从伊朗特有植物蜂斗菜中提取和鉴定两种类黄酮：槲皮素对谷胱甘肽过氧化物酶激活作用及对胆管结扎大鼠羟脯氨酸和蛋白氧化的改善。

Extraction and Identification of Two Flavonoids in Phlomoides hyoscyamoides as an Endemic Plant of Iran: The Role of Quercetin in the Activation of the Glutathione Peroxidase, the Improvement of the Hydroxyproline and Protein Oxidation in Bile Duct-Ligated Rats.

机构信息

Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran

Department of Clinical Biochemistry, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran

出版信息

Curr Comput Aided Drug Des. 2020;16(5):629-640. doi: 10.2174/1573409915666190903163335.

DOI:10.2174/1573409915666190903163335

PMID:31481005

Abstract

BACKGROUND

Cholestatic liver disease, a serious chronic condition that develops progressive hepatic degeneration through free radicals.

OBJECTIVE

The present study was designed to extract and identify two flavonoids in Phlomoides hyoscyamoides plant, native to Iran and evaluate the role of quercetin identified on the liver injury among bile ductligated rats.

METHODS

This study was conducted on 25 male Wistar rats within three groups of sham control, mere bile duct-ligated, and bile duct-ligated with quercetin. The bile duct-ligated animals received quercetin at a dose of 50 mg/kg/day for 10 days, followed by biochemical tests, oxidative stress markers, activity of antioxidant enzymes and hematoxylin and eosin staining. Molecular docking was used to explore the interactive behavior of quercetin with glutathione peroxidase.

RESULTS

According to analyses of the obtained extract, two main active ingredients of P. hyoscyamoides were rutin and quercetin. Bile duct-ligated group showed a significant liver necrosis, a clear increase in plasma and tissue oxidative stress parameters, and a decrease in glutathione peroxidase activity as compared to sham control group. Quercetin injection in bile duct-ligated rats resulted in significant decrease in hydroxyproline, protein carbonyl and histopathologic indexes and significant increase in glutathione peroxidase activity (P-value≤0.05). Based on the molecular docking, the quercetin was able to regulate the glutathione peroxidase activity.

CONCLUSION

The quercetin acts as an enzyme inducer by renewing the glutathione peroxidase activity and inhibiting the oxidation of proteins and hence decreases the oxidative stress. These results could be a sign of confirming the positive role of quercetin in attenuating the liver damage and degeneration.

摘要

背景

胆汁淤积性肝病是一种严重的慢性疾病，通过自由基导致进行性肝退化。

目的

本研究旨在从伊朗本土植物 Phlomoides hyoscyamoides 中提取并鉴定两种类黄酮，并评估鉴定出的类黄酮 quercetin 在胆管结扎大鼠肝损伤中的作用。

方法

本研究共纳入 25 只雄性 Wistar 大鼠，分为假手术对照组、单纯胆管结扎组和胆管结扎加 quercetin 组。胆管结扎动物每日给予 quercetin 50mg/kg 共 10 天，随后进行生化测试、氧化应激标志物、抗氧化酶活性和苏木精-伊红染色。采用分子对接研究 quercetin 与谷胱甘肽过氧化物酶的相互作用行为。

结果

根据提取物分析，P. hyoscyamoides 的两种主要活性成分是芦丁和 quercetin。与假手术对照组相比，胆管结扎组出现明显的肝坏死，血浆和组织氧化应激参数明显增加，谷胱甘肽过氧化物酶活性降低。与胆管结扎组相比，胆管结扎大鼠注射 quercetin 后羟脯氨酸、蛋白羰基和组织学指标显著降低，谷胱甘肽过氧化物酶活性显著升高（P 值≤0.05）。基于分子对接，quercetin 能够调节谷胱甘肽过氧化物酶的活性。