In vitro effects of mangiferin on superoxide concentrations and expression of the inducible nitric oxide synthase, tumour necrosis factor-alpha and transforming growth factor-beta genes.
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-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 10U/mL of interferon-gamma were evaluated semiquantitatively by the retrotranscriptase-polymerase chain reaction. MA at 10-100 microM, like the known O(2)(-) scavenger superoxide dismutase (1U/mL), scavenged O(2)(-) produced by the HX/XO and PMS-NADH systems. By contrast MA at 1-100 microM, unlike allopurinol (10 microM), was unable to inhibit XO activity. MA at 1-100 microM did not modify resting tone or the contractile responses elicited by 1 microM phenylephrine or 1 microM phorbol 12-myristate 13-acetate in rat aorta. MA at 1-100 microM, like dexamethasone (100 microM), decreased iNOS mRNA levels in activated macrophages. At 100 microM, 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-alpha 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.
Leiro
José Manuel
JM
Departamento de Microbiología y Parasitología, Universidad de Santiago de Compostela, Spain. mpleiro@usc.es
Alvarez
Ezequiel
E
Arranz
Juan Alberto
JA
Siso
Isabel González
IG
Orallo
Francisco
F
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology; D008297:Male; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013481:Superoxides / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000235:genetics*; D014966:Xanthenes / Q000494:pharmacology*; D044004:Xanthones
D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D014966:Xanthenes; D044004:Xanthones; D013481:Superoxides; C013592:mangiferin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat