Abstract

Context

Recently in Korean medicine, the antioxidant and anti-inflammatory activities of Seonghyangjeongki-san (SHJKS) were reported. However, studies on the specific mechanisms of action of SHJKS for the treatment of ischaemic stroke are still lacking.

Objective

This study investigates the mechanism of action of the water extract methanol fraction of modified SHJKS (SHJKSmex) on cerebral ischaemic injury.

Materials and methods

C57BL/6 male mice were orally administered SHJKSmex (30, 100, or 300 mg/kg) for 3 consecutive days (2 days, 1 day, and 1 h, respectively) before middle cerebral artery occlusion (MCAO). Twenty-four hours after MCAO, the infarct volumes were measured, brain edoema indices were calculated, and neurological deficit scores were determined. Inflammation-related substances in the ipsilateral hemisphere were determined by western blotting, dichlorofluorescin diacetate, thiobarbituric acid-reactive substances assay, and enzyme-linked immunosorbent assay.

Results

SHJKSmex pre-treatment at 300 mg/kg decreased infarct volume by 87% and mean brain water content by 90% of the MCAO control group. Moreover, SHJKSmex effectively suppressed the expression of inducible nitric oxide synthase, reactive oxygen species, interleukin 1, and caspases-8 and −9 and increased the B-cell lymphoma 2/Bcl-2-associated X protein ratio (Bcl-2/Bax) in ischaemic mouse brain. The hippocampal pyramidal cell densities were significantly increased in the 300 mg/kg SHJKSmex-administered group compared to the MCAO control group.

Discussion and conclusions

SHJKSmex protected the brain from ischaemic stroke in mice through its antioxidant, anti-inflammatory, and antiapoptotic activities. Our findings suggest that SHJKSmex is a promising therapeutic candidate for the development of a new formulation for ischaemia-induced brain damage.

中文翻译：

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改良成香正基山水提物甲醇馏分对小鼠短暂性缺血性脑损伤的影响

摘要

语境

最近在韩国医学中，报道了 Seonghyangjeongki-san (SHJKS) 的抗氧化和抗炎活性。然而，尚缺乏关于SHJKS治疗缺血性脑卒中的具体作用机制的研究。

客观的

本研究探讨改性SHJKS（SHJKSmex）水提甲醇馏分对脑缺血性损伤的作用机制。

材料和方法

C57BL/6 雄性小鼠在大脑中动脉闭塞 (MCAO) 前连续 3 天（分别为 2 天、1 天和 1 小时）口服 SHJKSmex（30、100 或 300 mg/kg）。MCAO 后 24 小时，测量梗死体积，计算脑水肿指数，并确定神经功能缺损评分。同侧半球炎症相关物质通过蛋白质印迹、二氯荧光素二乙酸盐、硫代巴比妥酸反应物质测定和酶联免疫吸附测定测定。

结果

300 mg/kg 的 SHJKSmex 预处理使 MCAO 对照组的梗塞体积减少了 87%，平均脑含水量减少了 90%。此外，SHJKSmex 有效抑制诱导型一氧化氮合酶、活性氧、白细胞介素 1、caspase-8 和 -9 的表达，并增加 B 细胞淋巴瘤 2/Bcl-2 相关 X 蛋白比率（Bcl-2/Bax ) 在缺血性小鼠脑中。与 MCAO 对照组相比，300 mg/kg SHJKSmex 给药组的海马锥体细胞密度显着增加。

讨论和结论

SHJKSmex 通过其抗氧化、抗炎和抗凋亡活性保护大脑免受缺血性中风的影响。我们的研究结果表明，SHJKSmex 是一种很有前途的治疗候选药物，可用于开发用于治疗缺血性脑损伤的新制剂。