Cholinesterase and BACE1 inhibitory diterpenoids from Aralia cordata.
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.
Jung
Hyun Ah
HA
Division of Food Science and Biotechnology, Pukyong National University, Busan, Korea.
Lee
Eun Ju
EJ
Kim
Ju Sun
JS
Kang
Sam Sik
SS
Lee
Je-Hyun
JH
Min
Byung-Sun
BS
Choi
Jae Sue
JS
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
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