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树叶对大鼠γ射线辐射诱导的肝毒性的影响及其与STING通路和酚类成分的相关性

Impact of Leaves on Gamma Irradiation-Induced Hepatotoxicity in Rats and Correlation with STING Pathway and Phenolic Composition.

作者信息

Selim Nabil M, El-Hawary Seham S, El Zalabani Soheir M, Shamma Rehab Nabil, Mahdy Nariman El Sayed, Sherif Noheir H, Fahmy Hanan A, Mekkawy Mai H, Yasri Abdelaziz, Sobeh Mansour

机构信息

Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 12613, Egypt.

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 12613, Egypt.

出版信息

Pharmaceuticals (Basel). 2020 Oct 19;13(10):320. doi: 10.3390/ph13100320.

DOI:10.3390/ph13100320
PMID:33086669
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7603372/
Abstract

Exposure to ionizing radiation usually results in cellular oxidative damage and may induce liver toxicity. The efficiency of the ethanol extracts of (EWF) and (EWR) leaves in alleviating γ-radiation-induced oxidative hepatotoxicity was herein explored. Proximate and macronutrient composition of the leaves was determined to establish reliable quality control criteria. Colorimetric estimation of total phenolic (TPC) and flavonoid (TFC) contents revealed their occurrence in larger amounts in EWR. In vitro evaluation of the antioxidant capacity by 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and ferric reducing antioxidant power (FRAP) assays confirmed higher efficiency of EWR designating a close correlation with phenolic composition. Four phenolics, viz., naringenin, kaempferol, quercetin, and gallic acid, were isolated from EWR. In vivo assessment of the extracts' antioxidant potential was performed on γ-irradiated (7.5 Gy) female rats. EWR was found more efficient in restoring the elevated liver index, ALT, albumin, cholesterol, and reactive oxygen species (ROS) levels. Both extracts ameliorated the increase in the stimulator of interferon gene (STING) expression. Bioactivity was confirmed by immuno-histochemical examination of inflammatory and apoptotic biomarkers (TNF-α, IL-6 and caspase-3) and histopathological architecture. In addition, the interactions of the isolated compounds with STING were assessed in silico by molecular docking. Therefore, leaves might be suggested as a valuable nutritional supplement to alleviate radiotherapy-induced hepatotoxicity.

摘要

暴露于电离辐射通常会导致细胞氧化损伤,并可能诱发肝毒性。本文探讨了[植物名称1](EWF)和[植物名称2](EWR)叶乙醇提取物在减轻γ辐射诱导的氧化肝毒性方面的效果。测定了叶片的近似成分和大量营养素组成,以建立可靠的质量控制标准。比色法测定总酚(TPC)和类黄酮(TFC)含量表明,它们在EWR中的含量更高。通过2,2-联氮双(3-乙基苯并噻唑啉-6-磺酸)(ABTS)和铁还原抗氧化能力(FRAP)测定法对体外抗氧化能力进行评估,证实EWR的效率更高,这表明其与酚类成分密切相关。从EWR中分离出了四种酚类物质,即柚皮素、山奈酚、槲皮素和没食子酸。对γ照射(7.5 Gy)的雌性大鼠进行了提取物抗氧化潜力的体内评估。发现EWR在恢复升高的肝脏指数、谷丙转氨酶、白蛋白、胆固醇和活性氧(ROS)水平方面更有效。两种提取物均改善了干扰素基因刺激剂(STING)表达的增加。通过对炎症和凋亡生物标志物(TNF-α、IL-6和半胱天冬酶-3)的免疫组织化学检查以及组织病理学结构证实了生物活性。此外,通过分子对接在计算机上评估了分离化合物与STING的相互作用。因此,[植物名称2]叶可能被认为是一种有价值的营养补充剂,可减轻放疗引起的肝毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a22/7603372/72f59ed329d3/pharmaceuticals-13-00320-g008.jpg
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