title: Antidiabetic complications and anti-Alzheimer activities of sophoflavescenol, a prenylated flavonol from Sophora flavescens, and its structure-activity relationship.
abstract: It was previously reported that prenylated flavonols from Sophora flavescens are inhibitors of rat lens aldose reductase (RLAR), human recombinant aldose reductase (HRAR), advanced glycation endproducts (AGE), β-secretase (BACE1) and cholinesterases (ChE). Based upon structure-activity relationships, 3,4'-dihydroxy flavonols with a prenyl or lavandulyl group substitution at the C-8 position, and a hydroxy group at the C-5, are important for such inhibition. In our ongoing study to isolate active principles from S. flavescens by an activity-guided isolation procedure, further detailed phytochemical investigations of the CH(2)Cl(2) fraction were conducted via repeated chromatography over silica gel and Sephadex LH-20 columns. This ultimately resulted in the isolation of a promising active sophoflavescenol with higher inhibitory activities among the current prenylated flavonols isolated from S. flavescens against RLAR, HRAR, AGE, BACE1 and ChEs. The results further support that 3,4'-dihydroxy flavonols with a prenyl or lavandulyl substitution at the C-8 position and a methoxy group at C-5 represent a new class of RLAR, HRAR and AGE inhibitors. Nevertheless, the C-5 hydroxyl group of prenylated flavonoids is important for inhibition of BACE1 and ChEs, indicating that the hydroxyl group at C-5 might be the main contributor to the augmentation and/or modification of prenylated flavonol activity.
authors.affiliation: Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju, Republic of Korea.
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Jung
authors.forename: Seong Eun
authors.initials: SE
authors.lastname: Jin
authors.forename: Jun-Seong
authors.initials: JS
authors.lastname: Park
authors.forename: Jae Sue
authors.initials: JS
authors.lastname: Choi
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000544:Alzheimer Disease / Q000188:drug therapy; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D000818:Animals; D002802:Cholinesterases / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005419:Flavonoids / Q000008:administration & dosage / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors; D006801:Humans; D020128:Inhibitory Concentration 50; D008519:Medicine, Traditional; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D054876:Prenylation; D051381:Rats; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D029909:Sophora / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D017127:Glycation End Products, Advanced; D010936:Plant Extracts; D011994:Recombinant Proteins; C117237:sophoflavescenol; D000449:Aldehyde Reductase; D002802:Cholinesterases; D053829:Amyloid Precursor Protein Secretases