鞑靼菖蒲（Acorus tatarinowii Schott）的挥发油通过激活 PI3K/AKT 通路改善胰岛素抵抗，从而改善阿尔茨海默氏症。

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2024-10-20 DOI:10.1016/j.phymed.2024.156168

Junhao Huang , Zhiwei Xu , Chenshi Yu , Liu Liu , Liting Ji , Ping Qiu , Changyu Li , Xiaojie Zhou

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引用次数: 0

摘要

背景：阿尔茨海默病（AD）是目前最常见的神经退行性疾病。现有研究强调，胰岛素信号在阿尔茨海默病的发展过程中起着关键作用。在中国，鞑靼菖蒲（SCP）是一种传统的中草药，被用于治疗注意力缺失症。其挥发油（SCP-oil）是其活性成分。目的：本研究采用网络药理学和实验方法，探讨SCP油通过抑制IR改善AD认知能力的作用和机制：采用GC-Q/TOF-MS分析SCP-oil的化学成分，网络药理学预测SCP-oil治疗AD-IR的相关靶点，确定其调控机制。通过脑室内注射链脲佐菌素（ICV-STZ）模拟大脑中的IR。采用莫里斯水迷宫、苏木精和伊红以及Nissl染色法评估SCP-油的神经保护和认知改善作用。采用免疫组织化学和 Western 印迹法分别测定了 Neun 以及与 p-tau、tau、淀粉样蛋白-β（Aβ）、细胞凋亡和磷脂酰肌醇 3- 激酶/蛋白激酶 B（PI3K/AKT）通路相关的蛋白质的表达水平。地塞米松（DXM）诱导的 HT22 细胞用于红外建模。化学分析确定了葡萄糖消耗率，周期性酸性希夫染色检测了糖原沉积。采用 Western 印迹法检测 AD 特征蛋白、凋亡相关蛋白和 PI3K/AKT 通路相关蛋白的表达。流式细胞术检测细胞凋亡率。使用 LY294002 进一步进行反向验证，以评估 PI3K/AKT 通路抑制后 SCP-oil 的药效学效应：结果：SCP 油中共鉴定出 25 种化学成分。网络药理学研究结果表明，SCP-油有可能通过激活 PI3K/AKT 通路来改善大脑中的 IR，从而改善 AD。SCP-oil能明显改善ICV-STZ诱导的认知功能障碍和病理损伤，减少神经元丢失、Aβ沉积和tau蛋白高磷酸化，抑制细胞凋亡，激活PI3K/AKT信号通路。LY294002处理后，神经元丢失、Aβ沉积、tau蛋白高磷酸化和细胞凋亡进一步增强，PI3K/AKT信号通路进一步受到抑制，SCP-oil的保护作用减弱：结论：SCP-油具有改善脑IR的潜力，通过激活PI3K/AKT信号通路抑制细胞凋亡，从而改善学习和记忆能力。

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The volatile oil of Acorus tatarinowii Schott ameliorates Alzheimer's disease through improving insulin resistance via activating the PI3K/AKT pathway

Background

Alzheimer's disease (AD) presently stands as the most prevalent neurodegenerative disease. Existing research underscores the pivotal role of insulin signaling in the progression of AD. Acorus tatarinowii Schott (SCP), a traditional Chinese herbal, is employed for AD treatment in China. The volatile oil of Acorus tatarinowii Schott (SCP-oil) is the active component. However, its impact on AD-associated insulin resistance (AD-IR) remains inadequately investigated.

Purpose

This study used network pharmacology and experimental to investigate the effects and mechanisms of SCP-oil on cognitive improvement in AD by inhibiting IR.

Materials and methods

GC-Q/TOF-MS was employed to analyze the chemical composition of SCP-oil, while network pharmacology predicted the targets associated with SCP-oil in treating AD-IR to identify its regulatory mechanism. IR in the brain was simulated by intracerebroventricular streptozotocin administration (ICV-STZ). The neuroprotective and cognitive improvement effects of SCP-oil were assessed using the Morris water maze and hematoxylin and eosin, as well as Nissl staining. The expression levels of Neun and proteins related to p-tau, tau, amyloid-beta (Aβ), apoptosis, and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway were measured using immunohistochemistry and Western blotting, respectively. Dexamethasone (DXM)-induced HT22 cells were used for IR modeling. Chemical analysis determined the glucose consumption rate, and periodic acid Schiff staining was employed to detect glycogen deposition. Western Blots were utilized to investigate the expression of characteristic AD proteins, apoptosis-related proteins, and PI3K/AKT pathway-related proteins. The apoptosis rate was detected by flow cytometry. Reverse validation was further performed using LY294002 to evaluate the pharmacodynamic effects of SCP-oil after PI3K/AKT pathway inhibition.

Results

A total of 25 chemical constituents were identified in SCP-oil. The network pharmacology findings indicated that SCP-oil holds the potential to ameliorate IR in the brain by activating the PI3K/AKT pathway, thereby improving AD. SCP-oil significantly improved ICV-STZ-induced cognitive dysfunction and pathological damage, reduced neuronal loss, Aβ deposition, and tau protein hyperphosphorylation, inhibited cell apoptosis, and activated the PI3K/AKT signaling pathway. Neuron loss, Aβ deposition, and tau protein hyperphosphorylation and cell apoptosis were further enhanced following treatment with LY294002, while the PI3K/AKT signaling pathway was further inhibited, and the protective effect of SCP-oil was weakened.

Conclusion

SCP-oil exhibited the potential to ameliorate brain IR, inhibiting cell apoptosis by activating the PI3K/AKT signaling pathway, thereby improving learning and memory ability.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.