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Luteolin Protects Against CIRI, Potentially via Regulation of the SIRT3/AMPK/mTOR Signaling Pathway.
Neurochemical Research ( IF 3.7 ) Pub Date : 2020-08-18 , DOI: 10.1007/s11064-020-03108-w
Shuwen Liu 1, 2 , Yu Su 1 , Bixi Sun 1 , Rubin Hao 1, 2 , Siqi Pan 1 , Xiaoshu Gao 1 , Xinyue Dong 1 , Ahmed Mohammed Ismail 1 , Bing Han 1
Affiliation  

Mitochondrial abnormalities accelerate the progression of ischemic brain damage. Sirtuin 3 (SIRT3) is mainly found in mitochondria and affects almost all major aspects of mitochondrial function. Luteolin, a flavonoid with diverse biological properties, including antioxidant activity, inhibition of cell apoptosis and regulation of autophagy. It also modulates the activity of AMP activated kinase and/or sirtuin 1 (SIRT 1) by regulating the expression of sirtuins. We investigated the protective effects of luteolin on cerebral ischemia-reperfusion. It was found through experiments that luteolin reduced the infarcted area of MCAO rat model, and based on the experimental results, it was inferred that luteolin affected the AMPK, mTOR and SIRT3 pathways, thereby protecting brain cells. As expected, we found that luteolin can reduce the neurological function score, the degree of cerebral edema, the cerebral infarction volume, alleviate morphological changes in the cortex and hippocampus, increase neuron survival and decrease the number of apoptotic neurons. At the same time, luteolin significantly reduced the number of GFAP and Iba-1 positive glial cells in the hippocampus while enhanced the scavenging of oxygen free radicals and the activity of SOD in mitochondria. Addtionally, it can also enhance antioxidant capacity via the reversal of mitochondrial swelling and the mitochondrial transmembrane potential. Moreover, luteolin can increase SIRT3-targeted expression in mitochondria, decrease the phosphorylation of AMPK, and increase phosphor-mTOR (p-mTOR) levels, which may have occurred specifically through activation of the SIRT3/AMPK/mTOR pathway. We speculate that luteolin reduces the pathological progression of CIRI by increasing SIRT3 expression and enhancing mitochondrial function. Therefore, the results indicate that luteolin can increase the transduction of SIRT3, providing a potential mechanism for neuroprotective effects in patients with cerebral ischemia.



中文翻译:

木犀草素可能通过SIRT3 / AMPK / mTOR信号通路的调控来预防CIRI。

线粒体异常加速缺血性脑损伤的进展。Sirtuin 3(SIRT3)主要存在于线粒体中,几乎影响线粒体功能的所有主要方面。木犀草素,一种具有多种生物学特性的类黄酮,包括抗氧化活性,抑制细胞凋亡和调节自噬。它还通过调节沉默调节蛋白的表达来调节AMP激活的激酶和/或沉默调节蛋白1(SIRT 1)的活性。我们调查了木犀草素对脑缺血再灌注的保护作用。通过实验发现木犀草素减少了MCAO大鼠模型的梗塞面积,并且基于实验结果,推断木犀草素影响了AMPK,mTOR和SIRT3途径,从而保护了脑细胞。不出所料 我们发现木犀草素可以降低神经功能评分,减轻脑水肿程度,减少脑梗死体积,减轻皮质和海马的形态变化,增加神经元存活率并减少凋亡神经元的数量。同时,木犀草素显着减少了海马中的GFAP和Iba-1阳性胶质细胞的数量,同时增强了线粒体中氧自由基的清除和SOD的活性。另外,它还可以通过逆转线粒体肿胀和线粒体跨膜电位来增强抗氧化能力。此外,木犀草素可以增加线粒体中针对SIRT3的表达,降低AMPK的磷酸化,并增加磷-mTOR(p-mTOR)水平,这可能是由于SIRT3 / AMPK / mTOR途径的激活而发生的。我们推测木犀草素通过增加SIRT3表达和增强线粒体功能来降低CIRI的病理进展。因此,结果表明木犀草素可以增加SIRT3的转导,为脑缺血患者的神经保护作用提供了潜在的机制。

更新日期:2020-09-23
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