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
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
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DOI：
10.1016/s0006-2952(03)00041-8
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发表时间：
2003-04-15
影响因子：
5.8
通讯作者：
Orallo, F
中科院分区：
文献类型：
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作者：
Leiro, JM;Alvarez, E;Orallo, F
本研究调查了天然多酚芒果苷 (MA) 对超氧阴离子 (02) 产生、黄嘌呤氧化酶 (XO) 活性、血管收缩性、诱导型一氧化氮合酶 (iNOS) mRNA 水平、坏死因子-α (TNF-α) mRNA 水平和肿瘤生长因子-β (TGF-β) mRNA 水平的影响。 O-2(-) 由次黄嘌呤-黄嘌呤氧化酶 (HX-XO) 和吩嗪硫酸甲酯 (PMS)-NADH 系统产生。 XO 活性通过以黄嘌呤为底物测量尿酸产生来确定。用完整的大鼠主动脉环进行血管收缩实验。通过逆转录酶-聚合酶链反应半定量评估体内用 3% 硫代乙醇酸盐刺激的大鼠巨噬细胞和体外用 100 ng/mL 脂多糖和 10 U/mL 干扰素-γ 刺激的大鼠巨噬细胞中的 iNOS、TNF-α 和 TGF-β 基因表达。 MA 浓度为 10-100 muM，与已知的 O-2(-) 清除剂超氧化物歧化酶 (1 U/mL) 一样，清除 O-2(-) 由 HX/XO 和 PMS-NADH 系统产生。相比之下，1-100 muM 的 MA 与别嘌呤醇 (10 muM) 不同，无法抑制 XO 活性。 1-100 μM 的 MA 不会改变大鼠主动脉中 1 μM 去氧肾上腺素或 1 μM 佛波醇 12-肉豆蔻酸酯 13-乙酸酯引起的静息张力或收缩反应。 1-100 muM 的 MA 与地塞米松 (100 AM) 一样，可降低活化巨噬细胞中的 iNOS mRNA 水平。 100 muM 时，MA 还降低了 TNF-α mRNA 水平，但增加了 TGF-β mRNA 水平。因此，这些结果表明MA是一种O-2(-)清除剂，并且它抑制iNOS和TNF-α基因的表达，表明它在治疗炎症和/或神经退行性疾病方面可能具有潜在价值。此外，MA 增强 TGF-β 基因表达的发现表明，这种多酚在预防癌症、自身免疫性疾病、动脉粥样硬化和冠心病方面也可能具有价值。 (C) 2003 Elsevier Science Inc. 保留所有权利。
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.