Junsei Taira

Isolation of C11 Cyclopentenones from Two Didemnid Species, Lissoclinum sp. and Diplosoma sp.

A series of new C11 cyclopentenones 1–7 was isolated, together with four known metabolites 9/10, 12 and 13, from the extract of the didemnid ascidian Lissoclinum sp. The other didemnid ascidian Diplosoma sp. contained didemnenones 1, 2 and 5, and five known metabolites 8–12. The structures of 1–7 were elucidated by spectroscopic analyses. Cytotoxicity of the isolated compounds was evaluated against three human cancer cell lines (HCT116, A431 and A549).

Antioxidant capacity of betacyanins as radical scavengers for peroxyl radical and nitric oxide.

This study was designed to assess the antioxidant capacity of betacyanins as indole derived plant pigments, such as betanin, phyllocactin and betanidin. The antioxidant capacity of the betacyanins was evaluated as an index of radical scavenging ability using the peroxyl radical generating system in the presence of AAPH and NO generating system using NOR3 as an NO donor. The peroxyl radical scavenging capacity was dose-dependent in the low concentration range (25-100 nM). The mol-Trolox equivalent activity/mol compound (mol-TEA/mol-compound) as an index of the antioxidant capacity indicated the following order at 10.70 ± 0.01, 3.31 ± 0.14 and 2.83 ± 0.01 mol-TEA/mol-compound for betanidin, betanin and phyllocactin, respectively. In addition, betacyanins reduced the nitrite-level in the low concentration range of 2.5-20 μM. The IC₅₀ values (μM) of nitrogen radical scavenging activity were 24.48, 17.51 and 6.81 for betanin, phyllocactin and betanidin. ESR studies provided evidence that the compounds directly scavenged NO. These results indicated that betacyanins have a strong antioxidant capacity, particularly betanidin with a catechol group had higher activity than those of the glycoside of betacyanins. This study demonstrated that the betacyanins will be useful as natural pigments to provide defence against oxidative stress.

Cytotoxic Metabolites from the Okinawan Ascidian Diplosoma virens

The unstable isomeric compounds 5-hydroxy-7-prop-2-en-(E)-ylidene-7,7a-dihydro-2H-cyclopenta[b]pyran-6-one (1) and 5-hydroxy-7-prop-2-en-(Z)-ylidene-7,7a-dihydro-2H-cyclopenta[b]pyran-6-one (2), previously described as antimicrobial metabolites from the sponge Ulosa sp., were isolated and identified as major components of the ascidian Diplosoma virens. In this paper, full spectral data for 2 and complete 13C-NMR data for 1, based on 2D NMR measurements, are provided for the first time. Compounds 1 and 2 showed cytotoxity against HCT116 cells (human colorectal cancer cells) by triggering apoptotic cell death.

Isolation of C11 Compounds and a Cyclopropane Fatty Acid from an Okinawan Ascidian, Diplosoma sp.

Pentylphenols 1 and 2, cyclopropane fatty acid 3, and cyclopentenones 4 and 5, were isolated from an ascidian, Diplosoma sp. The structures of 1−5 were determined by spectroscopic analysis and/or synthesis. Compound 1 inhibited the division of fertilized sea urchin eggs and compound 4 showed mild cytotoxity against HCT116 cells (human colorectal cancer cell).

Inhibition of the β-catenin/Tcf signaling by caffeoylquinic acids in sweet potato leaf through down regulation of the Tcf-4 transcription.

Sweet potato leaves contain the highest levels of functional polyphenols. In this study the effects of the sweet potato leaf extract and its contents, such as mono (3, 4, and 5)-caffeoylquinic acid (CQA), di-CQA (4,5-diCQA, 3,5-diCQA, and 3,4-diCQA) and caffeic acid (CA), were evaluated on the β-catenin/Tcf-4 signaling in human colorectal cancer HCT116 cells. The extract and the CQA derivatives inhibited the β-catenin/Tcf-4 signaling, and the inhibition of the di-CQA (with two caffeoyl groups) was higher than that of the mono-CQA (one-caffeoyl group) and CA, suggesting that the caffeoyl structure in the presence of a catechol group plays a significant role in interfering with the β-catenin/Tcf-4 signaling. In addition, the CQA derivatives had no effect on the β-catenin protein expression, but all test compounds inhibited the expression of the Tcf-4 transcription, and the inhibition of the di-CQA derivatives was stronger than those of the mono-CQA derivatives as well as the β-catenin/Tcf-4 transcriptional activity. These compounds can modulate the downstream Wnt signaling pathway, suggesting that sweet potato leaves can be a protective food for colorectal cancer.

