title: In vitro BACE1 inhibitory activity of geraniin and corilagin from Geranium thunbergii.
abstract: Generation of amyloid β peptide through the proteolytic process of amyloid precursor protein by β-secretase and γ-secretase is a main casual factor of Alzheimer's disease, since amyloid β peptide is a major and crucial component of senile plaques in Alzheimer's disease brains. In the process of searching for β-secretase inhibitors from natural resources, the EtOAc soluble fraction of Geranium thunbergii exhibited significant β-secretase inhibitory activity. Two compounds, geraniin and corilagin, isolated from the most active EtOAc fraction of G. thunbergii, exhibited predominant inhibition against β-secretase with IC₅₀ values of 4.0 × 10⁻⁶ M and 3.4 × 10⁻⁵ M, respectively. Dixon plot of geraniin and corilagin demonstrated that the β-secretase inhibition was noncompetitive with the substrate, thus clearly suggesting that these compounds might bind either to the β-secretase subsites or to another regulatory domain with Ki values of 2.8 × 10⁻⁶ M and 7.9 × 10⁻⁵ M, respectively. Both compounds exhibited no significant inhibition against α-secretase and other serine proteases including trypsin and chymotrypsin, showing that they were relatively specific and selective inhibitors of β-secretase. These novel findings suggest that geraniin and corilagin from G. thunbergii may be effective therapeutic agents for further drug development in Alzheimer's disease.
authors.affiliation: Department of Food Science and Nutrition, Dong-A University, Busan, Korea.
authors.forename: Kumju
authors.initials: K
authors.lastname: Youn
authors.forename: Mira
authors.initials: M
authors.lastname: Jun
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D031315:Geranium / Q000737:chemistry*; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D005960:Glucosides; D047348:Hydrolyzable Tannins; C024603:Geraniin; C049096:corilagin