Neuroprotective effects of an herbal medicine, Yi-Gan San on MPP+/MPTP-induced cytotoxicity in vitro and in vivo

作者 Doo, Ah-Reum; Kim, Seung-Nam; Park, Ji-Yeon; Cho, Ki Ho; Hong, Jongki; Eun-Kyung, Kim; Moon, Sang Kwan; Jung, Woo Sang; Lee, Hyejung; Jung, Jae Han; Park, Hi-Joon

期刊 JOURNAL OF ETHNOPHARMACOLOGY , SEP 15 2010,2:131

DOI 10.1016/j.jep.2010.07.008 PubMed 20633628

摘要 Ethnopharmacological relevance. A traditional herb. Yi-Gan San, has been widely used for the management of neurodegenerative disorders in traditional East Asian Medicine.Aim of the study The present study investigated the neuroprotective effects of Yi-Gan San in 1-methyl-4-phenylpyridine/1-methyl-4-phenyl-1,2,3,6-tetrahydropyndine-induced cytotoxicity in vitro and in vivo and sought to clarify its underlying mechanisms Materials and methods The effect of Yi-Gan San on 1-methyl-4-phenylpyridine was measured in terms of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays, caspase-3 activity, and western blot analysis of phosphorylated Akt, one of the survival-related signaling proteins in SH-SY5Y cells The effects of Yi-Gan San were also confirmed in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonian mouse model using a rotarod test and tyrosine hydroxylase-immunolustochemistryResults: Pretreatment of Yi-Gan San with 1-methyl-4-phenylpyridine showed a significant protective effect on SH-SY5Y cells and significantly decreased the level of caspase-3 activity compared to the values for the 1-methyl-4-phenylpyridine-treated cells. This process increased the protein expressions of phosphorylated Akt. and an inhibitor of phosphatidylinositol 3-kinase (PI3K)/Akt, LY294002, significantly decreased this protective effect of Yi-Gan San In the mouse Parkinson''s disease model, treatment with Yi-Gan San also significantly improved motor functioning and prevented dopaminergic loss related to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine challengeConclusion: Using both in vitro and in vivo methods, this study revealed that Yi-Gan San has neuroprotective effects and rescues dopaminergic neurons from 1-methyl-4-phenylpyridine/1-methyl4-phenyl-1,2.3,6-tetrahydropyridine toxicity, possibly via the PI3K/Akt pathway (C) 2010 Elsevier Ireland Ltd All rights reserved.