Kim Sang-Ho, Chung Dae-Kyoo, Lee Young Joon, Song Chang-Hyun, Ku Sae-Kwang
Department of Oriental Neuropsychiatry, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea.
Department of Preventive Medicine, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea.
J Ethnopharmacol. 2016 Jul 21;188:123-33. doi: 10.1016/j.jep.2016.04.060. Epub 2016 May 6.
Dangui-Jakyak-San (DJ) is a traditional Korean medicinal polyherb, prescribed typically in patients with insufficient blood supply in Eastern Asia. The DJ also has been reported to have neuroprotective effects in vitro and in vivo studies.
The therapeutic potential of DJ was examined in stroke rat model, in comparison with donepezil, a reversible acetylcholinesterase inhibitor.
Ischemic stroke rat model was induced by surgery of permanent occlusion of middle cerebral artery (pMCAO). The model was orally administered with distilled water (pMCAO control), donepezil at 10mg/kg (Donepezil) and DJ at 200, 100 and 50mg/kg (DJ 200, DJ 100 and DJ 50, respectively). Sham had the same surgery excepting for the pMCAO, and it was administered with distilled water (sham control).
After the administration for 28 days, the groups of DJ exhibited dose-dependent reduction in infarct/defect volumes with improvement in sensorimotor and cognitive motor function, comparing to pMCAO control. The DJ treatments seemed to enhance antiapoptotic and antioxidant effects; increases in antiapoptotic expressions (STAT3 and Pim-1) and decreases in lipid peroxidation (MDA) together with increases in contents of endogenous antioxidant (GSH) and activities of antioxidant enzymes (catalase and SOD). The histopathological analyses revealed significant reduction in neuronal apoptosis (caspase-3 and PARP) and neuronal degradation with atrophy and degeneration, in the DJ treatments. Furthermore, the oxidative stresses (nitrotyrosine as an iNOS factor and 4-HNE as a marker of lipid peroxidation) were observed mild. Although the similar neuroprotective effects were observed, the body weight loss was scarcely alleviated in Donepezil comparing to pMCAO control.
These suggest that DJ ameliorate the neurological dysfunction of cerebral ischemia through augmentation of antioxidant defense system and up-regulation of STAT3 and Pim-1.
当归加芍药散（DJ）是一种传统的韩国复方草药，在东亚地区常用于血液供应不足的患者。体外和体内研究也报道了DJ具有神经保护作用。
与可逆性乙酰胆碱酯酶抑制剂多奈哌齐相比，在中风大鼠模型中研究DJ的治疗潜力。
通过大脑中动脉永久性闭塞手术（pMCAO）诱导缺血性中风大鼠模型。模型分别口服蒸馏水（pMCAO对照组）、10mg/kg多奈哌齐（多奈哌齐组）和200、100和50mg/kg的DJ（分别为DJ 200、DJ 100和DJ 50组）。假手术组除不进行pMCAO外，其余手术相同，且口服蒸馏水（假手术对照组）。
给药28天后，与pMCAO对照组相比，DJ各剂量组梗死/缺损体积呈剂量依赖性减小，感觉运动和认知运动功能得到改善。DJ治疗似乎增强了抗凋亡和抗氧化作用；抗凋亡表达（STAT3和Pim-1）增加，脂质过氧化（MDA）减少，同时内源性抗氧化剂（GSH）含量增加，抗氧化酶（过氧化氢酶和超氧化物歧化酶）活性增强。组织病理学分析显示，DJ治疗组神经元凋亡（caspase-3和PARP）以及神经元萎缩和变性导致的神经元降解显著减少。此外，氧化应激（作为诱导型一氧化氮合酶因子的硝基酪氨酸和作为脂质过氧化标志物的4-羟基壬烯醛）较轻。虽然观察到了类似的神经保护作用，但与pMCAO对照组相比，多奈哌齐组体重减轻几乎未得到缓解。
这些结果表明，DJ通过增强抗氧化防御系统以及上调STAT3和Pim-1来改善脑缺血的神经功能障碍。
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