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Cholinesterase and BACE1 inhibitory diterpenoids from Aralia cordata

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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-4β-ol (3); 18-nor-ent-kaur-16-ene-4β-ol (4); ent-pimara-8(14),15-diene-19-ol (5); 7α-hydroxy-ent-pimara-8(14),15-diene-19-oic acid (6); 7β-hydroxy-ent-pimara-8(14),15-diene-19-oic acid (7); ent-pimar-15-en-8α,19-diol (8); 7-oxo-ent-pimara-8(14),15-diene-19-oic acid (9); 16α-hydroxy-17-isovaleroyloxy-ent-kauran-19-oic acid (10); 17-hydroxy-ent-kaur-15-en-19-oic acid (11); 15α,16α-epoxy-17-hydroxy-ent-kauran-19-oic acid (12); 16α,17-dihydroxy-ent-kauran-19-oic acid (13); and 16α-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 β-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 IC50 value of 7.58 µM, followed by 3, 13, 11, 2, and 10. Compounds 9∼11 exhibited good BACE1 inhibitory activities with IC50 values of 18.58∼24.10 µM. However, 11 showed marginal AChE inhibitory effect, and all compounds tested showed no scavenging activities on ONOO− and NO· at a concentration of 100 µM.

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Authors and Affiliations

  1. Division of Food Science and Biotechnology, Pukyong National University, Busan, 608-737, Korea

    Hyun Ah Jung & Jae Sue Choi

  2. Natural Products Research Institute and College of Pharmacy, Seoul National University, Seoul, 151-742, Korea

    Eun Ju Lee, Ju Sun Kim & Sam Sik Kang

  3. College of Oriental Medicine, Dongguk University, Gyeongju, 780-714, Korea

    Je-Hyun Lee

  4. College of Pharmacy, Catholic University of Daegu, Gyeongbuk, 712-702, Korea

    Byung-Sun Min

  5. Blue-Bio Industry RIC, 995 Eomgwangno Busanjin-gu, Busan, 614-714, Korea

    Jae Sue Choi

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  1. Hyun Ah Jung
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Jung, H.A., Lee, E.J., Kim, J.S. et al. Cholinesterase and BACE1 inhibitory diterpenoids from Aralia cordata . Arch. Pharm. Res. 32, 1399–1408 (2009). https://doi.org/10.1007/s12272-009-2009-0

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  • DOI: https://doi.org/10.1007/s12272-009-2009-0

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