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靶向关键脂蛋白受体的毛菊苣苷脂质体对小鼠帕金森病模型有效。

Key Lipoprotein Receptor Targeted Echinacoside-Liposomes Effective Against Parkinson's Disease in Mice Model.

机构信息

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People's Republic of China.

出版信息

Int J Nanomedicine. 2024 Aug 19;19:8463-8483. doi: 10.2147/IJN.S468942. eCollection 2024.

DOI:10.2147/IJN.S468942
PMID:39185346
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11342948/
Abstract

INTRODUCTION

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra. The precise molecular mechanisms underlying neuronal loss in PD remain unknown, and there are currently no effective treatments for PD-associated neurodegeneration. Echinacoside (ECH) is known for its neuroprotective effects, which include scavenging cellular reactive oxygen species and promoting mitochondrial fusion. However, the blood-brain barrier (BBB) limits the bioavailability of ECH in the brain, posing a significant challenge to its use in PD treatment.

METHODS

We synthesized and characterized PEGylated ECH liposomes (ECH@Lip) and peptide angiopep-2 (ANG) modified liposomes (ECH@ANG-Lip). The density of ANG in ANG-Lip was optimized using bEnd.3 cells. The brain-targeting ability of the liposomes was assessed in vitro using a transwell BBB model and in vivo using an imaging system and LC-MS. We evaluated the enhanced neuroprotective properties of this formulation in a the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model.

RESULTS

The ECH@ANG-Lip demonstrated significantly higher whole-brain uptake compared to ECH@Lip and free ECH. Furthermore, ECH@ANG-Lip was more effective in mitigating MPTP-induced behavioral impairment, oxidative stress, dopamine depletion, and dopaminergic neuron death than both ECH@Lip and free ECH.

CONCLUSION

The formulation used in our study significantly enhanced the neuroprotective efficacy of ECH in the MPTP-induced PD model. Thus, ECH@ANG-Lip shows considerable potential for improving the bioavailability of ECH and providing neuroprotective effects in the brain.

摘要

简介

帕金森病(PD)是一种常见的神经退行性疾病,其特征是黑质中多巴胺能神经元的退化。PD 中神经元丧失的确切分子机制尚不清楚,目前也没有有效的 PD 相关神经退行性病变治疗方法。松果菊苷(ECH)以其神经保护作用而闻名,包括清除细胞活性氧和促进线粒体融合。然而,血脑屏障(BBB)限制了 ECH 在大脑中的生物利用度,这对其在 PD 治疗中的应用构成了重大挑战。

方法

我们合成并表征了聚乙二醇化 ECH 脂质体(ECH@Lip)和肽血管生成素-2(ANG)修饰的脂质体(ECH@ANG-Lip)。使用 bEnd.3 细胞优化了 ANG-Lip 中的 ANG 密度。通过体外转染 BBB 模型和体内成像系统和 LC-MS 评估了脂质体的脑靶向能力。我们在 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的 PD 模型中评估了这种配方的增强神经保护特性。

结果

ECH@ANG-Lip 与 ECH@Lip 和游离 ECH 相比,表现出明显更高的全脑摄取。此外,ECH@ANG-Lip 比 ECH@Lip 和游离 ECH 更能减轻 MPTP 诱导的行为障碍、氧化应激、多巴胺耗竭和多巴胺能神经元死亡。

结论

我们研究中使用的配方显著增强了 ECH 在 MPTP 诱导的 PD 模型中的神经保护作用。因此,ECH@ANG-Lip 显示出在提高 ECH 的生物利用度和提供脑内神经保护作用方面的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d7b/11342948/9045edd7ff3b/IJN-19-8463-g0012.jpg
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