A modified preparation (LMK03) of the oriental medicine Jangwonhwan reduces Ab sub(1-42) level in the brain of Tg-APPswe/PS1dE9 mouse model of Alzheimer disease

• Published in: Journal of ethnopharmacology 2010-08, Vol.130 (3), p.578-585
• Main Authors: Seo, Ji-Seon, Jung, Eun-Young, Kim, Ji-Hye, Lyu, Yeoung-Su, Han, Pyung-Lim, Kang, Hyung-Won
• Format: Article
• Language: English
• Subjects: Angelica; Poria
• ISSN: 0378-8741
• DOI: 10.1016/j.jep.2010.05.055

Ethnopharmacological relevance - The oriental medicine Jangwonhwan, which is a boiled extract of 12 medicinal herbs/mushroom, has been prescribed for patients with cognitive dysfunction. Recently, a modified recipe of Jangwonhwan (LMK02-Jangwonhwan) consisting of seven medicinal plants/mushroom, was shown to have a therapeutic potential to ameliorate AD-like pathology. Aim of the study - It was investigated whether a further reduction of Jangwonhwan (LMK03-Jangwonhwan) retains the potency to suppress the AD-like pathology. Materials and Methods - The transgenic mice of Alzheimer disease, Tg-APPswe/PS1dE9, were fed LMK03-Jangwonhwan consisting of two of the herbs, white Poria cocos (Schw.) Wolf and Angelica gigas Nakai, which could protect the AD-like pathology at 300 mg/kg/day of dose for 3 months. In vitro cell biological study, immunohistological and ELISA (enzyme-linked immunosorbent assay) analyses were used to assess its neuroprotective effects against Ab-induced cell death, and the Ab accumulation and plaque deposition in the brain. Results - In vitro study with SH-SY5Y neuroblastoma cells showed that LMK03-Jangwonhwan could protect from cytotoxicity induced by hydrogen peroxide or oligomeric Ab sub(1-42). Tg-APPswe/PS1dE9 mice were administered LMK03-Jangwonhwan at 300 mg/kg/day for 3 months from 4.5 months of age. Immunohistological and ELISA analyses showed that LMK03-Jangwonhwan partially reduced Ab sub(1-42) and Ab sub(1-40) levels and b-amyloid plaque deposition in the brain of Tg-APPswe/PS1dE9 mice. However, LMK03-Jangwonhwan poorly suppressed accumulation of reactive oxidative stress in the hippocampus of Tg-APPswe/PS1dE9 mice and inefficiently improved the expression of phospho-CREB and calbindin, the cellular factors that were down-regulated in AD-like brains. Conclusions - These results suggest that LMK03-Jangwonhwan has a potency to inhibit AD-like pathology at a detectable level, but LMK03 is not likely to retain the major ability of LMK02-Jangwonhwan to modify AD pathology in several AD-related molecular parameters.