槲皮素的抗镰状红细胞作用可能与人镰状红细胞中脱氧血红蛋白、2,3 -二磷酸甘油变异酶、氧化还原稳态和功能化学改变的调节有关。

A. Muhammad, A. Waziri, G. E. Forcados, B. Sanusi, H. Sani, I. Malami, I. Abubakar, Musa Fatima Abbah, A. T. Nelson, B. Musa, H. Mohammed
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引用次数: 4

摘要

现在,镰状细胞贫血仍然是非洲人最主要的近交系血红蛋白病之一。本研究在支持预防和治疗方法的同时,利用硅和体外模型研究了槲皮素通过调节脱氧血红蛋白、氧化还原稳态和改变人镰状红细胞功能化学来抗镰状红细胞的作用。槲皮素与脱氧血红蛋白和2,3 -二磷酸甘油酸突变酶对接,通过强疏水和氢键作用,其催化位点结合能分别为- 30.427和- 21.106 kcal/mol, Ki分别为0.988μM和0.992μM。用2%的焦亚硫酸盐在3h诱导镰状细胞。槲皮素浓度为5.0μg/mL时,能显著抑制镰状细胞的生长;浓度为7.5μg/mL时,能显著抑制镰状细胞生长,分别为83.6%和75.9%。槲皮素还显著(P<0.05)维持了红细胞膜的完整性,从观察到的溶血率来看,槲皮素明显高于未治疗组。槲皮素显著(P<0.05)预防和抑制脂质过氧化,同时刺激GSH和CAT水平显著(P<0.05)升高,SOD水平显著(P<0.05)降低。从我们的FTIR结果来看,相对于诱导红细胞/未处理红细胞,在功能化学方面的变化(弯曲和拉伸)和官能团方面观察到有利的变化。因此,槲皮素的抗镰状细胞效应可能与人镰状红细胞中脱氧血红蛋白、氧化还原稳态和功能化学改变的调节有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Antisickling Effects of Quercetin may be Associated with Modulation of Deoxyhaemoglobin, 2, 3-bisphosphoglycerate mutase, Redox Homeostasis and Alteration of Functional Chemistry in Human Sickle Erythrocytes.
Abstract It is now glaring that sickle cell anaemia is still one of the highest leading inbred hemoglobinopathy amongst Africans. This study examined the antisickling effects of quercetin via modulation of deoxy-haemoglobin, redox homeostasis and alteration of functional chemistry in human sickle erythrocyte using in silico and in vitro models while espousing preventive and curative approaches. Quercetin was docked against deoxy-haemoglobin and 2, 3-bisphosphoglycerate mutase, with binding energies (−30.427 and −21.106 kcal/mol) and Ki of 0.988μM and 0.992μM at their catalytic sites via strong hydrophobic and hydrogen bond interactions. Induction of sickling was done using 2% metabisulphite at 3h. Treatment with quercetin prevented sickling outstandingly at 5.0μg/mL and reversed same at 7.5μg/mL, 83.6% and 75.9%, respectively. Quercetin also significantly (P<0.05) maintained the integrity of erythrocyte membrane apparently from the observed % haemolysis relative to untreated. Quercetin significantly (P<0.05) prevented and counteracted lipid peroxidation while stimulating GSH and CAT levels which were detected to considerably (P<0.05) increase with simultaneous significant (P<0.05) reduction in SOD level based on curative approach. Umpiring from our FTIR results, a favorable alteration in the part of functional chemistry in terms of shifts (bend and stretches) and functional groups were observed relative to the induced erythrocyte/untreated. Thus, antisickling effects of quercetin may be associated with modulation of deoxy-haemoglobin, redox homeostasis and alteration of functional chemistry in human sickle erythrocytes.
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