Neuroprotective effect of Chunghyuldan from amyloid beta oligomer induced neuroinflammation in vitro and in vivo

作者：Kim Hyo Geun; Kim Ji Young; Whang Wei Wan; Oh Myung Sook^*

来源：Canadian Journal of Physiology and Pharmacology, 2014, 92(6): 429-437.

DOI：10.1139/cjpp-2013-0229

• Chunghyuldan
• oligomeric form of amyloid-beta
• Alzheimer%26apos
• s disease
• neuroinflammation

Microglia-mediated inflammation is a major pathological mechanism contributing to Alzheimer%26apos;s disease (AD), and has been proposed as a potential therapeutic target. Chunghyuldan (CHD; Qingxue-dan in Chinese and Daio-Orengedokuto in Japanese) possesses wide-ranging biological effects, including anti-hyperlipidemic, anti-stroke, anti-inflammatory, and antioxidant activities that could affect neurological functions. In this study, we examined the effects of CHD in in-vitro and in-vivo models of AD induced by the oligomeric form of amyloid-beta (A beta oligomer), which acts directly on microglia-mediated neuroinflammation to result in neuronal damage and cognitive impairment. CHD at 0.1-100 mu g.mL(-1) significantly protected PC12 cells and rat primary hippocampal cells from A beta oligomer(1-42) toxicity. In addition, CHD at 1-10 mu g.mL(-1) inhibited A beta oligomer(1-42) induced production of nitric oxide, tumor necrosis factor-alpha, and interleukin-1 beta in microglial cells. In an in-vivo AD model, administration of CHD (50 mg.(kg body mass)(-1), for 5 days, per oral) inhibited the activation of astrocytes and microglia in the dentate gyrus and neuronal damage in the CA1 of the ipsilateral hippocampus. Moreover, CHD ameliorated cognitive impairment induced by A beta oligomer(1-42) toxicity. These results demonstrate the neuroprotective effects of CHD through inhibition of microglia-mediated neuroinflammation in in-vitro and in-vivo AD-like models induced by A beta oligomer(1-42) toxicity.

• 出版日期2014-6