Differential annotation of converted metabolites (DAC-Met): Exploration of Maoto (Ma-huang-tang)-derived metabolites in plasma using high-resolution mass spectrometry.

INTRODUCTION: Traditional herbal medicine (THM) contains a vast number of natural compounds with varying degrees of pharmacological activity. To elucidate the mode of action, comprehensive metabolite profiling in the plasma before and after administration of THM is essential. OBJECTIVE: The aim of this study was to explore and identify/annotate converted metabolites after administration of THM in humans. METHODS: We performed untargeted metabolome analysis of human plasma collected before and after administration of maoto (ma-huang-tang), a traditional Japanese Kampo medicine. Maoto-derived metabolites were then selected and annotated following the DAC-Met strategy, which is an annotation method that uses mass differences of major metabolic reactions among the detected peaks and a differential network analysis. RESULTS: About 80% of maoto-derived components were found to be converted forms. Following DAC-Met, the structures of 15 previously unidentified metabolites were determined, and five of these were later confirmed with authentic standards. Using published literature, we also reconstructed the metabolic pathway of maoto components in humans. A kinetic time-course analysis revealed their diverse kinetic profiles. CONCLUSION: The results demonstrated that time-resolved comprehensive metabolite profiling in plasma using the DAC-Met strategy is highly useful for elucidating the complex nature of THM.

Two new isoflavanones from the roots of Erythrina variegata.

Two new isoflavanones, eryvarins Y (1) and Z (2), together with three known compounds (3-5) were isolated from the roots of Erythrina variegata. The structures of 1 and.2 were established on the basis of spectroscopic data. The new compounds are peculiar isoflavanones, possessing both a 3-methylbut-2-en- 1-yl group and a 2-hydroxy-3-methylbut-3-en-1-yl group. Among the isolates, orientanol E (5) exhibited potent antibacterial activity against methicillin- resistant Staphylococcus aureus (MRSA) strains.

Antibacterial constituents from the roots of Erythrina herbacea against methicillin-resistant Staphylococcus aureus.

Two new compounds, erybacin A (1) and erybacin B (2), together with 10 known compounds (3- 12), were isolated from the roots of Erythrina herbacea. Their structures were established on the basis of spectroscopic analyses. Erybacin A is a rare, naturally occurring 1-hydroxy-1,3-diphenylpropan-2-one derivative. The isolated compounds were evaluated for their antibacterial activity against 13 strains of methicillin-resistant Staphylococcus aureus (MRSA). The new compound 2 showed a potent bactericidal activity against MRSA.

A new biisoflavonoid from the roots of Erythrina variegata.

A new biisoflavonoid, biseryvarin A (1a), together with two known compounds were isolated from the roots of Erythrina variegata. The structure of biseryvarin A was established on the basis of spectroscopic evidence. Biseryvarin A is the first dimeric isoflavonoid possessing isoprenoid groups from the genus Erythrina. Biseryvarin A showed low activity against methicillin-resistant Staphylococcus aureus (MRSA).

A new amide from the leaves and twigs of Litsea auriculata.

A new amide, N-trans-sinapoylmethoxytyramine (1), along with three known amides (2-4) and two known flavonol 3-O-rhamnosides (5 and 6), were isolated from the leaves and twigs of Litsea auriculata. The structures of the isolated compounds (1-6) were characterized on the basis of spectroscopic analyses, and their cytotoxic activity against HeLa cells was estimated.

Synergistic effects of mupirocin and an isoflavanone isolated from Erythrina variegata on growth and recovery of methicillin-resistant Staphylococcus aureus.

The phytochemical 2',4'-dihydroxy-8-gamma,gamma-dimethylallyl-2",2"-dimethylpyrano[5",6":6,7]isoflavanone (bidwillon B) was isolated from Erythrina variegata and its antibacterial properties against methicillin-resistant Staphylococcus aureus (MRSA) were investigated. Bidwillon B inhibited the growth of 12 MRSA strains at minimum inhibitory concentrations (MICs) of 3.13-6.25mg/l, while MICs of mupirocin were 0.20-3.13 mg/l. The minimum bactericidal concentration (MBC) for bidwillon B and mupirocin against MRSA were 6.25-25mg/l (MBC(90): 12.5mg/l) and 3.13-25mg/l (MBC(90): 25mg/l), respectively. When bidwillon B and mupirocin were combined, synergistic effects were observed for 11 strains of MRSA (fractional inhibitory concentration indices, 0.5-0.75). The MBCs of mupirocin in the presence of bidwillon B (3.13 mg/l) were reduced to 0.05-1.56 mg/l. Bidwillon B at MIC values strongly inhibited incorporation of radio-labelled thymidine, uridine, glucose and isoleucine into MRSA cells. Mupirocin showed lower inhibitory effects than bidwillon B on thymidine, uridine and glucose incorporation, but incorporation of isoleucine was completely blocked with this antibiotic. These results indicate that bidwillon B possesses sufficient anti-MRSA activity for inhibiting growth and recovery, and that the compound acts synergistically with mupirocin. The results also suggest that both compounds act on MRSA via different mechanisms. Bidwillon B may prove to be a potent phytotherapeutic and/or combination agent with mupirocin in the elimination of nasal and skin carriage of MRSA.

Six new constituents from the roots of Erythrina variegata.

Three new isoflavonoids, eryvarins M-O (1-3), two new 2-arylbenzofurans, eryvarins P and Q (4 and 5), and a new 3-aryl-2,3-dihydrobenzofuran, eryvarin R (6), together with three known compounds, were isolated from the roots of Erythrina variegata. The structures of these compounds were established by spectroscopic analysis. Eryvarin R (6) is an unusual 3-aryl-2,3-dihydrobenzofuran derivative with a formyl (CHO) group. Eryvarin Q (5) showed potent antibacterial activity against methicillin-resistant Staphylococcus aureus.