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

作者：Seo Ji Seon; Jung Eun Young; Kim Ji Hye; Lyu Yeoung Su; Han Pyung Lim; Kang Hyung Won^*

来源：Journal of Ethnopharmacology, 2010, 130(3): 578-585.

DOI：10.1016/j.jep.2010.05.055

• Oriental medicine
• Alzheimer disease
• A beta
• Plaque
• LMK03-Jangwonhwan
• White Poria cocos (Schw.) Wolf
• Angelica gigas Nakai

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 A beta-induced cell death, and the A beta 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 A beta(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 A beta(1-42) and A beta(1-40) levels and beta-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.

• 出版日期2010-8-9