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[P2–135]: AN HERBAL EXTRACT (HE238) SUPPRESSES AMYLOID‐β42‐ELICITED NEUROTOXICITY IN MICE THROUGH ACTIVATION OF AUTOPHAGY
Author(s) -
Liao YungFeng,
Chen Rita,
Huang ChangJen
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.785
Subject(s) - autophagy , neurotoxicity , intracellular , pharmacology , morris water navigation task , medicine , chemistry , microbiology and biotechnology , hippocampus , biology , toxicity , biochemistry , apoptosis
Background:Alzheimer’s disease (AD) is the most prevalent form of dementia in the elderly in the world. Compelling evidence has shown that dysfunction in autophagic clearance of amyloid-b (Ab) and Tau could significantly contribute to the manifestation of the two most distinctive neuropathological hallmarks, the extracellular deposition of amyloid plaques and the intracellular aggregation of fibrillary tangles, in AD brain. We thus seek to identify novel autophagy-enhancing agents from herbal extracts that can reduce Ab-elicited neurotoxicity and cognitive impairment through promoting the autophagic clearance of Ab.Methods:We established a cell-based Renilla luciferase reporter assay for p62-dependent selective autophagy, which was employed to screen a collection of 650 distinct herbal extracts. Effective herbal extracts that exhibit autophagy-inducing activity in lowering the p62-dependent Renilla luciferase signal, indicative of autophagy activation, were further pursued. The autophagy-inducing potency was validated in the secondary confirmation assay, in which the conversion of LC3-I to LC3-II and the level of p62 were determined. An intracerebral Ab42-injection mouse model of AD was employed to assess the biological efficacy of effective herbal extracts on cognitive improvement. Results:Our data demonstrated that an herbal extract (HE238) can effectively induce autophagy by promoting the LC3-I to LC3-II conversion and the clearance of p62 in cellular models. Oral administration of HE238 to an Ab42-injection mouse model of AD for 2 months can significantly improves the cognitive function of the AD mice by Morris water maze test. Biochemical analysis of brain homogenates derived from HE238-treated animals revealed a significant increase in autophagic activity and neuronal viability. Conclusions:The present findings suggest that the active ingredients of HE238 could contain an enormous resource for AD-alleviating agents.