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Anti-epileptic activity of daidzin in PTZ-induced mice model by targeting oxidative stress and BDNF/VEGF signaling.
NeuroToxicology ( IF 3.4 ) Pub Date : 2020-05-23 , DOI: 10.1016/j.neuro.2020.05.005
Zartashia Kazmi 1 , Sara Zeeshan 1 , Adnan Khan 1 , Sumra Malik 2 , Adeeb Shehzad 3 , Eun Kyoung Seo 4 , Salman Khan 1
Affiliation  

Epilepsy is a complex and multifactorial neurodegenerative disease described by recurrent seizures. Oxidative stress and dysregulation of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) are critical factors for the development of epilepsy. Daidzin is well-known for its effective anti-inflammatory and antioxidant potential for centuries. The present study was focused on exploring the anti-epileptic potential of daidzin in the pentylenetetrazole-induced mice model. Daidzin (1, 5, and 10 mg/kg) was administered in the acute study and the dose was optimized. Pretreatment with daidzin remarkably reduced the severity of epileptogenesis in a dose-dependent manner. Moreover, chronic epilepsy was induced in mice by administration of PTZ (35 mg/kg, i.p) every alternative day for 21 days. Results demonstrated that daidzin significantly prevented epileptogenesis and reversed histopathological changes in the hippocampus. It remarkably improved antioxidant (glutathione, glutathione sulfotransferase, superoxide dismutase, and catalase) levels while decreased MDA (malondialdehyde) and nitrite production in the brain. It remarkably improved the expressions of heme oxygenase-1 (HO-1) and BDNF while reduced the expression of VEGF. It remarkably prevented the neuronal apoptosis in the brain tissue. Additionally, spectroscopic analysis such as FTIR (Fourier transform infrared spectroscopy) and DSC (differential scanning calorimetry) revealed that daidzin remarkably prevented PTZ-induced protein damage. HPLC-UV spectrophotometry results demonstrated that there was no peak of aglycone daidzin (metabolite) in the brain sample which specify that the anticonvulsant effect of the compound is due to its direct entry into the brain tissue. Moreover, the molecular docking results showed that daidzin possesses a better binding affinity for ALDH2, estrogen receptor-β, P13k, AKT2, mTORC1, and HIF-1-α proteins. Taken together, the results of the present study showed that daidzin has remarkable neuroprotective and anti-epileptic properties through modulation of oxidative stress, BDNF/VEGF, and apoptotic signaling in the brain tissue of PTZ-kindled mice.



中文翻译:

大豆苷通过靶向氧化应激和BDNF / VEGF信号传导在PTZ诱导的小鼠模型中具有抗癫痫活性。

癫痫病是一种反复发作的复杂多因素神经退行性疾病。氧化应激和脑源性神经营养因子(BDNF)和血管内皮生长因子(VEGF)的失调是癫痫发展的关键因素。大豆黄素具有数百年有效的抗炎和抗氧化潜能。本研究的重点是探索大豆苷在戊四唑诱导的小鼠模型中的抗癫痫潜能。在急性研究中给予大黄素(1、5、10 mg / kg)并优化剂量。大豆苷的预处理以剂量依赖性方式显着降低了癫痫发生的严重性。而且,通过每隔一天施用PTZ(35mg / kg,ip)21天,在小鼠中诱发慢性癫痫。结果表明,大豆苷元可显着预防癫痫发生并逆转海马组织病理学变化。它显着提高了抗氧化剂(谷胱甘肽,谷胱甘肽磺基转移酶,超氧化物歧化酶和过氧化氢酶)的水平,同时降低了大脑中MDA(丙二醛)和亚硝酸盐的产生。它显着改善了血红素加氧酶-1(HO-1)和BDNF的表达,同时降低了VEGF的表达。它显着防止了脑组织中的神经元凋亡。此外,诸如FTIR(傅立叶变换红外光谱法)和DSC(差示扫描量热法)之类的光谱分析表明,大豆苷可以显着防止PTZ诱导的蛋白质损伤。HPLC-UV分光光度法的结果表明,脑样品中没有苷元黄酮(代谢产物)的峰,表明该化合物的抗惊厥作用是由于其直接进入脑组织。此外,分子对接结果表明,大豆苷元对ALDH2,雌激素受体-β,P13k,AKT2,mTORC1和HIF-1-α蛋白具有更好的结合亲和力。综上所述,本研究的结果表明,黄豆苷通过调节PTZ系小鼠的脑组织中的氧化应激,BDNF / VEGF和凋亡信号传导而具有显着的神经保护和抗癫痫特性。雌激素受体-β,P13k,AKT2,mTORC1和HIF-1-α蛋白。综上所述,本研究的结果表明,黄豆苷通过调节PTZ系小鼠的脑组织中的氧化应激,BDNF / VEGF和凋亡信号传导而具有显着的神经保护和抗癫痫特性。雌激素受体-β,P13k,AKT2,mTORC1和HIF-1-α蛋白。综上所述,本研究的结果表明,黄豆苷通过调节PTZ系小鼠的脑组织中的氧化应激,BDNF / VEGF和凋亡信号传导而具有显着的神经保护和抗癫痫特性。

更新日期:2020-05-23
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