Mechanism of neuroprotective effect of stevioside on cerebral ischemia-reperfusion injury via PPAR-γ activation.

IF 3 4区医学 Q3 IMMUNOLOGY

Immunopharmacology and Immunotoxicology Pub Date : 2021-12-01 Epub Date: 2021-08-27 DOI:10.1080/08923973.2021.1966034

Yanli Zhang

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引用次数: 5

Abstract

Objective: The aim of this work was to explore the possible protective effects and its mechanism of stevioside on cerebral ischemia reperfusion (CIR) induced neuron damages.

Methods: Middle cerebral artery occlusion/reperfusion (MCAO/R) rat models were constructed. The rats were treated with stevioside treatment, PPAR-γ antagonist GW9662, PPAR-γ activator pioglitazone or PI3K/AKT inhibitor LY294002 before neurological deficits were assessed using modified Neurological Severity Scale (mNSS) scores. The infarct size, brain injury, apoptotic cells, inflammatory cytokines in neurons extracted from MCAO/R rats were determined by TTC staining, H&E staining, TUNEL staining, qRT-PCR and Western blot, respectively.

Results: Stevioside attenuates MCAO/R-induced neuronal apoptosis and inflammation by regulating PPAR-γ expression. Besides, PPAR-γ activates PI3K/AKT signaling pathway. Moreover, PPAR-γ antagonist GW9662 or PI3K/AKT inhibitor LY294002 abrogated the anti-apoptosis and anti-inflammatory effects of stevioside on MCAO/R rats.

Conclusion: Stevioside alleviates MCAO/R-induced neuronal apoptosis and inflammation by upregulating PPAR-γ to activate PI3K/AKT signaling pathway.

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甜菊苷通过激活PPAR-γ对脑缺血再灌注损伤的神经保护作用机制。

目的:探讨甜菊苷对脑缺血再灌注(CIR)所致神经元损伤的保护作用及其机制。方法:建立大鼠大脑中动脉闭塞/再灌注(MCAO/R)模型。大鼠分别接受甜叶皂苷、PPAR-γ拮抗剂GW9662、PPAR-γ激活剂吡格列酮或PI3K/AKT抑制剂LY294002治疗，然后使用改良神经功能严重程度量表(mNSS)评分评估神经功能缺损。分别采用TTC染色、H&E染色、TUNEL染色、qRT-PCR和Western blot检测MCAO/R大鼠神经元梗死面积、脑损伤、凋亡细胞、炎症因子。结果:甜菊苷通过调节PPAR-γ的表达，减轻MCAO/ r诱导的神经元凋亡和炎症反应。此外，PPAR-γ激活PI3K/AKT信号通路。此外，PPAR-γ拮抗剂GW9662或PI3K/AKT抑制剂LY294002可消除甜菊苷对MCAO/R大鼠的抗凋亡和抗炎作用。结论:甜菊苷通过上调PPAR-γ激活PI3K/AKT信号通路，减轻MCAO/ r诱导的神经元凋亡和炎症。

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

Immunopharmacology and Immunotoxicology 医学-毒理学

CiteScore

5.40

自引率

0.00%

发文量

133

审稿时长

4-8 weeks

期刊介绍： The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal. The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome. With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more. Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).