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.
BACKGROUND
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.


OBJECTIVE
It was investigated whether a further reduction of Jangwonhwan (LMK03-Jangwonhwan) retains the potency to suppress the AD-like pathology.


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 Abeta-induced cell death, and the Abeta 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 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.


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.
Seo
Ji-Seon
JS
Department of Chemistry & Nano Science, Ewha Womans University, Seoul, Republic of Korea.
Jung
Eun-Young
EY
Kim
Ji-Hye
JH
Lyu
Yeoung-Su
YS
Han
Pyung-Lim
PL
Kang
Hyung-Won
HW
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000187:drug effects* / Q000378:metabolism; D029969:Angelica / Q000737:chemistry; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D008518:Medicine, East Asian Traditional; D051379:Mice; D008822:Mice, Transgenic; D009447:Neuroblastoma / Q000188:drug therapy / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D055441:Poria / Q000737:chemistry
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010936:Plant Extracts; C075222:amyloid beta-protein (1-42)