载Onjisaponin b脂质体的制备与评价通过激活线粒体自噬增强线粒体功能并拯救帕金森病

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Junhua Zhang, Rui Bao, Faisal Raza, Hajra Zafar, Yingjie Qi, Yurui Geng, Ran Li, Jianqin Xue, Feng Shi
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引用次数: 0

摘要

皂苷B (Onjisaponin B, OB)是茯苓的主要活性成分,具有多种生物活性。然而,OB对帕金森病(PD)的保护作用尚未得到充分的研究。脂质体是针对大脑的药物的理想纳米载体。在本研究中,我们研究了负载OB脂质体(lip OB)对1-甲基-4-苯基-1,2,3,6-四氢吡啶- (MPTP-)诱导的PD小鼠模型和1-甲基-4-苯基吡啶- (MPP+-)诱导的PD细胞模型的治疗作用。我们的研究结果表明,唇OB可显著改善mptp诱导的体内运动缺陷和多巴胺能神经元损失,并可防止MPP+引发的体外细胞活力降低和凋亡。Lip OB还通过驱动PINK1/ parkinson介导的线粒体自噬来改善PD模型的线粒体功能障碍。此外,沉默PINK1损害了唇OB对MPP+处理的PC12细胞的有益作用。这些结果提示,唇OB通过线粒体自噬的PINK1/Parkin通路增强线粒体功能障碍,在体内和体外减轻帕金森病,为治疗PD提供了新的可能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Preparation and Evaluation of Onjisaponin B-Loaded Liposomes for Drug Delivery to Enhance Mitochondrial Function and Rescue Parkinson’s Disease by Activating Mitophagy
Onjisaponin B (OB) is the main active ingredient of Radix Polygalae with various bioactivities. However, the protective effect of OB in Parkinson’s disease (PD) has not been fully studied. Liposomes are ideal nanocarriers for drugs targeting the brain. In this study, we investigated the therapeutic effect of OB-loaded liposomes (lip OB) on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced mouse model of PD and 1-methyl-4-phenylpyridinium- (MPP+-) induced cell model of PD. Our results showed that lip OB significantly ameliorated MPTP-induced motor deficits and dopaminergic neuron loss in vivo and prevented MPP+-triggered cell viability reduction and apoptosis in vitro. Lip OB also improved mitochondrial dysfunction in PD models by driving PINK1/Parkin-mediated mitophagy. Furthermore, silencing PINK1 compromised the beneficial effects of lip OB on MPP+-treated PC12 cells. These findings suggested lip OB mitigates Parkinsonism in vivo and in vitro by enhancing mitochondrial dysfunction through the PINK1/Parkin pathway of mitophagy, which provides a new possibility for treating PD.
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来源期刊
CiteScore
4.10
自引率
5.00%
发文量
226
审稿时长
6 months
期刊介绍: The Journal of Clinical Pharmacy and Therapeutics provides a forum for clinicians, pharmacists and pharmacologists to explore and report on issues of common interest. Reports and commentaries on current issues in medical and pharmaceutical practice are encouraged. Papers on evidence-based clinical practice and multidisciplinary collaborative work are particularly welcome. Regular sections in the journal include: editorials, commentaries, reviews (including systematic overviews and meta-analyses), original research and reports, and book reviews. Its scope embraces all aspects of clinical drug development and therapeutics, including: Rational therapeutics Evidence-based practice Safety, cost-effectiveness and clinical efficacy of drugs Drug interactions Clinical impact of drug formulations Pharmacogenetics Personalised, stratified and translational medicine Clinical pharmacokinetics.
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