Oriental medicine Jangwonhwan reduces Aβ(1-42) level and β-amyloid deposition in the brain of Tg-APPswe/PS1dE9 mouse model of Alzheimer disease

Abstract

Ethnopharmacological relevance: Jangwonhwan, a boiled extract of 12 medicinal plants/mushroom including Korean red ginseng (Panax ginseng C.A. Meyer), has been prescribed for patients with cognitive dysfunction and are believed to induce brain activity enhancement, provide light sedation, and facilitate sound sleep. Aim of the study: The present study was carried out to investigate whether Jangwonhwan has a beneficial effect on the brain of Alzheimer disease. Materials and methods: The transgenic mice of Alzheimer disease, Tg-APPswe/PS1dE9, were fed a modified recipe of Jangwonhwan consisting of a boiled extract of 7 herbs/mushroom (called LMK02-Jangwonhwan) at 400 mg/kg/day of dose for 3 months from 4.5 months of age. Immunohistological and ELISA analyses were used to assess the Aβ accumulation and plaque deposition in the brain. Other in vitro and in vivo works were performed to understand the underlying mechanism. Results: LMK02-Jangwonhwan notably reduced Aβ(1-42) and Aβ(1-40) levels, concomitantly with a reduction of plaque deposition, in the brain of Tg-APPswe/PS1dE9 mice. LMK02-Jangwonhwan partially suppressed oxidative stress accumulation, and prevented the down-regulation of phospho-CREB and calbindin typically seen in the hippocampus of AD-like brains. In vitro study with SH-SY5Y neuroblastoma cells showed that LMK02-Jangwonhwan inhibited oxidative stress and Aβ-induced neurotoxicity. Conclusion: The present study suggests that LMK02-Jangwonhwan confers a therapeutic potential to ameliorate AD-like pathology in the brain of Tg-APPswe/PS1dE9 mice. © 2010 Elsevier Ireland Ltd.