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黄酮醇(Flavocoxid),一种环氧化酶-2和5-脂氧合酶的双重抑制剂,在缺血性中风大鼠模型中表现出神经保护作用。

Flavocoxid, dual inhibitor of cyclooxygenase-2 and 5-lipoxygenase, exhibits neuroprotection in rat model of ischaemic stroke.

作者信息

Singh Dhirendra Pratap, Chopra Kanwaljit

机构信息

Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Centre of Advance Studies, Panjab University, Chandigarh 160014, India.

Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Centre of Advance Studies, Panjab University, Chandigarh 160014, India.

出版信息

Pharmacol Biochem Behav. 2014 May;120:33-42. doi: 10.1016/j.pbb.2014.02.006. Epub 2014 Feb 18.

Abstract

The efficacy of flavocoxid, a prescription medical food used in osteoarthritis in the USA, containing natural flavonoids, baicalin and catechin in experimentally induced cerebral ischaemia in rats was evaluated. Rationale behind the study was that the transient acute ischaemic attack triggers neuroinflammatory cascade. Global cerebral ischaemia was induced transiently by occluding both common carotid arteries for 15 min followed by restoration of perfusion. Flavocoxid (50, 100, 200mg/kg; p.o.) pre-treatment was instituted 6 days prior to surgery and fluoxetine (10mg/kg, p.o.) and rivastigmine (2mg/kg, p.o.) as a standard treatment for depression and cognition impairment was implied from day 1 after the surgery. Different behavioural, biochemical, neurochemical tests, molecular markers of inflammation e.g. tumour necrosis factor-α, interleukin-1 beta, and nuclear factor-kappa B levels and infarct volume were determined. Flavocoxid's strong antioxidant properties figured out from the decreased level of lipid peroxidation and protection of endogenous antioxidants like reduced glutathione and superoxide dismutase. It also reduced TNF-α, IL-1β, and NF-κB levels, and infarct volume as well as protected the loss of biogenic amines in brain tissue of ischaemic rats. This dual inhibitor of cyclooxygenase-1 and 2 with additional 5-lipoxygenase inhibition activity might be useful as a potential neuroprotectant medical food in ischaemic stroke prone patient population.

摘要

在美国,一种用于骨关节炎的处方医用食品——黄烷醇氧化合物,含有天然黄酮类化合物、黄芩苷和儿茶素,其在大鼠实验性脑缺血中的疗效得到了评估。该研究的理论依据是短暂性急性缺血性发作会引发神经炎症级联反应。通过阻断双侧颈总动脉15分钟,随后恢复灌注,短暂诱导全脑缺血。在手术前6天开始进行黄烷醇氧化合物(50、100、200毫克/千克;口服)预处理,从手术后第1天起使用氟西汀(10毫克/千克,口服)和卡巴拉汀(2毫克/千克,口服)作为抑郁症和认知障碍的标准治疗药物。测定了不同的行为、生化、神经化学测试、炎症分子标志物,如肿瘤坏死因子-α、白细胞介素-1β和核因子-κB水平以及梗死体积。黄烷醇氧化合物强大的抗氧化特性表现为脂质过氧化水平降低以及对内源性抗氧化剂如还原型谷胱甘肽和超氧化物歧化酶的保护。它还降低了肿瘤坏死因子-α、白细胞介素-1β和核因子-κB水平以及梗死体积,并保护了缺血大鼠脑组织中生物胺的损失。这种兼具环氧化酶-1和2双重抑制作用以及额外的5-脂氧合酶抑制活性的物质,可能作为一种潜在的神经保护医用食品,对易患缺血性中风的患者群体有用。

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