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首页> 外文期刊>Frontiers in Neuropharmacology >Quercetin Attenuates Diabetic Peripheral Neuropathy by Correcting Mitochondrial Abnormality via Activation of AMPK/PGC-1α Pathway in vivo and in vitro
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Quercetin Attenuates Diabetic Peripheral Neuropathy by Correcting Mitochondrial Abnormality via Activation of AMPK/PGC-1α Pathway in vivo and in vitro

机译：通过在体内和体外激活AMPK / PGC-1α途径校正线粒体异常，槲皮素通过激活校正线粒体异常来衰减糖尿病外周神经病变

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The AMPK/PGC-1α pathway-mediated mitochondrial dysfunction has been supposed to play a crucial role in pathogenesis of diabetic peripheral neuropathy (DPN). The present study investigated the neuroprotective potential of quercetin, a natural AMPK activator. Streptozotocin (STZ)-induced diabetic rats that developed DPN phenotype were orally administrated with quercetin (30 and 60 mg/kg per day) for 6 weeks. The morphologic changes in the sciatic nerves (SN), the pathological structure of neurons in dorsal root ganglion (DRG), and the expressions of myelin proteins were assessed. The ATP content and the mitochondrial ultrastructure were measured. Furthermore, key proteins in the AMPK/PGC-1α pathway were determined. As a result, quercetin administration at both doses improved the paw withdrawal threshold, nerve conduction velocity, and the pathologic changes in SN and DRG of DPN rats. The expressions of myelin basic protein and myelin protein zero were also increased by quercetin. The oxidative stress, decreased ATP generation, and morphological changes of mitochondria were corrected by quercetin. In vitro study found that quercetin treatment significantly decreased the high-glucose-induced generation of reactive oxygen species, as well as attenuated the mitochondrial morphologic injuries and oxidative DNA damages of RSC96 cells. Quercetin treatment promoted the expressions of phosphorylated AMPK, PGC-1α, SIRT1, NRF1, and TFAM under hyperglycemic state in vivo and in vitro. This study revealed that the neuroprotective effect of quercetin was mainly related to mitochondrial protection by activation of the AMPK/PGC-1α pathway for the first time and proved quercetin as a potential therapeutic agent in the management of diabetic neuropathy.
机译：AMPK / PGC-1α途径介导的线粒体功能障碍已经应该在糖尿病外周神经病变（DPN）的发病机制中起着至关重要的作用。本研究研究了天然AMPK活化剂槲皮素的神经保护潜力。链脲佐菌素（STZ）诱导的糖尿病大鼠，其开发DPN表型的槲皮素（每天30和60mg / kg）口服6周。评估坐骨神经（Sn），侧根神经节（DRG）中神经元病理结构的形态学，以及髓鞘蛋白的表达。测量ATP含量和线粒体超微结构。此外，测定AMPK / PGC-1α途径中的键蛋白。结果，两种剂量的槲皮素给药改善了DPN大鼠SN和DRG的爪子取出阈值，神经传导速度和病理变化。槲皮素也增加了髓鞘基础蛋白和髓鞘蛋白零的表达。槲皮素校正了氧化应激，降低的ATP生成和线粒体的形态学变化。体外研究发现，槲皮素治疗显着降低了高葡萄糖诱导的反应性氧物种的产生，以及减弱了RSC96细胞的线粒体形态损伤和氧化DNA损伤。槲皮素治疗在体内和体外促进高血糖状态下磷酸化的AMPK，PGC-1α，SIRT1，NRF1和TFAM的表达。该研究表明，槲皮素的神经保护作用主要与第一次激活AMPK / PGC-1α途径的线粒体保护，并证明了糖尿病神经病变管理中的潜在治疗剂的槲皮素。

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