title: Cholinesterase and BACE1 inhibitory diterpenoids from Aralia cordata.
abstract: Fourteen diterpenes were isolated from the n-hexane fraction of the roots of Aralia cordata (syn. = A. continentalis). Through spectroscopy, the chemical structures were determined as: ent-pimara-8(14),15-diene-19-oic acid (1); ent-kaur-16-en-19-oic-acid (2); 18-nor-ent-pimara-8(14),15-diene-4beta-ol (3); 18-nor-ent-kaur-16-ene-4beta-ol (4); ent-pimara-8(14),15-diene-19-ol (5); 7alpha-hydroxy-ent-pimara-8(14),15-diene-19-oic acid (6); 7beta-hydroxy-ent-pimara-8(14),15-diene-19-oic acid (7); ent-pimar-15-en-8alpha,19-diol (8); 7-oxo-ent-pimara-8(14),15-diene-19-oic acid (9); 16alpha-hydroxy-17-isovaleroyloxy-ent-kauran-19-oic acid (10); 17-hydroxy-ent-kaur-15-en-19-oic acid (11); 15alpha,16alpha-epoxy-17-hydroxy-ent-kauran-19-oic acid (12); 16alpha,17-dihydroxy-ent-kauran-19-oic acid (13); and 16alpha-methoxy-17-hydroxy-ent-kauran-19-oic acid (14). Compounds 4, 5, 8, 12, and 14 were first isolated from this plant. The anti-Alzheimer and antioxidant effects of ent-pimarane-type diterpenes 1, 3, 5, 8, and 9, as well as ent-kaurane-type diterpenes 2, 4, and 10-13, were evaluated via beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), peroxynitrite (ONOO(-)), and nitric oxide (NO*) assays. Of the compounds tested, 8 exerted the most effective BChE inhibition with an IC(50) value of 7.58 microM, followed by 3, 13, 11, 2, and 10. Compounds 9-11 exhibited good BACE1 inhibitory activities with IC(50) values of 18.58-24.10 microM. However, 11 showed marginal AChE inhibitory effect, and all compounds tested showed no scavenging activities on ONOO(-) and NO* at a concentration of 100 microM.
authors.affiliation: Division of Food Science and Biotechnology, Pukyong National University, Busan, Korea.
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Jung
authors.forename: Eun Ju
authors.initials: EJ
authors.lastname: Lee
authors.forename: Ju Sun
authors.initials: JS
authors.lastname: Kim
authors.forename: Sam Sik
authors.initials: SS
authors.lastname: Kang
authors.forename: Je-Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Byung-Sun
authors.initials: BS
authors.lastname: Min
authors.forename: Jae Sue
authors.initials: JS
authors.lastname: Choi
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D027983:Aralia / Q000737:chemistry*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology; D002802:Cholinesterases / Q000378:metabolism*; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000302:isolation & purification / Q000494:pharmacology*; D005609:Free Radicals / Q000737:chemistry; D009569:Nitric Oxide / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry
chemical_list: D002800:Cholinesterase Inhibitors; D004224:Diterpenes; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D005609:Free Radicals; D009569:Nitric Oxide; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D002802:Cholinesterases; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human