title: In vitro neuroprotective activities of compounds from Angelica shikokiana Makino.
abstract: Angelica shikokiana is widely marketed in Japan as a dietary food supplement. With a focus on neurodegenerative conditions such as Alzheimer's disease, the aerial part was extracted and through bio-guided fractionation, fifteen compounds [α-glutinol, β-amyrin, kaempferol, luteolin, quercetin, kaempferol-3-O-glucoside, kaempferol-3-O-rutinoside, methyl chlorogenate, chlorogenic acid, hyuganin E, 5-(hydroxymethyl)-2-furaldehyde, β-sitosterol-3-O-glucoside, adenosine (isolated for the first time from A. shikokiana), isoepoxypteryxin and isopteryxin] were isolated. Isolated compounds were evaluated for in vitro neuroprotection using acetylcholine esterase inhibitory, protection against hydrogen peroxide and amyloid β peptide (Aβ25-35)-induced neurotoxicity in neuro-2A cells, scavenging of hydroxyl radicals and intracellular reactive oxygen species and thioflavin T assays. Quercetin showed the strongest AChE inhibition (IC50 value = 35.5 µM) through binding to His-440 and Tyr-70 residues at the catalytic and anionic sites of acetylcholine esterase, respectively. Chlorogenic acid, its methyl ester, quercetin and luteolin could significantly protect neuro-2A cells against H2O2-induced neurotoxicity and scavenge hydroxyl radical and intracellular reactive oxygen species. Kaempferol-3-O-rutinoiside, hyuganin E and isoepoxypteryxin significantly decreased Aβ25-35-induced neurotoxicity and Th-T fluorescence. To the best of our knowledge, this is the first report about neuroprotection of hyuganin E and isoepoxypteryxin against Aβ25-35-induced neurotoxicity.
authors.affiliation: Division of Systematic Forest and Forest Products Sciences, Department of agroenvironmental sciences, Faculty of Agriculture, Graduate School of Kyushu University, Fukouka 812-8581, Japan. dramiramera@yahoo.com.|Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. dramiramera@yahoo.com.
authors.forename: Amira
authors.initials: A
authors.lastname: Mira
authors.affiliation: Department of Bioscience & Biotechnology, Graduate School of Bioresource and Bioenvironmental sciences, Kyushu University, Fukouka 812-8581, Japan. shuntaro@grt.kyushu-u.ac.jp.
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Yamashita
authors.affiliation: Department of Bioscience & Biotechnology, Graduate School of Bioresource and Bioenvironmental sciences, Kyushu University, Fukouka 812-8581, Japan. katakura@grt.kyushu-u.ac.jp.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Katakura
authors.affiliation: Division of Systematic Forest and Forest Products Sciences, Department of agroenvironmental sciences, Faculty of Agriculture, Graduate School of Kyushu University, Fukouka 812-8581, Japan. shimizu@agr.kyushu-u.ac.jp.
authors.forename: Kuniyoshi
authors.initials: K
authors.lastname: Shimizu
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity; D029969:Angelica / Q000737:chemistry*; D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D006861:Hydrogen Peroxide / Q000633:toxicity; D066298:In Vitro Techniques; D007564:Japan; D051379:Mice; D009447:Neuroblastoma / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity; D035261:Plant Components, Aerial / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology*; D011794:Quercetin / Q000302:isolation & purification / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); D011794:Quercetin; D006861:Hydrogen Peroxide