Protective effects of the secondary metabolites from Quercus salicina Blume against gentamicin-induced nephrotoxicity in zebrafish (Danio rerio) model

IF 3.9 3区 环境科学与生态学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Comparative Biochemistry and Physiology C-toxicology & Pharmacology Pub Date : 2024-06-08 DOI:10.1016/j.cbpc.2024.109952
Shuang-Hui Yin , Wen-Jun Zhang , Lu-Lu Jiang , Guang-Yue Wang , You-Jin Jeon , Yuling Ding , Yong Li
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Abstract

To reveal the protective effect on the nephrotoxicity of Quercus salicina Blume(QS), a traditional medicine for the treatment of urolithiasis, the 50 % ethanol extract from the branches and leaves of QS was chemically studied by systematic solvent extraction and HPLC chromatography. Two phenolic acids and three flavonoids were identified by nuclear magnetic resonance spectroscopy, namely Ferulic acid (1), p-Hydroxycinnamic acid (2), Hesperidin (3), Formononetin (4), and Quercetin (5). At the same time, the gentamicin-induced nephrotoxicity of zebrafish was used as a model for the first time. The antioxidant activity of these derivatives with good antioxidant activity screened from free radical scavenging experiments in vitro (DPPH and ABTS) was evaluated in vivo, including protein levels (LPO, NO, GSH, and SOD), kidney injury factor (KIM-1), zebrafish kidney pathology and real-time PCR. The results showed that metabolites 1, 3, and 5 had strong antioxidant activity, and oxidative stress in renal tissue was significantly reduced; KIM-1, TNF-α, and IL-6 mRNA expression in a dose-dependent manner, which preliminarily revealed the protective effect of the secondary metabolites of QS on nephrotoxicity, and preliminarily discussed the structure-activity relationship. This study provides an experimental basis for further exploring the mechanism of QS in the kidney.

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柞树次生代谢物对斑马鱼(Danio rerio)模型中庆大霉素诱导的肾毒性的保护作用。
为了揭示治疗泌尿系结石的传统药物槲寄生(Quercus salicina Blume,QS)对肾毒性的保护作用,采用系统溶剂萃取和高效液相色谱法对槲寄生枝叶的50%乙醇提取物进行了化学研究。通过核磁共振光谱鉴定出两种酚酸和三种黄酮类化合物,即阿魏酸(1)、对羟基肉桂酸(2)、橙皮甙(3)、甲羧黄酮(4)和槲皮素(5)。同时,首次以庆大霉素诱导的斑马鱼肾毒性为模型。对这些在体外自由基清除实验(DPPH 和 ABTS)中筛选出的具有良好抗氧化活性的衍生物的抗氧化活性进行了体内评估,包括蛋白质水平(LPO、NO、GSH 和 SOD)、肾损伤因子(KIM-1)、斑马鱼肾脏病理学和实时 PCR。结果表明,代谢物1、3和5具有较强的抗氧化活性,肾组织氧化应激明显降低;KIM-1、TNF-α和IL-6 mRNA的表达呈剂量依赖性,初步揭示了QS次生代谢物对肾毒性的保护作用,并初步探讨了其结构-活性关系。该研究为进一步探讨 QS 在肾脏中的作用机制提供了实验依据。
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来源期刊
CiteScore
7.50
自引率
5.10%
发文量
206
审稿时长
30 days
期刊介绍: Part C: Toxicology and Pharmacology. This journal is concerned with chemical and drug action at different levels of organization, biotransformation of xenobiotics, mechanisms of toxicity, including reactive oxygen species and carcinogenesis, endocrine disruptors, natural products chemistry, and signal transduction with a molecular approach to these fields.
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