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Neuroprotective effect of Chunghyuldan from amyloid beta oligomer induced neuroinflammation in vitro and in vivo Hyo Geun Kim, Ji-Young Kim, Wei-Wan Whang, and Myung Sook Oh

Abstract: Microglia-mediated inflammation is a major pathological mechanism contributing to Alzheimer'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␤ oligomer), which acts directly on microglia-mediated neuroinflammation to result in neuronal damage and cognitive impairment. CHD at 0.1–100 ␮g·mL−1 significantly protected PC12 cells and rat primary hippocampal cells from A␤ oligomer1–42 toxicity. In addition, CHD at 1–10 ␮g·mL−1 inhibited A␤ oligomer1–42 induced production of nitric oxide, tumor necrosis factor-␣, and interleukin-1␤ 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␤ oligomer1–42 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␤ oligomer1–42 toxicity. Key words: Chunghyuldan, oligomeric form of amyloid-beta, Alzheimer’s disease, neuroinflammation. Résumé : L'inflammation dépendante de la microglie constitue un mécanisme pathologique important qui contribue a` la maladie d'Alzheimer (MA), et elle a été proposée comme cible thérapeutique potentielle. Le Chunghyuldan (CHD, Qingxue-dan en Chinois et Daio-Orengedokuto en Japonais) possède un large spectre d'effets biologiques, y compris des activités antihyperlipémiques, anti-AVC, anti-inflammatoires et anti-oxydantes qui pourraient affecter les fonctions neurologiques. Dans cette étude, les auteurs ont examiné les effets du CHD dans des modèles in vitro et in vivo de MA induite par la forme oligomère du bêta-amyloïde (A␤), qui agit directement sur la neuro-inflammation dépendante de la microglie et résulte en dommages neuronaux et en déficience cognitive. Le CHD de 0,1 a` 100 g·mL−1 protégeait significativement les cellules PC12 et les cellules primaires d'hippocampe de rat de la toxicité de l'oligomère A␤1–42. De plus, le CHD de 1 a` 10 ␮g·mL−1 inhibait dans les cellules de la microglie, la production d'oxyde nitrique, du facteur nécrosant des tumeurs-␣ et d'interleukine-1␤ induite par l'oligomère A␤1–42. Dans un modèle in vivo de MA, l'administration de CHD (50 mg·(kg de masse corporelle)−1, 5 jours, per oral) inhibait l'activation des astrocytes et de la microglie dans le giron denté, ainsi que le dommage neuronal dans l'aire CA1 de l'hippocampe ipsilatéral. En outre, le CHD améliorait les déficiences cognitives induites par la toxicité de l'oligomère A␤1–42. Ces résultats démontrent les effets neuro-protecteurs du CHD a` travers l'inhibition de la neuro-inflammation dépendante de la microglie dans des modèles de MA induits in vitro et in vivo par la toxicité de l'oligomère A␤1–42. [Traduit par la Rédaction] Mots-clés : Chunghyuldan, forme oligomère du ␤-amyloïde, maladie d'Alzheimer, neuro-inflammation.

Introduction Alzheimer's disease (AD) accounts for 60%–70% of dementias and affects

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

Microglia-mediated inflammation is a major pathological mechanism contributing to Alzheimer's disease (AD), and has been proposed as a potential thera...
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