College of Korean Medicine, Dong-Eui University, Busan, Republic of Korea.
School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea.
Pharm Biol. 2021 Dec;59(1):840-853. doi: 10.1080/13880209.2021.1941130.
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.
This study investigates the mechanism of action of the water extract methanol fraction of modified SHJKS (SHJKSmex) on cerebral ischaemic injury.
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.
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.
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.
最近在韩医学中，报道了生黄精煎剂（SHJKS）的抗氧化和抗炎活性。然而，对于 SHJKS 治疗缺血性中风的具体作用机制的研究仍然缺乏。
本研究旨在探讨改良生黄精煎剂（SHJKSmex）水提甲醇部位对脑缺血损伤的作用机制。
C57BL/6 雄性小鼠连续 3 天（分别为 2 天、1 天和 1 小时前）口服给予 SHJKSmex（30、100 或 300mg/kg），然后进行大脑中动脉闭塞（MCAO）。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。通过 Western blot、二氯荧光素二乙酸酯、硫代巴比妥酸反应性物质测定和酶联免疫吸附试验测定对侧半球的炎症相关物质。
300mg/kg 的 SHJKSmex 预处理可使 MCAO 对照组的梗死体积减少 87%，大脑含水量减少 90%。此外，SHJKSmex 有效抑制了诱导型一氧化氮合酶、活性氧、白细胞介素 1 和半胱天冬酶-8 和 -9 的表达，并增加了缺血性小鼠脑中 B 细胞淋巴瘤 2/Bcl-2 相关 X 蛋白的比值（Bcl-2/Bax）。与 MCAO 对照组相比，300mg/kg 的 SHJKSmex 给药组海马锥体神经元密度显著增加。
SHJKSmex 通过其抗氧化、抗炎和抗凋亡作用保护了小鼠的大脑免受缺血性中风的影响。我们的研究结果表明，SHJKSmex 是一种有前途的治疗候选药物，可用于开发治疗缺血性脑损伤的新制剂。
