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一种改良的中药配方可改善阿尔茨海默病 Tg-APPswe/PS1dE9 小鼠模型的记忆障碍并降低 Aβ 水平。

A modified formulation of Chinese traditional medicine improves memory impairment and reduces Aβ level in the Tg-APPswe/PS1dE9 mouse model of Alzheimer's disease.

机构信息

Dongguk University Research Institute of Biotechnology, 26, 3-GA, Pil-dong, Chung-gu, Seoul 100-715, Republic of Korea.

出版信息

J Ethnopharmacol. 2011 Sep 1;137(1):783-9. doi: 10.1016/j.jep.2011.06.046. Epub 2011 Jul 5.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

SuHeXiang Wan (SHXW), a Chinese traditional medicine has been used orally for the treatment of seizures, infantile convulsion, stroke and so forth. Previously, we reported the effects of modified SHXW essential oil mixture of the fragrance containing herbs on the sedative effect, anticonvulsant property and antioxidative activity after fragrance inhalation.

MATERIALS AND METHODS

This study was undertaken to evaluate beneficial effects of a modified recipe of SHXW (termed as KSOP1009) consisting of a ethanol extract of 8 herbs including resin of Liquidambar orientalis Miller, seed of Myristica fragrans Houtt., rhizome of Cnidium officinale Makino, lumber of Santalum album L., fructus of Piper longum L., flower buds of Eugenia caryophyllata Merrill et Perry, pollen of Typha orientalis Presl., and root of Salvia miltiorrhiza Bunge in the neurodegenerative diseases such as Alzheimer's disease (AD). The transgenic mice of AD, Tg-APPswe/PS1dE9, were fed KSOP1009 or as a positive control, donepezil for 3 months from 4.5 months of age. Behavioral, immunological and ELISA analyses were used to assess memory impairment, Aβ accumulation and plaque deposition in the brain. Other in vitro works were performed to examine whether KSOP1009 inhibits the Aβ(1-42)-induced neurotoxicity in human neuroblastoma cell line, SH-SY5Y cells.

RESULTS

Intake of KSOP1009 improved the Aβ-induced memory impairment and suppressed Aβ levels and plaque deposition in the brain of Tg-APPswe/PS1dE9 mice as much as that of donepezil treatment. KSOP1009 prevented the down-regulation of phospho-CREB and increased AKT phosphorylation in the AD-like brains. Moreover, KSOP1009 suppresses Aβ-induced apoptosis and ROS production in SH-SY5Y cells.

CONCLUSION

The present study suggests that KSOP1009 may develop as a therapeutic drug for treatment of AD patients.

摘要

民族药理学相关性

苏合香丸(SHXW)是一种中药,已被口服用于治疗癫痫、小儿惊厥、中风等。先前,我们报道了含草药的改良 SHXW 精油混合物的香味对镇静作用、抗惊厥作用和吸入香味后的抗氧化活性的影响。

材料和方法

本研究旨在评估由 8 种草药的乙醇提取物组成的改良 SHXW 配方(称为 KSOP1009)对神经退行性疾病(如阿尔茨海默病)的有益作用。AD 转基因小鼠 Tg-APPswe/PS1dE9 从 4.5 个月大开始用 KSOP1009 或作为阳性对照药物多奈哌齐喂养 3 个月。采用行为、免疫和 ELISA 分析来评估记忆障碍、大脑中 Aβ 积累和斑块沉积。进行其他体外工作以检查 KSOP1009 是否抑制 Aβ(1-42)诱导的人神经母细胞瘤细胞系 SH-SY5Y 细胞的神经毒性。

结果

KSOP1009 的摄入改善了 Aβ 引起的记忆障碍,并抑制了 Tg-APPswe/PS1dE9 小鼠大脑中的 Aβ 水平和斑块沉积,与多奈哌齐治疗相当。KSOP1009 防止 AD 样脑中磷酸化 CREB 的下调和 AKT 磷酸化的增加。此外,KSOP1009 抑制 Aβ 诱导的 SH-SY5Y 细胞凋亡和 ROS 产生。

结论

本研究表明,KSOP1009 可能作为治疗 AD 患者的治疗药物开发。

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