A modified preparation (LMK03) of the oriental medicine Jangwonhwan reduces Abeta(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: Alzheimer Disease - drug therapy; Alzheimer Disease - physiopathology; Amyloid beta-Peptides - drug effects; Amyloid beta-Peptides - metabolism; Angelica - chemistry; Animals; Brain - drug effects; Brain - pathology; Cell Line, Tumor; Disease Models, Animal; Female; Gene Expression Regulation - drug effects; Hippocampus - drug effects; Hippocampus - metabolism; Humans; Male; Medicine, East Asian Traditional; Mice; Mice, Transgenic; Neuroblastoma - drug therapy; Neuroblastoma - pathology; Oxidative Stress - drug effects; Peptide Fragments - drug effects; Peptide Fragments - metabolism; Plant Extracts - pharmacology; Poria - chemistry
• ISSN: 1872-7573

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. It was investigated whether a further reduction of Jangwonhwan (LMK03-Jangwonhwan) retains the potency to suppress the AD-like pathology. 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 Abeta-induced cell death, and the Abeta accumulation and plaque deposition in the brain. In vitro study with SH-SY5Y neuroblastoma cells showed that LMK03-Jangwonhwan could protect from cytotoxicity induced by hydrogen peroxide or oligomeric Abeta(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 Abeta(1-42)and Abeta(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. 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.