负载白藜芦醇的谷胱甘肽涂层胶原纳米颗粒通过抑制小鼠海马体中的 HMGB1 和 TLR-4 来减轻急性癫痫发作,ACS Chemical Neuroscience

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负载白藜芦醇的谷胱甘肽涂层胶原纳米颗粒通过抑制小鼠海马体中的 HMGB1 和 TLR-4 来减轻急性癫痫发作
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2022-04-06 , DOI: 10.1021/acschemneuro.2c00171
Mobin A Siddiqui ₁ , Mohammad Asad ₂ , Juheb Akhter ₃ , Ubedul Hoda ₄ , Shweta Rastogi ₅ , Indu Arora ₆ , Nidhi B Aggarwal ₄ , Mohammed Samim ₁

Affiliation

癫痫是一种相对复杂的神经系统疾病，会导致癫痫发作。最近的研究报告了使用白藜芦醇治疗癫痫发作。然而，白藜芦醇的低生物利用度和难以到达大脑中的目标位置会大大降低其功效。由于药物浓度较高而引起的副作用是另一个值得关注的问题。本研究的目的是通过将白藜芦醇包裹在谷胱甘肽涂层的胶原纳米粒子中，将其递送至大脑的目标位置，从而增强其抗癫痫潜力。胶原蛋白纳米颗粒增加了白藜芦醇的生物利用度，而谷胱甘肽促进了白藜芦醇向大脑中目标位置的转运。通过将白藜芦醇包裹在谷胱甘肽涂层的胶原纳米颗粒中，浓度也大大降低。包裹在合成纳米颗粒中的白藜芦醇称为纳米白藜芦醇。在本研究中，通过 PTZ 诱发的癫痫发作 (PTZ-IS) 和增加电流电击 (ICES) 测试研究了纳米白藜芦醇的有效性。通过生化分析、组织病理学检查、ELISA 和实时 PCR 测试以及小鼠海马的免疫组织化学检查，进一步确定了纳米白藜芦醇的功效。因此，这项研究的独特之处在于它通过使用谷胱甘肽涂层的胶原纳米粒子合成了纳米白藜芦醇，然后将其应用于治疗癫痫发作。根据研究结果，纳米白藜芦醇被发现在预防小鼠认知障碍和控制癫痫发作方面比白藜芦醇更有效。所提出的纳米制剂还显着降低了白藜芦醇的浓度。目前的研究结果表明，即使是 0.4 mg/kg 的纳米白藜芦醇也优于 40 mg/kg 的白藜芦醇。

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Resveratrol-Loaded Glutathione-Coated Collagen Nanoparticles Attenuate Acute Seizures by Inhibiting HMGB1 and TLR-4 in the Hippocampus of Mice

Epilepsy is a relatively complicated neurological disorder that results in seizures. The use of resveratrol in treating seizures has been reported in recent studies. However, the low bioavailability of resveratrol and the difficulty of reaching the targeted location in the brain reduce its efficacy considerably. The side effects due to the higher concentration of drugs are another matter of concern. The purpose of the present study is to enhance the antiepileptic potential of resveratrol by delivering it to the brain’s targeted location by encapsulating it in glutathione-coated collagen nanoparticles. The collagen nanoparticles increase the bioavailability of resveratrol, while the transport of resveratrol to its target location in the brain is facilitated by glutathione. By encapsulating resveratrol in glutathione-coated collagen nanoparticles, the concentration also substantially decreases. Resveratrol encapsulated in synthesized nanoparticles is referred to as nanoresveratrol. In the present study, nanoresveratrol effectiveness was studied through PTZ-induced seizures (PTZ-IS) and the increasing current electroshock (ICES) test. The efficacy of nanoresveratrol was further established using biochemical analysis, histopathological examinations, ELISA and real-time-PCR tests, and immunohistochemistry examination of the hippocampus of mice. Hence, this study is unique in the sense that it synthesized nanoresveratrol by using glutathione-coated collagen nanoparticles, followed by its application to treating seizures. On the basis of the study results, nanoresveratrol was found to be effective in preventing cognitive impairment in the mice and controlling epilepsy seizures to a greater extent than resveratrol. The proposed nanoformulation also reduces the concentration of resveratrol considerably. The present study results show that even 0.4 mg/kg of nanoresveratrol outperforms 40 mg/kg of resveratrol.

更新日期：2022-04-06

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