Three lignans isolated from the roots of A. koreanum (Araliaceae), namely eleutheroside E (1), tortoside A (2), and hemiariensin (4), were evaluated for their ability to inhibit NFAT transcription factor. Of these compounds, compound 4, possessing a diarylbutane skeleton, exhibited potent inhibitory activity against NFAT transcription factor (IC50: 36.3 +/- 2.5 microM). However, the activities of 1 (IC50: > 500 microM) and 2 (IC50: 136.1 +/- 9.4 microM), which possess bisaryldioxabicyclooctane skeletons, were lower. As the lignan derivatives of the same skeletons, hinokinin (5) and (-)-yatein (6) with diarylbutane skeletons and (+)-syringaresinol (3) with a bisaryldioxabicyclooctane skeleton were also studied for their inhibitory effects on NFAT transcription factor.
Two triterpenoids (1,4) and two triterpenoid glycosides (2,3) were isolated from the root of Acanthopanax koreanum (Araliaceae). Their structures were identified as impressic acid (1), acankoreoside A (2), 3-epi-betulinic acid 28-O-[alpha-L-rhamnopyranosyl(1 --> 4)-beta-D-glucopyranosyl(1 --> 6)]-beta-D-glucopyranosyl] ester (3), and ursolic acid (4) by physicochemical and spectroscopic methods. Of these compounds, impressic acid (1) exhibited a potent inhibitory activity against NFAT transcription factor (IC50: 12.65 microM).
Five known kaurane type diterpenoids, 16alphaH,17-isovaleryloxy-ent-kauran-19-oic acid (1), 16alpha-hydroxy-17-isovaleryloxy-ent-kauran-19-oic acid (2), paniculoside-IV (3), 16alpha-hydroxy-ent-kauran-19-oic acid (4), and ent-kaur-16-en-19-oic acid (5) were isolated from the root of Acanthopanax koreanum by repeated column chromatography and reversed phase preparative HPLC. The structures of these compounds were established from physicochemical and spectral data. Among the isolated compounds 16alphaH,17-isovaleryloxy-ent-kauran-19-oic acid (1) showed potent inhibitory activity (IC50 value, 16.2 uM) on TNF-alpha secretion from HMC-1, a trypsin-stimulated human leukemic mast cell line.
The transcription factor called the "nuclear factor of activated T cells" (NFAT) is a cytoplasmic protein that is activated by the stimulation of the cell surface receptors coupled to Ca 2ϩ mobilization. The Ca 2ϩ activated phosphatase, calcineurin, dephosphorylates this NFAT protein, and promotes their nuclear translocation and activation.1) However, the excessive activation of NFAT provokes immunopathological reactions including autoimmunity, transplant rejection and inflammation.2) Therefore, it is expected that modulating the NFAT transcription factor will be useful in treating immune diseases. A high-affinity calcineurin-binding peptide 3) and 3,5-bis(trifluoromethyl)pyrazoles 4) were reported to be regulators of the NFAT transcription factor. Recently, lignans were isolated from Schisandra chinensis 5) and phthalides and an acetylene component were isolated from Cnidium officinale, 6) which are substances for regulating the NFAT transcription factor isolated from several medicinal plants.In an ongoing study for screening regulators from medicinal plants, potent activity was found in the MeOH extract of the Liquidambar formosana fruit (Hamamelidaceae) which has been used as an analgesic, diuretic and anticonvulsant in Oriental medicine. 7) Four oleanane triterpenoids which had not been reported as NFAT transcription factor regulators were isolated by activity-guided fractionation from this plant. Herein, we report the inhibitory activity of these compounds against the NFAT transcription factor. RESULTS AND DISCUSSIONThis study forms part of an ongoing study screening several medicinal plants for inhibitory activity against NFAT transcription factor. The results showed that the MeOH extract of L. formosana exhibited high activity (IC 50 : 4.67Ϯ0.61 mg/ml). The MeOH extract of L. formosana was suspended in water and consecutively partitioned with hexane, EtOAc and BuOH. The EtOAc fraction exhibited strong activity (IC 50 : 4.31Ϯ0.33 mg/ml), and activity-guided separation yielded four oleanane triterpenoids, liquidambaric acid (1), oleanolic acid (2), 3a-acetoxy-25-hydroxy-olean-12-en-28-oic acid (3), and lantanolic acid (5), as shown in Fig. 1. Of these compounds, compound 3 exhibited the strongest inhibitory activity against the NFAT transcription factor (IC 50 : 4.63Ϯ0.22 mM). However, the activity of 3 (IC 50 : 2.38 mg/ml) was similar to that of the EtOAc fraction. This fact indicates that other strong inhibitors may be present in minor constituents of the EtOAc fraction. Compound 5, which was isolated for the first time from L. formosana, showed moderate inhibitory activity against the NFAT transcription factor (IC 50 : 12.62Ϯ0.17 mM). However, compounds 1 and 2 did not have any inhibitory activity with IC 50 values over 50 mM (cell viability: Ͻ65%). From the structure activity relationship, compounds 1 and 2, which lack one oxy methylene group at C-25, had weak activity (IC 50 : Ͼ50 mM) on the NFAT transcription factor (Table 1). However, compounds 3 and 5 with this group at C-25 exhibited high inhibitor...
A new pimarane-type diterpene compound, acanthokoreoic acid A together with three known compounds, acanthoic acid, acanthol, and sumogaside were isolated from a CH(2)Cl(2) fraction of Acanthopanax koreanum by repeated column chromatography and reversed phase preparative HPLC. Acanthoic acid was isolated in high yields and showed potent inhibitory activity on the IL-8 secretion of the TNF-alpha-stimulated human colon adenocarcinoma cell line HT-29 and on the TNF-alpha secretion of the trypsin-stimulated human leukemic mast cell line HMC-1.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.