从洋蓟花中提取的酚类化合物对α-葡萄糖苷酶、丁酰胆碱酯酶和乙酰胆碱酯酶的抑制活性:硅学和体外研究

IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Jawaher A.M. Alotaibi , Alaa Sirwi , Ali M. El-Halawany , Ahmed Esmat , Gamal A. Mohamed , Sabrin R.M. Ibrahim , Abdulrahim A. Alzain , Taher F. Halawa , Martin Safo , Hossam M. Abdallah
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引用次数: 0

摘要

通过对马齿苋花进行化学研究,分离出了七种代谢物,分别是:对羟基苯甲酸(1)、反式羟基肉桂酸(2)、山奈酚-6-C-葡萄糖苷(3)、黄芪苷(4)、软骨素(5)、山奈酚-3-O-芸香糖苷(6)和山奈酚-3-O-槐糖苷(7)。对分离出的化合物进行了针对人体肠道α-葡萄糖苷酶、乙酰胆碱酯酶和丁酰胆碱酯酶的虚拟筛选。此外,还评估了生物活性化合物的抗氧化活性。与多奈哌齐(-83.33 千卡/摩尔)相比,化合物 1 和 5 与乙酰胆碱酯酶的结合亲和力适中(结合能分别为-5.33 和-4.18 千卡/摩尔)。化合物 1-7 与丁酰胆碱酯酶的亲和力较弱。与阿卡波糖(参比化合物)相比,化合物 2 和 4 与人肠道 α-葡萄糖苷酶的结合亲和力适中,而化合物 2 的亲和力较低。分子动力学研究表明,在 100 毫微秒的模拟时间内,化合物 4 与结合位点形成了稳定的复合物。体外实验结果与虚拟实验结果一致,化合物 1 和 5 对乙酰胆碱酯酶有轻微的抑制作用(IC50 分别为 150.6 和 168.7 µM)。化合物 4 对α-葡萄糖苷酶有中度抑制作用,IC50 为 93.71 µM。这些生物活性化合物还在 ABTS [2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)] 、ORAC(氧自由基吸收能力)和金属螯合试验中表现出显著的抗氧化活性,表明它们具有改善阿尔茨海默病(AD)痴呆症和缓解高血糖的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
α-Glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from Carthamus tinctorius L. flowers: In silico and in vitro studies

Chemical investigation of Carthamus tinctorius L. flowers resulted in isolation of seven metabolites that were identified as; p-Hydroxybenzoic acid (1), trans hydroxy cinnamic acid (2), kaempferol-6-C-glucoside (3), astragalin (4), cartormin (5), kaempferol-3-O-rutinoside (6), and kaempferol–3-O-sophoroside (7). Virtual screening of the isolated compounds against human intestinal α-glucosidase, acetylcholinesterase, and butyrylcholinesterase was carried out. Additionally, the antioxidant activity of the bioactive compounds was assessed. Compounds 1 and 5 exhibited moderate binding affinities to acetylcholinesterase (binding energy −5.33 and −4.18 kcal/mol, respectively), compared to donepezil (-83.33kcal/mol). Compounds 17 demonstrated weak affinity to butyrylcholinesterase. Compounds 2 and 4 displayed moderate binding affinity to human intestinal α-glucosidase,compared to Acarbose (reference compound), meanwhile compound 2 exhibited lower affinity. Molecular dynamic studies revealed that compound 4 formed a stable complex with the binding site throughout a 100 ns simulation period. The in-vitro results were consistent with the virtual experimental results, as compounds 1 and 5 showed mild inhibitory effects on acetylcholinesterase (IC50s 150.6 and 168.7 µM, respectively). Compound 4 exhibited moderate α-glucosidase inhibition with an IC50 of 93.71 µM. The bioactive compounds also demonstrated notable antioxidant activity in ABTS [2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)], ORAC (oxygen radical-absorbance capacity), and metal chelation assays, suggesting their potential in improving dementia in Alzheimer’s disease (AD) and mitigating hyperglycemia.

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来源期刊
Saudi Pharmaceutical Journal
Saudi Pharmaceutical Journal PHARMACOLOGY & PHARMACY-
CiteScore
6.10
自引率
2.40%
发文量
194
审稿时长
67 days
期刊介绍: The Saudi Pharmaceutical Journal (SPJ) is the official journal of the Saudi Pharmaceutical Society (SPS) publishing high quality clinically oriented submissions which encompass the various disciplines of pharmaceutical sciences and related subjects. SPJ publishes 8 issues per year by the Saudi Pharmaceutical Society, with the cooperation of the College of Pharmacy, King Saud University.
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