花生白藜芦醇对埃利希腹水癌体内模型中COX-2的抑制作用

Q4 Pharmacology, Toxicology and Pharmaceutics Current Enzyme Inhibition Pub Date : 2023-07-26 DOI:10.2174/1573408019666230726142647
Hamed A. Abosharaf, Aliaa Habib, Abdul Aziz Gad, Tarek M. Mohamed
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引用次数: 0

摘要

对肿瘤领域感兴趣的研究人员的主要目标仍然是开发一种副作用最小的新型抗癌药物。由于其最小的毒性和令人印象深刻的性能,天然来源介导的抗癌治疗引起了人们的广泛关注。目的:从花生、豆类、豇豆、羽扇豆、蚕豆、大豆等豆科植物中提取纯化白藜芦醇,并评价其对环氧合酶-2 (COX-2)的抑制作用。目的是评价提取白藜芦醇单独或联合阿霉素对埃利希腹水癌(Ehrlich as腹水癌,EAC)模型的抗癌潜力。用硅胶柱提取纯化白藜芦醇。体外研究了提取白藜芦醇对COX-2的抑制作用。然后,根据先前建立的EAC模型评估白藜芦醇单独使用或与阿霉素联合使用的抗增殖作用。研究凋亡/抗凋亡基因和细胞周期阻滞。从花生中提取白藜芦醇后,体外竞争性抑制COX-2,抑制常数(Ki)为0.545µM,与分子对接理论预测值(0.48µM)非常接近。此外,白藜芦醇在体内明显抑制COX-2。重要的是,白藜芦醇能够通过上调Bax和下调抗凋亡基因Bcl-2而引起细胞凋亡,无论是单独使用还是与阿霉素联合使用。此外,白藜芦醇停止细胞周期的能力是其抑制cox -2抗增殖特性的证据。白藜芦醇通过抑制COX-2表现出抗癌潜能,适合体内联合治疗。
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Peanut Resveratrol Inhibits COX-2 in Ehrlich Ascites Carcinoma In vivo Model
The primary goal of researchers interested in the field of oncology continues to be the development of a new anti-cancer medicine with minimal side effects. Due to their minimal toxicity and impressive performance, natural source-mediated anti-cancer treatments are attracting a lot of attention. Objective: The purpose of the current work was to extract and purify resveratrol from local Leguminosae, such as peanut, beans, cowpea, lupine, fava bean, and soybean, and then assess its cyclooxygenase-2 (COX-2) inhibition. The aim was then to evaluate the anticancer potential of extracted resveratrol individually or combined with doxorubicin against Ehrlich ascites carcinoma (EAC) model. Resveratrol was extracted and purified using a silica gel column. The inhibition study of extracted resveratrol was conducted against COX-2 in vitro. Then, the anti-proliferation impact of resveratrol alone or combined with doxorubicin was evaluated against the previously established EAC model. Apoptotic/anti-apoptotic genes and cell cycle arrest were investigated. After being extracted from peanuts, resveratrol inhibited COX-2 in vitro competitively with an inhibition constant (Ki) of 0.545 µM, which is extremely close to the theoretically predicted value (0.48 µM) from molecular docking. Further, resveratrol obviously inhibited COX-2 in vivo. Importantly, resveratrol was able to cause apoptosis by upregulating Bax and downregulating the anti-apoptotic gene Bcl-2, either by itself or in combination with doxorubicin. Additionally, resveratrol's ability to stop the cell cycle is evidence of its COX-2-inhibiting antiproliferative properties. Resveratrol exhibits anticancer potential via inhibition of COX-2, and it could be appropriate for combinational therapy in vivo.
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来源期刊
Current Enzyme Inhibition
Current Enzyme Inhibition Pharmacology, Toxicology and Pharmaceutics-Drug Discovery
CiteScore
1.30
自引率
0.00%
发文量
30
期刊介绍: Current Enzyme Inhibition aims to publish all the latest and outstanding developments in enzyme inhibition studies with regards to the mechanisms of inhibitory processes of enzymes, recognition of active sites, and the discovery of agonists and antagonists, leading to the design and development of new drugs of significant therapeutic value. Each issue contains a series of timely, in-depth reviews written by leaders in the field, covering a range of enzymes that can be exploited for drug development. Current Enzyme Inhibition is an essential journal for every pharmaceutical and medicinal chemist who wishes to have up-to-date knowledge about each and every development in the study of enzyme inhibition.
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