Takahiro Hosoya

Chrotacumines A—D, Chromone Alkaloids from Dysoxylum acutangulum

Four new chromone alkaloids, chrotacumines A-D (1-4), consisting of a 5,7-dihydroxy-2-methylchromone, an N-Me piperidine ring, and an ester side chain were isolated from Dysoxylum acutangulum, and their structures including absolute configurations were elucidated on the basis of spectroscopic data interpretation including 2D NMR, CD spectra, and X-ray analysis. The known compound rohitukine (5) showed moderate cytotoxicity against human HL-60 promyelocytic leukemia and HCT-116 colon cancer cells.

Biscarpamontamines A and B, an aspidosperma-iboga bisindole alkaloid and an aspidosperma-aspidosperma bisindole alkaloid, from Tabernaemontana sphaerocarpa.

Two new bisindole alkaloids, biscarpamontamine A (1), possessing an aspidosperma-iboga-type skeleton, and biscarpamontamine B (2), having an aspidosperma-aspidosperma-type skeleton, were isolated from stems of Tabernaemontana sphaerocarpa, and their structures were elucidated on the basis of spectroscopic data analysis. The absolute configuration of biscarpamontamine B (2) was established by comparison of its CD spectrum and with that of vobtusine (3). Biscarpamontamine B (2) showed potent cytotoxicity against various human cancer cell lines.

Identification of the phenolic compounds contributing to antibacterial activity in ethanol extracts of Brazilian red propolis

The purpose of this study is to identify the quantity and antibacterial activity of the individual phenolic compounds in Brazilian red propolis. Quantitative analysis of the 12 phenolic compounds in Brazilian red propolis was carried out using reversed-phase high-performance liquid chromatography. The main phenolic compounds in Brazilian red propolis were found to be (3S)-vestitol (1), (3S)-neovestitol (2) and (6aS,11aS)-medicarpin (4) with quantities of 72.9, 66.9 and 30.8 mg g of ethanol extracts− 1, respectively. Moreover, the antibacterial activities of each compound against Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa were evaluated by measuring the minimum inhibitory concentrations. In particular, compound 4 exhibited the most potent antibacterial activity among all the assayed compounds against selected bacteria, indicating that 4 is the most active compound in Brazilian red propolis extracts. Thus, Brazilian red propolis may be used as food additives and pharmaceuticals to protect against bacteria.

Solophenols B–D and Solomonin: New Prenylated Polyphenols Isolated from Propolis Collected from The Solomon Islands and Their Antibacterial Activity.

Three new prenylated flavonoids, namely, solophenols B (1), C (2), and D (3), as well as a new prenylated stilbene, solomonin (4), were isolated from propolis collected from the Solomon Islands. In addition, 17 known compounds were identified. The structures of the new compounds were determined by a combination of methods, including mass spectrometry and NMR. These new compounds and several known compounds were tested for antibacterial activity against Staphylococcus aureus, Bacillus subtilis, and Pseudomonas aeruginosa. Most of them exhibited potent antibacterial activity. These findings may indicate that propolis from the Solomon Islands has potential applications as an ingredient in food additives or pharmaceuticals.

Trichostatin analogues JBIR-109, JBIR-110, and JBIR-111 from the marine sponge-derived Streptomyces sp. RM72.

Three new trichostatin analogues, JBIR-109 (1), JBIR-110 (2), and JBIR-111 (3), were isolated from the culture of the marine sponge-derived Streptomyces sp. strain RM72, together with trichostatin A (4) and trichostatic acid (5). The planar structures of 1-3 were determined on the basis of extensive NMR and MS analyses. In addition, the absolute configurations of the amino acid residues were determined by Marfeys method. The histone deacetylase inhibitory activities of 1-5 were examined, and their structure-activity relationships are discussed.

Absorption and Metabolism of Luteolin and Its Glycosides from the Extract of Chrysanthemum morifolium Flowers in Rats and Caco-2 Cells.

