title: The effects of C-glycosylation of luteolin on its antioxidant, anti-Alzheimer's disease, anti-diabetic, and anti-inflammatory activities.
abstract: To investigate the effect of C-glycosylation at different positions of luteolin, the structure-activity relationships of luteolin and a pair of isomeric C-glycosylated derivatives orientin and isoorientin, were evaluated. We investigated the effects of C-glycosylation on the antioxidant, anti-Alzheimer's disease (AD), anti-diabetic and anti-inflammatory effects of luteolin and its two C-glycosides via in vitro assays of peroxynitrite (ONOO(-)), total reactive oxygen species (ROS), nitric oxide (NO), 1,1-diphenyl-2-picrylhydraxyl (DPPH), aldose reductase, protein tyrosine phosphatase 1B (PTP1B), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor cleaving enzyme 1 (BACE1), and cellular assays of NO production and inducible nitric oxide synthase (iNOS)/cyclooxygenase-2 expression in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Of the three compounds, isoorientin showed the highest scavenging activity against DPPH, NO, and ONOO(-), while luteolin was the most potent inhibitor of ROS generation. In addition, luteolin showed the most potent anti-AD activity as determined by its inhibition of AChE, BChE, and BACE1. With respect to anti-diabetic effects, luteolin exerted the strongest inhibitory activity against PTP1B and rat lens aldose reductase. Luteolin also inhibited NO production and iNOS protein expression in LPS-stimulated macrophages, while orientin and isoorientin were inactive at the same concentrations. The effects of C-glycosylation at different positions of luteolin may be closely linked to the intensity and modulation of antioxidant, anti-AD, anti-diabetic, and anti-inflammatory effects of luteolin and its C-glycosylated derivatives.
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, Pusan, 608-737, Republic of Korea, choijs@pknu.ac.kr.
authors.forename: Jae Sue
authors.initials: JS
authors.lastname: Choi
authors.forename: Md Nurul
authors.initials: MN
authors.lastname: Islam
authors.forename: Md Yousof
authors.initials: MY
authors.lastname: Ali
authors.forename: Young Myeong
authors.initials: YM
authors.lastname: Kim
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Hee Sook
authors.initials: HS
authors.lastname: Sohn
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Jung
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000544:Alzheimer Disease / Q000188:drug therapy*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors; D001713:Biphenyl Compounds / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D005960:Glucosides / Q000494:pharmacology* / Q000627:therapeutic use; D006031:Glycosylation; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D066298:In Vitro Techniques; D047311:Luteolin / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D030421:Peroxynitrous Acid / Q000378:metabolism; D010851:Picrates / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001713:Biphenyl Compounds; D002800:Cholinesterase Inhibitors; D052246:Cyclooxygenase 2 Inhibitors; D005419:Flavonoids; D005960:Glucosides; D007004:Hypoglycemic Agents; D010851:Picrates; D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C057912:homoorientin; C004931:1,1-diphenyl-2-picrylhydrazyl; D000449:Aldehyde Reductase; D052247:Nitric Oxide Synthase Type II; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat; C065886:orientin; D047311:Luteolin