrosis Factor-alpha - genetics; Xanthenes - pharmacology; Xanthones
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/S0006-2952(03)00041-8

This study investigated the effects of the natural polyphenol mangiferin (MA) on superoxide anion (O 2 −) production, xanthine oxidase (XO) activity, vascular contractility, inducible nitric oxide synthase (iNOS) mRNA levels, tumour necrosis factor-alpha (TNF-α) mRNA levels, and tumour growth factor-beta (TGF-β) 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-α and TGF-β 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 μM, 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 μM, unlike allopurinol (10 μM), was unable to inhibit XO activity. MA at 1–100 μM did not modify resting tone or the contractile responses elicited by 1 μM phenylephrine or 1 μM phorbol 12-myristate 13-acetate in rat aorta. MA at 1–100 μM, like dexamethasone (100 μM), decreased iNOS mRNA levels in activated macrophages. At 100 μM, MA also reduced TNF-α mRNA levels, but increased TGF-β mRNA levels. These results thus indicate that MA is an O 2 − scavenger and that it inhibits expression of the iNOS and TNF-α 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-β gene expression suggests that this polyphenol might also be of value in the prevention of cancer, autoimmune disorders, atherosclerosis and coronary heart disease.