Crocus sativus Extract Tightens the Blood-Brain Barrier, Reduces Amyloid β Load and Related Toxicity in 5XFAD Mice.

Crocus sativus Extract Tightens the Blood-Brain Barrier, Reduces Amyloid β Load and Related Toxicity in 5XFAD Mice.
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DOI:
10.1021/acschemneuro.7b00101
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发表时间:
2017-08-16
影响因子:
5
通讯作者:
Kaddoumi A
Kaddoumi A
中科院分区:
医学3区
文献类型:
--
作者:
Batarseh YS;Bharate SS;Kumar V;Kumar A;Vishwakarma RA;Bharate SB;Kaddoumi A

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番红花,通常被称为阿育吠陀或Kesar,用于阿育吠陀和其他民间药物的各种目的,作为春药,解痉药和祛痰药。以前的证据表明,番红花与改善阿尔茨海默病(AD)患者的认知功能有关。本研究的目的是在体外和体内研究西红花发挥其积极作用的机制。评价番红花提取物对Aβ负荷的影响及相关毒性。体外结果表明,番红花提取物增加了基于细胞的血脑屏障(BBB)模型的紧密性,并增强了Aβ的转运。进一步的体内研究证实了番红花提取物(50 mg/kg/天,添加到小鼠饮食中)对BBB紧密性和功能的影响,其与用作AD模型的5XFAD小鼠中的Aβ负荷降低和相关病理学变化相关。Aβ负荷降低至少部分可通过番红花提取物增强Aβ清除途径(包括BBB清除、酶降解和ApoE清除途径)的作用来解释。此外,番红花提取物上调了突触蛋白,并减少了5XFAD小鼠脑中与Aβ病理学相关的神经炎症。藏红花素是藏红花的主要活性成分,以其抗氧化和抗衰老作用而闻名,也在5XFAD小鼠中单独进行了体内测试。藏红花素(10 mg/kg/天)能够降低Aβ负荷,但与藏红花提取物相比,降低程度较低。总的来说,本研究的结果支持藏红花通过减少Aβ病理表现对AD的积极作用。
Crocus sativus , commonly known as saffron or Kesar, is used in Ayurveda and other folk medicines for various purposes as an aphrodisiac, antispasmodic, and expectorant. Previous evidence suggested that Crocus sativus is linked to improving cognitive function in Alzheimer’s disease (AD) patients. The aim of this study was to in vitro and in vivo investigate the mechanism(s) by which Crocus sativus exerts its positive effect against AD. The effect of Crocus sativus extract on Aβ load and related toxicity was evaluated. In vitro results showed that Crocus sativus extract increases the tightness of a cell-based blood-brain barrier (BBB) model and enhances transport of Aβ. Further in vivo studies confirmed the effect of Crocus sativus extract (50 mg/kg/day, added to mice diet) on the BBB tightness and function that was associated with reduced Aβ load and related pathological changes in 5XFAD mice used as an AD model. Reduced Aβ load could be explained, at least in part, by Crocus sativus extract effect to enhance Aβ clearance pathways including BBB clearance, enzymatic degradation and ApoE clearance pathway. Furthermore, Crocus sativus extract upregulated synaptic proteins and reduced neuroinflammation associated with Aβ pathology in the brains of 5XFAD mice. Crocin, a major active constituent of Crocus sativus and known for its antioxidant and antiinflammatory effect, was also tested separately in vivo in 5XFAD mice. Crocin (10 mg/kg/day) was able to reduce Aβ load but to a lesser extent when compared to Crocus sativus extract. Collectively, findings from this study support the positive effect of Crocus sativus against AD by reducing Aβ pathological manifestations.
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