title: Effects of C-glycosylation on anti-diabetic, anti-Alzheimer's disease and anti-inflammatory potential of apigenin.
abstract: Apigenin has gained particular interests in recent years as a beneficial and health promoting agent because of its low intrinsic toxicity. Vitexin and isovitexin, naturally occurring C-glycosylated derivatives of apigenin, have been known to possess potent anti-diabetic, anti-Alzheimer's disease (anti-AD), and anti-inflammatory activities. The present study was designed to investigate the anti-diabetic, anti-AD, and anti-inflammatory potential of apigenin and its two C-glycosylated derivatives, vitexin and isovitexin by in vitro assays including rat lens aldose reductase (RLAR), human recombinant aldose reductase (HRAR), advanced glycation endproducts (AGEs), protein tyrosine phosphatase 1B (PTP1B), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-site amyloid precursor (APP) cleaving enzyme 1 (BACE1), and nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Among them, isovitexin was found as the most potent inhibitor against RLAR, HRAR, AGE, AChE, and BChE while vitexin showed the most potent PTP1B inhibitory activity. Despite the relatively weak anti-diabetic and anti-AD potentials, apigenin showed powerful antiinflammatory activity by inhibiting NO production and iNOS and COX-2 expression while vitexin and isovitexin were inactive. Therefore, it could be speculated that C-glycosylation of apigenin at different positions might be closely linked to relative intensity of anti-diabetic, anti-AD, and anti-inflammatory potentials.
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, Republic of Korea. Electronic address: choijs@pknu.ac.kr.
authors.forename: Jae Sue
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Md Nurul
authors.initials: MN
authors.lastname: Islam
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Md Yousof
authors.initials: MY
authors.lastname: Ali
authors.affiliation: Department of Food Science and Nutrition, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Eon Ji
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Young Myeong
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju 561-756, Republic of Korea. Electronic address: jungha@jbnu.ac.kr.
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Jung
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D006031:Glycosylation; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D051379:Mice
chemical_list: D000893:Anti-Inflammatory Agents; D007004:Hypoglycemic Agents; D047310:Apigenin
keywords: 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine hydrochloride; 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide; 5,5′-dithiobis [2-nitrobenzoic acid]; ACh; AChE; AD; AGEs; AMT; APP; AR; ARI; Alzheimer’s disease; Apigenin derivative; Aβ; BACE1; BCh; BChE; COX-2; ChAT; DMEM; DTNB; Diabetic complication; Dulbecco’s Modified Eagle’s Medium; EDTA; FBS; Flavonoid; HRAR; HRP; Inflammation; LPS; MTT; NADPH; NO; NOS; PTP1B; PVDF; RLAR; ROS; acetylcholinesterase; acetylthiocholine iodide; advanced glycation endproducts; aldose reductase; aldose reductase inhibitor; amyloid-β peptides; butyrylcholinesterase; butyrylthiocholine chloride; choline acetyltransferase; cyclooxygenase-2; ethylenediaminetetraacetic acid; fetal bovine serum; horseradish peroxidase; human recombinant aldose reductase; iNOS; inducible nitric oxide synthase; lipopolysaccharide; nitric oxide; nitric oxide synthase; p-nitrophenyl phosphate; pNPP; polyvinylidene fluoride; protein tyrosine phosphatase 1B; rat lens aldose reductase; reactive oxygen species; β-nicotinamide adenine dinucleotide phosphate; β-site amyloid precursor; β-site amyloid precursor cleaving enzyme 1