A modified preparation (LMK03) of the oriental medicine Jangwonhwan reduces Aβ1–42 level in the brain of Tg-APPswe/PS1dE9 mouse model of Alzheimer disease

Ethnopharmacological relevanceThe 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 studyIt was investigated whether a further reduction of Jangwonhwan (LMK03-Jangwonhwan) retains the potency to suppress the AD-like pathology.Materials and MethodsThe 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 Aβ-induced cell death, and the Aβ accumulation and plaque deposition in the brain.ResultsIn vitro study with SH-SY5Y neuroblastoma cells showed that LMK03-Jangwonhwan could protect from cytotoxicity induced by hydrogen peroxide or oligomeric Aβ1–42. 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 Aβ1–42 and Aβ1–40 levels and β-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.ConclusionsThese 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.

LMK03-Jangwonhwan, a modified recipe of traditional Jangwonhwan consisting of white Poria cocos (Schw.) Wolf and Angelica gigas Nakai, has the potency to inhibit Aβ level in the brain of Tg-APPswe/PS1dE9 mouse model of Alzheimer disease.Figure optionsDownload as PowerPoint slide