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.

Kinetics and molecular docking studies of cholinesterase inhibitors derived from water layer of Lycopodiella cernua (L.) Pic. Serm. (II)

“…The BACE1 inhibitory activity of each sample was expressed in terms of the IC 50 value (µM required to inhibit the proteolysis of BACE1 by 50%), as calculated from the log-dose inhibition curve. Quercetin was used as a positive control [9].…”

Sphingosylphosphorylcholine Attenuated β–Amyloid Production by Reducing BACE1 Expression and Catalysis in PC12 Cells

“…In PC12 neuronal cell model, SPC significantly inhibited Ab generation by suppressing both activity and gene expression of BACE1. The inhibitory activity of SPC on BACE1 was more potent than the botanical compounds like diterpenoids, bis(7)-tacrine, prenylated flavonoids, and coptidis Rhizoma alkaloids [38,[41][42][43].…”

“…There are many botanicals or chemicals under biological testing [38][39][40][41][42][43][44]. Bioactive LPs modulate a neural cell differentiation, inflammation, apoptosis and intracellular trafficking in the plasma and APP metabolism of BACE1 [13,45,46].…”

Terpenoid composition and the anticancer activity of Acanthopanax trifoliatus

“…By comparison of their NMR data to those reported in the literature, the structures of these compounds were identified as impressic acid (3) (Kuo et al 2002), 3a,11a-dihydroxy-lup-20(29)-en-23-al-28-oic acid (4) (Chang et al 1999), 3a-hydroxy-lup-20(29)-en-23,28-dioic acid (5) (Chang et al 1998), 3a,11a-dihydroxy-lup-20(29)-en-23,28-dioic acid (6) (Lischewski et al 1984), 3a-hydroxylup-20(29)-en-30-ol-23,28-dioic acid (7) (Wanas et al 2010), ent-kaur-15-en-17-al-19-oic acid (8) (Harrigan et al 1994), 17-hydroxy-16a-ent-kauran-19-oic acid (9) (Duan et al 1999), 16a-hydroxy-ent-kauran-19-oic acid (10) (Duan et al 1999), 13-epi-ent-manoyloxide-19-oic acid (11) (Zdero et al 1992), ent-kaur-16-en-19-al (12) (Catalano et al 1993), ent-kaur-16-en-19-oic acid (13) (Catalano et al 1993), 18-nor-ent-kaur-16-ene-4b-ol (14) (Jung et al 2009) and ent-19-hydroxy-13-epi-manoyl oxide (15) (Fraga et al 1989) (Fig. 1), respectively.…”