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载道诺林的鼻腔给药:用于阿尔茨海默病的多靶点治疗。

Intranasal administration of dauricine loaded on graphene oxide: multi-target therapy for Alzheimer's disease.

机构信息

School of Pharmacy, Guilin Medical University, Guilin, China.

School of Pharmacy, Zhejiang Chinese Medical University, Zhejiang, China.

出版信息

Drug Deliv. 2021 Dec;28(1):580-593. doi: 10.1080/10717544.2021.1895909.

Abstract

Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by progressive cognitive and memory-related impairment. However, current therapeutic treatments have not proved sufficiently effective, mainly due to the complicated pathogenesis of the disease. In this study, a nano-formulation of graphene oxide (GO) loaded with dauricine (Dau) was investigated in terms of the combined anti-inflammatory and anti-oxidative stress effects of Dau and the inhibition of misfolding and aggregation of the amyloid-β (Aβ) protein by GO. Both and models were induced using Aβ, and the formulation was administered nasally in mice. The results showed that GO loaded with Dau greatly reduced oxidative stress through increasing superoxide dismutase levels and decreasing reactive oxygen species and malondialdehyde levels ; it also alleviated the cognitive memory deficits and brain glial cell activation in mice with Aβ-induced AD. This proved that GO loaded with Dau could protect against Aβ-induced oxidative damage and apoptosis in both and AD models; therefore, GO loaded with Dau has the potential to be an effective and agent for the rapid treatment of AD.

摘要

阿尔茨海默病(AD)是一种中枢神经系统退行性疾病,其特征是进行性认知和记忆障碍。然而,目前的治疗方法效果并不理想,主要是由于该疾病的发病机制复杂。在这项研究中,研究人员考察了载有冬凌草甲素(Dau)的氧化石墨烯(GO)纳米制剂在 Dau 的抗炎和抗氧化应激作用以及 GO 抑制淀粉样蛋白-β(Aβ)蛋白错误折叠和聚集方面的联合作用。使用 Aβ 诱导了 和 模型,然后通过鼻腔向小鼠给药。结果表明,载有 Dau 的 GO 通过增加超氧化物歧化酶水平和降低活性氧和丙二醛水平,极大地减轻了氧化应激;它还缓解了 Aβ 诱导的 AD 小鼠的认知记忆缺陷和脑神经胶质细胞激活。这证明了载有 Dau 的 GO 可以防止 Aβ 诱导的 和 两种 AD 模型中的氧化损伤和细胞凋亡;因此,载有 Dau 的 GO 有可能成为治疗 AD 的有效和快速治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fb4/7971267/4c6e36f12ca7/IDRD_A_1895909_F0001_C.jpg

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