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印度蜂王浆对冈田酸诱导的大鼠阿尔茨海默病模型的促智作用:抑制神经炎症和乙酰胆碱酯酶。

Nootropic effect of Indian Royal Jelly against okadaic acid induced rat model of Alzheimer's disease: Inhibition of neuroinflammation and acetylcholineesterase.

作者信息

Dubey Rahul, Sathiyanarayanan L, Sankaran Sandeep, Arulmozhi S

机构信息

Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India.

Department of Pharmacy, Government Polytechnic, Ratnagiri, Maharashtra, India.

出版信息

J Tradit Complement Med. 2023 Nov 15;14(3):300-311. doi: 10.1016/j.jtcme.2023.11.005. eCollection 2024 May.

DOI:10.1016/j.jtcme.2023.11.005
PMID:38707922
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11068996/
Abstract

BACKGROUND

Royal jelly is an anti-inflammatory, antioxidant, and neuroprotective bee product. There are several sources for royal jelly and one of them is Indian Royal Jelly (IRJ). However, the neuroprotective actions of IRJ and the underlying molecular mechanisms involved are not well known.

OBJECTIVE

To evaluate the neuroprotective effect of IRJ in the okadaic acid (OKA)-induced Alzheimer's disease (AD) model in rats.

METHODS

In male Wistar rats, OKA was intracerebroventricularly (ICV) administered, and from day 7, they were treated orally with IRJ or memantine for 21 days. Spatial and recognition learning and memory were evaluated from days 27-34; employing the Morris water maze (MWM) and the novel object recognition tests (NORT), respectively. biochemical measurements were taken of the cholinergic system and oxidative stress markers. In silico docking was used to find the role of tau protein kinase and phosphatase in the pharmacological action.

RESULTS

In OKA-induced rats, IRJ decreased the escape latency and path length in MWM and increased the exploration time for novel objects and the discrimination index in NORT. ICV-OKA rats had higher free radicals and cytokines that caused inflammation and their level of free radical scavengers was back to normal with IRJ treatment. IRJ increased the level of acetylcholine and inhibited acetylcholinesterase. Moreover, the in silico docking study revealed the strong binding affinity of 10-hydroxy-2-decenoic acid (10-HDA), a bioactive constituent of IR, to the tau protein kinases and phosphatases.

CONCLUSION

IRJ may serve as a nootropic agent in the treatment of dementia, and owing to its capacity to prevent oxidative stress and neuroinflammation, and increase cholinergic tone; it has the potential to be explored as a novel strategy for the treatment of dementia and AD. More studies may be needed to develop 10-HDA as a novel drug entity for AD.

摘要

背景

蜂王浆是一种具有抗炎、抗氧化和神经保护作用的蜂产品。蜂王浆有多种来源,其中之一是印度蜂王浆(IRJ)。然而,IRJ的神经保护作用及其潜在的分子机制尚不清楚。

目的

评估IRJ对冈田酸(OKA)诱导的大鼠阿尔茨海默病(AD)模型的神经保护作用。

方法

对雄性Wistar大鼠进行脑室注射(ICV)OKA,从第7天开始,给予它们口服IRJ或美金刚,持续21天。在第27至34天评估空间和识别学习及记忆能力,分别采用莫里斯水迷宫(MWM)和新物体识别测试(NORT)。对胆碱能系统和氧化应激标志物进行生化测定。采用计算机对接技术来探究tau蛋白激酶和磷酸酶在药理作用中的作用。

结果

在OKA诱导的大鼠中,IRJ缩短了MWM中的逃避潜伏期和路径长度,并增加了对新物体的探索时间以及NORT中的辨别指数。ICV-OKA大鼠体内自由基和细胞因子水平较高,导致炎症反应,而IRJ治疗后自由基清除剂水平恢复正常。IRJ提高了乙酰胆碱水平并抑制了乙酰胆碱酯酶。此外,计算机对接研究表明,IR的生物活性成分10-羟基-2-癸烯酸(10-HDA)与tau蛋白激酶和磷酸酶具有很强的结合亲和力。

结论

IRJ可能作为一种益智剂用于治疗痴呆,由于其具有预防氧化应激和神经炎症以及增加胆碱能张力的能力,它有潜力被开发为治疗痴呆和AD的新策略。可能需要更多研究来将10-HDA开发为治疗AD的新型药物实体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee5/11068996/c01bae6d4ccb/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee5/11068996/95d71afbf45e/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee5/11068996/32bab63e87b9/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee5/11068996/991bb725deaa/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee5/11068996/3efbc7fea22c/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee5/11068996/820550e8e75d/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee5/11068996/b82e3db92caf/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee5/11068996/4318cfac4ccc/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee5/11068996/c01bae6d4ccb/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee5/11068996/95d71afbf45e/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee5/11068996/32bab63e87b9/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee5/11068996/991bb725deaa/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee5/11068996/3efbc7fea22c/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee5/11068996/820550e8e75d/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee5/11068996/b82e3db92caf/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee5/11068996/4318cfac4ccc/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ee5/11068996/c01bae6d4ccb/gr7.jpg

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