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莽草酸对过氧化氢诱导的氧化应激的体外神经保护作用

In Vitro Neuroprotective Effect of Shikimic Acid Against Hydrogen Peroxide-Induced Oxidative Stress.

作者信息

Rabelo Thallita Kelly, Zeidán-Chuliá Fares, Caregnato Fernanda Freitas, Schnorr Carlos Eduardo, Gasparotto Juciano, Serafini Mairim Russo, de Souza Araújo Adriano Antunes, Quintans-Junior Lucindo José, Moreira José Cláudio Fonseca, Gelain Daniel Pens

机构信息

Center of Oxidative Stress Research (CEEO), Department of Biochemistry, Federal University of Rio Grande do Sul (UFRGS), 2600, Ramiro Barcelos Street - Annex, CEP 90035-003, Porto Alegre, RS, Brazil.

Laboratory of Pharmaceutical Assays and Toxicity, Federal University of Sergipe (LeFT/UFS), São Cristóvão, SE, Brazil.

出版信息

J Mol Neurosci. 2015 Aug;56(4):956-965. doi: 10.1007/s12031-015-0559-9. Epub 2015 Apr 11.

Abstract

Shikimic acid (SA), originally extracted from Illicium verum Hook. fil., is an indispensable starting material for the synthesis of the antiviral drug Oseltamivir (Tamiflu(®)) with very limited number of studies regarding its biological effects in vitro. Therefore, we here evaluated the thermoanalytical profile, redox properties, and in vitro effects of SA on human neuronal-like cells (SH-SY5Y). The thermoanalytical profile of SA was studied by using differential scanning calorimetry (DSC) and thermogravimetry/derivative thermogravimetry (TG/DTG) characterization. Both antioxidant potential and in vitro lipoperoxidation levels were analyzed. Cell viability and intracellular reactive species (RS) production was determined by DCF and SRB assays, respectively. Our results show in vitro antioxidant activity of SA without exerting cytotoxic effects on SH-SY5Y cells at tested concentrations of 10 nM, 10 μM, and 10 mM. In addition, SA protected the cells against H2O2-induced toxicity; effect that could be related, at least in part, with decreased intracellular RS production and its antioxidant potential. The present study shows evidence for neuroprotective actions of SA against oxidative stress-induced toxicity on SH-SY5Y cells, inviting for further investigation about its potential use in the context of oxidative stress-associated neurodegenerative diseases.

摘要

莽草酸(SA)最初是从八角茴香中提取的,它是合成抗病毒药物奥司他韦(达菲®)不可或缺的起始原料,但关于其体外生物学效应的研究非常有限。因此,我们在此评估了SA的热分析图谱、氧化还原特性以及对人神经样细胞(SH-SY5Y)的体外作用。通过差示扫描量热法(DSC)和热重/微商热重法(TG/DTG)表征研究了SA的热分析图谱。分析了抗氧化潜力和体外脂质过氧化水平。分别通过DCF和SRB测定法测定细胞活力和细胞内活性物质(RS)的产生。我们的结果表明,在10 nM、10 μM和10 mM的测试浓度下,SA具有体外抗氧化活性,且对SH-SY5Y细胞无细胞毒性作用。此外,SA保护细胞免受H2O2诱导的毒性;这种作用至少部分可能与细胞内RS产生减少及其抗氧化潜力有关。本研究表明,SA对SH-SY5Y细胞氧化应激诱导的毒性具有神经保护作用,这促使人们进一步研究其在氧化应激相关神经退行性疾病中的潜在用途。

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