Neuroprotective Effect of Ganoderic Acid against Focal Ischemic Stroke Induced by Middle Cerebral Artery Occlusion in the Rats via Suppression of Oxidative Stress and Inflammation

IF 0.8 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Doklady Biochemistry and Biophysics Pub Date : 2024-07-18 DOI:10.1134/S1607672924600313

Yong Liu, Xuemei Feng, Juan Wang, Mingfen Li

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引用次数: 0

Abstract

Stroke is recognized as a leading cause of disability and mortality worldwide, posing a significant challenge, particularly in developing countries. The current study aimed to evaluate the neuroprotective effect of Ganoderic acid (GA) against focal ischemic stroke in rats.

Swiss Wistar rats were used for the current study. The rats were subjected to middle cerebral artery occlusion (MCAO) to simulate transient focal ischemia, followed by reperfusion. Various neurological parameters, including infarct size, neurological deficit score, brain water content, Evans blue leakage, nitric oxide (NO), inducible nitric oxide synthase (iNOS), lactate dehydrogenase (LDH), antioxidant levels, inflammatory cytokines, apoptosis markers, inflammatory parameters, and matrix metalloproteinases (MMP) levels, were estimated. Additionally, mRNA expressions were evaluated in the brain tissue.

Dose dependently treatment of GA significantly (P < 0.001) suppressed the infarct size, neurological deflects score, brain water, evans blue leakage, NO, iNOS, LDH, C-X-C chemokine receptor type 4 (CXCR-4), monocyte chemoattractant protein-1 (MCP-1), S100 calcium-binding protein B (S-100β) and K+-Cl− cotransporter 1 (KCC1) positive cells. GA altered the level of oxidative stress parameters like Total antioxidant capacity (T-AOC), 8-hydroxy-2'-deoxyguanosine (8-OhdG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), malonaldehyde (MDA); cytokines viz., tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-1β, IL-6, IL-9, IL-10; inflammatory parameters such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin (PGE₂), Nuclear factor kappa B (NF-κB); apoptosis parameters like B-cell leukemia/lymphoma 2 protein (Bcl-2), Bcl-2-associated protein x (Bax), Caspase-3; matrix metallopeptidase (MMP) parameters like MMP-2, MMP-3, and MMP-9, respectively. GA remarkably suppressed the mRNA expression of TRL-4, Syndecan-1, CSF, Aquaporin-1, OCT3, and RFX1.

Ganoderic acid exhibited the protection against the cerebral ischemia reperfusion via multiple mechanism.

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十二酸通过抑制氧化应激和炎症对大脑中动脉闭塞引起的大鼠局灶性缺血性脑卒中的神经保护作用

中风被认为是全世界致残和致死的主要原因，尤其是在发展中国家，这构成了一项重大挑战。本研究旨在评估芝麻酸（GA）对大鼠局灶性缺血性中风的神经保护作用：本研究使用瑞士 Wistar 大鼠。对大鼠进行大脑中动脉闭塞（MCAO）以模拟短暂的局灶性缺血，然后进行再灌注。研究人员估算了各种神经参数，包括脑梗塞大小、神经功能缺损评分、脑含水量、埃文斯蓝渗漏、一氧化氮（NO）、诱导型一氧化氮合酶（iNOS）、乳酸脱氢酶（LDH）、抗氧化剂水平、炎症细胞因子、细胞凋亡标志物、炎症参数和基质金属蛋白酶（MMP）水平。此外，还评估了脑组织中的 mRNA 表达：结果：GA的剂量依赖性治疗能明显（P<0.001）抑制脑梗塞大小、神经功能偏移评分、脑水、evans蓝渗漏、NO、iNOS、LDH、C-X-C趋化因子受体4型（CXCR-4）、单核细胞趋化蛋白-1（MCP-1）、S100钙结合蛋白B（S-100β）和K+-Cl-共转运体1（KCC1）阳性细胞。GA 改变了氧化应激参数的水平，如总抗氧化能力（T-AOC）、8-羟基-2'-脱氧鸟苷（8-OhdG）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）、谷胱甘肽（GSH）、丙二醛（MDA）；细胞因子，即：肿瘤坏死因子-α（α-GA）、肿瘤坏死因子-α（α-GA）、肿瘤坏死因子-α（α-GA）和肿瘤坏死因子-α（α-GA）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1（IL-1）、IL-1β、IL-6、IL-9、IL-10；炎症指标，如诱导型一氧化氮合酶（iNOS）、环氧化酶-2（COX-2）、前列腺素（PGE2）、核因子卡巴 B（NF-κB）；凋亡参数，如 B 细胞白血病/淋巴瘤 2 蛋白（Bcl-2）、Bcl-2 相关蛋白 x（Bax）、Caspase-3；基质金属肽酶（MMP）参数，如 MMP-2、MMP-3 和 MMP-9。GA 显著抑制了 TRL-4、Syndecan-1、CSF、Aquaporin-1、OCT3 和 RFX1 的 mRNA 表达：结论：灵芝酸通过多种机制对脑缺血再灌注具有保护作用。

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来源期刊

Doklady Biochemistry and Biophysics 生物-生化与分子生物学

CiteScore

1.60

自引率

12.50%

发文量

审稿时长

6-12 weeks

期刊介绍： Doklady Biochemistry and Biophysics is a journal consisting of English translations of articles published in Russian in biochemistry and biophysics sections of the Russian-language journal Doklady Akademii Nauk. The journal''s goal is to publish the most significant new research in biochemistry and biophysics carried out in Russia today or in collaboration with Russian authors. The journal accepts only articles in the Russian language that are submitted or recommended by acting Russian or foreign members of the Russian Academy of Sciences. The journal does not accept direct submissions in English.