Five New Diterpenoids from an Okinawan Soft Coral, Cespitularia sp.

Five new diterpenoids 1–5 were isolated from an Okinawan soft coral, Cespitularia sp., together with the known diterpenoid, alcyonolide (6). New diterpenoid structures were elucidated by spectroscopic methods and by comparison of their NMR data with those of related compounds. Alcyonolide (6) was cytotoxic against HCT 116 cells (IC50 5.85 μM), while these new diterpenoids 1–5 were much less active (IC50 28.2–91.4 μM).

Suppression of nitric oxide production on LPS/IFN-γ-stimulated RAW264.7 macrophages by a novel catechin, pilosanol N, from Agrimonia pilosa Ledeb.

A novel catechin, pilosanol N (1), was isolated from Agrimonia pilosa Ledeb and its structure was determined by (1)H, (13)C NMR and HRESI-MS analyses. Compound 1 inhibited nitric oxide (NO) production in LPS/IFN-γ -induced RAW264.7 macrophages, and then the iNOS gene expression and its protein production with LPS/IFN-γ treatment cells were also suppressed in the presence of 1. In addition, compound 1 scavenged NO or nitrogen radicals generated from NOR3 (4-ethyl-2-hydroxyamino-5-nitro-3-hexenamide) as an NO donor. These results indicated that pilosanol N can decrease the level of NO through a mechanism that involved both a decrease in the NO production and NO scavenging.

Dual biological functions of the apoptotic activity and anti-inflammatory effect by alcyonolide congeners from the Okinawan soft coral, Cespitularia sp.

In our current study, alcyonolide and its congeners isolated from the Okinawan soft coral, Cespitularia sp., have shown an antitumor activity in HCT116 colon cancer cells. This study investigated the biological activities of these compounds (1-12) for the apoptotic activity in the HCT116 cells and the anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. As a result, the apoptotic cells with a nuclear condensation were detected by treatment with these compounds. The apoptotic cells dependent on the caspase 3/7 activation was also induced in the low concentration range of 2.5-10 μM. While a similar concentration of the compounds inhibited the NO production in the LPS-stimulated inflammatory RAW264.7 cells, the pro-inflammatory gene expressions of the iNOS and COX-2 mRNA were also suppressed. The structurally unique alcyonolides (5, 12) having the dual biological activity of apoptotic activity and anti-inflammatory effect could be a potential development as pharmaceutical agents.

Hydrogen peroxide derived from marine peroxy sesquiterpenoids induces apoptosis in HCT116 human colon cancer cells.

In this study, the isolates of the peroxy sesquiterpenoids (1-3) from the Okinawan soft coral, Sinularia sp., indicated cytotoxicity in HCT116 colon cancer cells. The apoptotic cells with a nuclear condensation were detected in the presence of these compounds, then the caspase 3/7 activity was induced, indicating that the compounds have a potential antitumor activity by apoptosis-induction. The cells treated with these compounds were generated reactive oxygen species (ROS), indicating that the ROS is related to the induction of apoptosis. The ROS production reduced in the presence of catalase or trolox, indicating that hydrogen peroxide (H2O2) is generated through a certain free radical reaction derived from the compound. In fact, the accumulation of intracellular H2O2 was also confirmed in the presence of these compounds. Based on all the results, this study proposed the apoptosis-inducing mechanism due to the compounds that the H2O2 produced involving free radical reactions derived from cleavage of the end or hydro-peroxide in the molecule induced cell death.

Endoperoxy and hydroperoxy cadinane-type sesquiterpenoids from an Okinawan soft coral, Sinularia sp.

Three cadinane-type sesquiterpenoids, endoperoxide (1) and hydroperoxides (2, 3) together with three known sesquiterpenoids (4–6) were isolated from an Okinawan soft coral, Sinularia species. Structures of these isolates were elucidated by spectroscopic analyses (NMR, IR and MS) and molecular modeling. In addition, the isolates 1–3 as new compounds were examined for biological activities, resulting that they have antibacterial activity and weak cytotoxicity against HCT116 cells as well as anti-inflammatory effect on LPS/IFN-γ-stimulated RAW 264.7 macrophage cells.