The potential therapeutic role of Lisinopril in augmenting the striatal neuroplasticity via the striatal ACE2/Ang1-7/MAS receptor axis in 3-nitropropionic acid-induced Huntington’s disease in rats: shifting paradigms in Huntington’s disease treatment

IF 3.4 Q2 PHARMACOLOGY & PHARMACY

Future Journal of Pharmaceutical Sciences Pub Date : 2024-11-04 DOI:10.1186/s43094-024-00724-z

Hanaa Wanas, Mostafa Adel Rabie, Basma Emad Aboulhoda, Nagwa Mahmoud Ramadan, Sahar Abdelwahab, Sara Sayed Kadry Abdallah, Eid Nassar Ali, Leyan Nasruddeen Khayruddeen, Yasir Hassan Elhassan, Hadel Mahroos Alghabban, Shaimaa Mohamed Abdelsalam, Amira Karam Khalifa

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引用次数: 0

Abstract

Background

The exact pathogenesis of Huntington’s disease (HD) remains unclear. However, mitochondrial dysfunction and oxidative stress are supposed to play a significant role. The objective of this study was to examine the possible neuroprotective effect of Lisinopril (Lisino) in a 3-nitropropionic acid-produced HD in rats.

Methods

Sixty-four rats were divided into four groups (16/group): Group (1): Normal control group, Group (2): Lisinopril control group, Group (3): 3-NP non-treated group, and Group (4): (3-NP + Lisinopril) group. Behavior assessments (open field test, rotarod test, grip strength test) were performed along with different histological and biochemical parameters.

Results

Lisinopril upregulated the expression of the ACE2/Ang1-7/MAS receptor (MasR) axis of RAS, which triggered the PI3K/Akt pathway and prompted the CREB/BDNF neurogenesis signal. Furthermore, Lisinopril remarkably downregulated the inflammatory cytokines (NF-κB, TNF-α, IFN-γ and IL-6), decreased apoptotic markers (p53, BAX/Bcl2 ratio, Cyt-c and caspase-3) and upgraded the mitochondrial TFAM content and SDH activity along with restoration of the redox mechanism by recovering SOD, catalase, GSH and Nrf2.

Conclusion

Notably, the outcomes of this study disclosed that Lisinopril could be a future neuroprotective therapeutic candidate against HD.

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利辛普利通过纹状体 ACE2/Ang1-7/MAS 受体轴增强纹状体神经可塑性对 3-硝基丙酸诱导的亨廷顿氏病大鼠的潜在治疗作用：亨廷顿氏病治疗范式的转变

背景亨廷顿氏病（HD）的确切发病机制仍不清楚。然而，线粒体功能障碍和氧化应激被认为在其中发挥了重要作用。本研究旨在探讨利辛普利（Lisino）对 3-硝基丙酸所致亨廷顿氏病大鼠神经保护作用的可能性。方法将 64 只大鼠分为四组（16 只/组）：组（1）：正常对照组；(2)利辛普利对照组；(3)3-NP未处理组和（4）组：(3-NP+利辛普利）组。结果利辛普利上调了RAS的ACE2/Ang1-7/MAS受体（MasR）轴的表达，从而触发了PI3K/Akt通路，并促进了CREB/BDNF神经发生信号。此外，利辛普利还显著降低了炎症细胞因子（NF-κB、TNF-α、IFN-γ和IL-6），减少了凋亡标志物（p53、BAX/Bcl2比值、Cyt-c和caspase-3），提高了线粒体TFAM含量和SDH活性，并通过恢复SOD、过氧化氢酶、GSH和Nrf2恢复了氧化还原机制。结论值得注意的是，本研究结果表明，利辛普利可能是未来治疗 HD 的神经保护候选药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Future Journal of Pharmaceutical Sciences PHARMACOLOGY & PHARMACY-

自引率

0.00%

发文量

审稿时长

23 weeks

期刊介绍： Future Journal of Pharmaceutical Sciences (FJPS) is the official journal of the Future University in Egypt. It is a peer-reviewed, open access journal which publishes original research articles, review articles and case studies on all aspects of pharmaceutical sciences and technologies, pharmacy practice and related clinical aspects, and pharmacy education. The journal publishes articles covering developments in drug absorption and metabolism, pharmacokinetics and dynamics, drug delivery systems, drug targeting and nano-technology. It also covers development of new systems, methods and techniques in pharmacy education and practice. The scope of the journal also extends to cover advancements in toxicology, cell and molecular biology, biomedical research, clinical and pharmaceutical microbiology, pharmaceutical biotechnology, medicinal chemistry, phytochemistry and nutraceuticals.