To elucidate the bioavailability of luteolin and its glycosides in Chrysanthemum morifolium flowers, the absorption and metabolism of luteolin from them was investigated in rats and Caco-2 cells using HPLC and LC-MS. After oral administration of C. morifolium extract (1.7 g/kg body weight (bw), equivalent to 22.8 and 58.3 μmol/kg bw of luteolin and luteolin-7-O-glucoside, respectively) to rats, luteolin and its glycosides were quickly absorbed and luteolin, luteolin monoglucoside, and luteolin monoglucuronide were detected in the plasma. Their levels were highest at 1 h after administration (0.76 ± 0.27 μM). These compounds were also detected in media on the basolateral side from Caco-2 cells treated with the C. morifolium extract. These results suggest that luteolin and luteolin monoglucoside are rapidly absorbed after administration of C. morifolium flower extract and that luteolin, luteolin monoglucoside, and luteolin monoglucuronide may circulate in humans.

Epigallocatechin Gallate Decreases the Micellar Solubility of Cholesterol via Specific Interaction with Phosphatidylcholine

The mechanisms underlying the effect of epigallocatechin gallate (EGCG) on the micellar solubility of cholesterol were examined. EGCG eliminated both cholesterol and phosphatidylcholine (PC) from bile salt micelles in a dose-dependent manner in vitro. When the bile salt micelles contained a phospholipid other than PC, neither cholesterol nor the phospholipid was eliminated following the addition of EGCG. When vesicles comprised of various phospholipids were prepared and, EGCG was added to the vesicles, EGCG effectively and exclusively eliminated only PC. An intermolecular nuclear Overhauser effect (NOE) was observed between PC and EGCG in bile salt micelles with EGCG added, but not between cholesterol and EGCG, by using a NOE-correlated spectroscopy nuclear magnetic resonance method. The results of binding analyses using surface plasmon resonance (SPR) showed that EGCG did not bind to cholesterol. These observations strongly suggest that EGCG decreases the micellar solubility of cholesterol via specific interaction with PC.

Sucutiniranes C―F, Cassane-Type Diterpenes from Bowdichia nitida

Four new cassane-type diterpenes, sucutiniranes C-F (3-6), have been isolated from seeds of Bowdichia nitida, and their structures were elucidated by using 2D NMR data, chemical correlations, and X-ray analysis. Sucutiniranes E (5) and F (6) were moderately cytotoxic against human blood premyelocytic leukemia (HL-60), breast adenocarcinoma (MCF-7), and colon cancer (HCT-116) cells.

A new cyclizidine analog—JBIR-102—from Saccharopolyspora sp. RL78 isolated from mangrove soil

A new cyclizidine analog—JBIR-102—from Saccharopolyspora sp. RL78 isolated from mangrove soil

Nymphaeol-A Isolated from Okinawan Propolis Suppresses Angiogenesis and Induces Caspase-Dependent Apoptosis via Inactivation of Survival Signals

Propolis, a resinous substance that honeybees collect to protect their beehive from enemies, is reported to have various biological activities. In our screening program to search for antiangiogenic compounds from propolis, the ethanol extracts of Okinawan propolis (EEOP) showed significant antiangiogenic activities in a tube formation assay with human umbilical vein endothelial cells (HUVECs) in vitro at 3.13 μg/mL and chorioallantoic membrane (CAM) assay in vivo at 25 μg/egg. To elucidate the active compounds of EEOP and their mode of action, we isolated some prenylated flavonoids from EEOP and found that nymphaeol-A had the strongest antiangiogenic activity among them. Nymphaeol-A significantly reduced in vivo neovessel formation in the CAM assay at 25 μg/egg. At the molecular level, nymphaeol-A markedly inactivated mitogen-activated protein kinase/ERK kinase 1/2 (MEK1/2) and extracellular signal-regulated kinase 1/2 (ERK1/2), whose molecular activations signal new vessel formation in HUVECs. In addition, nymphaeol-A dose- and time-dependently induced caspase-dependent apoptosis in tube-forming HUVECs. Taken together, nymphaeol-A was shown to inhibit angiogenesis at least in part via inactivation of MEK1/2–ERK1/2 signaling and induction of caspase-dependent apoptosis. Okinawan propolis and its major component, nymphaeol-A, may be useful agents for preventing tumor-induced angiogenesis.