Herein, ring-cleaved (24) and truncated (25) analogues of an azasugar, 1-deoxynojirimycin (23), exhibited inhibitory activity (Ki = 4-10 μM) equal to that of the parent compound (1, Ki = 14 μM). Based on this structure-activity relationship (SAR), four ring-cleaved (26a-26c and 27c) and three truncated (28a-28c) analogues of salacinol (1), a potent thiosugar-ring-containing α-glucosidase inhibitor, were synthesised. Bioassay results revealed that all the synthetics were inactive, indicating that the 5-membered thiosugar ring of 1 played an essential role in the potent activities of sulfonium-type inhibitors. The present findings are interesting and important in understanding the function of salacinol, considering that the observed inhibitory activity trend was contrary to the SAR observed in aza-compounds (23, 24, and 25) in a previous study, which suggested that the cyclic structure did not contribute to their strong inhibitory activity.

Fruit from the Prunus mume tree is a traditional food in Japan. Recently, bainiku-ekisu, an infused juice concentrate of Japanese Prunus mume, is attracting attention as a health promoting supplement. Angiotensin II (Ang II) plays a central role in development of hypertension. It has been reported that bainiku-ekisu treatment attenuates the growth-promoting signaling induced by Ang II in vascular smooth muscle cells. However, whether bainiku-ekisu has any effect on an animal model of hypertension remains unknown. Therefore, this study was designed to explore the potential anti-hypertensive benefit of bainiku-ekisu utilizing a mouse model of hypertension with Ang II infusion. Male C57BL/6 mice were infused with Ang II for 2 weeks and given 0.1% bainiku-ekisu containing water or normal water for 2 weeks with blood pressure evaluation. After 2 weeks, mice were euthanized, and the aortas were collected for evaluation of remodeling. Aortic medial hypertrophy was observed in control mice after Ang II infusion, which was attenuated in bainiku-ekisu group with Ang II infusion. Bainiku-ekisu further attenuated aortic induction of collagen producing cells and immune cell infiltration. Development of hypertension induced by Ang II was also prevented by bainiku-ekisu. Echocardiograph indicated protection of Ang II-induced cardiac hypertrophy by bainiku-ekisu. In vascular fibroblasts, bainiku-ekisu attenuated vascular cell adhesion molecule-1 induction, an endoplasmic reticulum stress marker, inositol requiring enzyme-1α phosphorylation, and enhancement in glucose consumption in response to Ang II. In conclusion, Bainiku-ekisu prevented Ang II-induced hypertension and inflammatory vascular remodeling. Potential cardiovascular health benefit to taking bainiku-ekisu should be further studied.

Poly-trans-[ (2-carboxyethyl)germasesquioxane] (Ge-132), an organogermanium, is hydrolyzed to 3-(trihydroxygermyl)propanoic acid (THGP) in aqueous solutions, and reduces inflammation, pain and cancer, whereas the underlying mechanisms remain unknown. Sulfides including H2S, a gasotransmitter, generated from l-cysteine by some enzymes including cystathionine-γ-lyase (CSE), are pro-nociceptive, since they enhance Cav3.2 T-type Ca2+ channel activity expressed in the primary afferents, most probably by canceling the channel inhibition by Zn2+ linked via coordinate bonding to His191 of Cav3.2. Given that germanium is reactive to sulfur, we tested whether THGP would directly trap sulfide, and inhibit sulfide-induced enhancement of Cav3.2 activity and sulfide-dependent pain in mice. Using mass spectrometry and 1H NMR techniques, we demonstrated that THGP directly reacted with sulfides including Na2S and NaSH, and formed a sulfur-containing reaction product, which decreased in the presence of ZnCl2. In Cav3.2-transfected HEK293 cells, THGP inhibited the sulfide-induced enhancement of T-type Ca2+ channel-dependent membrane currents. In mice, THGP, administered systemically or locally, inhibited the mechanical allodynia caused by intraplantar Na2S. In the mice with cyclophosphamide-induced cystitis and cerulein-induced pancreatitis, which exhibited upregulation of CSE in the bladder and pancreas, respectively, systemic administration of THGP as well as a selective T-type Ca2+ channel inhibitor suppressed the cystitis-related and pancreatitis-related visceral pain. These data suggest that THGP traps sulfide and inhibits sulfide-induced enhancement of Cav3.2 activity, leading to suppression of Cav3.2-dependent pain caused by sulfide applied exogenously and generated endogenously.

Although 4,5-didehydroguadiscine (12a), an alkaloid with potent melanogenesis-inhibitory activity isolated from Hornschuchia obliqua (Annonaceae), consists of an aporphine nucleus with an aromatized B-ring, to date, it has not been utilized as a template for structure-activity relationship (SAR) studies of pharmacological activities because of its exceptional structure. Accordingly, herein, five analogs (12b-12f) of 12a and five benzylisoquinoline analogs (13b-13f) lacking the C11a-C11b bond of 12b-12f were prepared. The inhibitory effects of 12b-12f and 13b-13f on melanogenesis in theophylline-stimulated B16 melanoma 4A5 cells were examined and compared with those of 12a. Melanogenesis-inhibitory activities of 12b-12f were the same as that of 12a, whereas the melanogenesis-inhibitory activities of 13b-13f were significantly inferior to those of 12a and 12b-12f. These results suggest that the C11a-C11b bond plays an essential role in the melanogenesis-inhibitory activities of 12a-12e.

The seed oil of Carapa guianensis Aublet (Andiroba) has been used in folk medicine for its insect-repelling, anti-inflammatory, and anti-malarial activities. This study aimed to examine the triglyceride (TG) reducing effects of C. guianensis-derived limonoids or other commercially available limonoids in human hepatoblastoma HepG2 cells and evaluate the expression of lipid metabolism or autophagy-related proteins by treatment with 7-deacetoxy-7-oxogedunin (DAOG; 1), a principal limonoid of C. guianensis. The gedunin-type limonoids, such as DAOG (% of control at 20 μM: 70.9 ± 0.9%), gedunin (2, 74.0 ± 1.1%), epoxyazadiradione (4, 73.4 ± 2.0%), 17β-hydroxyazadiradione (5, 79.9 ± 0.6%), 7-deacetoxy-7α-hydroxygedunin (6, 61.0 ± 1.2%), andirolide H (7, 87.4 ± 2.2%), and 6α-hydroxygedunin (8, 84.5 ± 1.1%), were observed to reduce the TG content at lower concentrations than berberine chloride (BBR, a positive control, 84.1 ± 0.3% at 30 μM) in HepG2 cells pretreated with high glucose and oleic acid. Andirobin-, obacunol-, nimbin-, and salannin-type limonoids showed no effect on the intracellular TG content in HepG2 cells. The TG-reducing effect of DAOG was attenuated by the concomitant use of compound C (dorsomorphin), an AMPK inhibitor. Further investigation on the detailed mechanism of action of DAOG at non-cytotoxic concentrations revealed that the expressions of autophagy-related proteins, LC3 and p62, were upregulated by treatment with DAOG. These findings suggested that gedunin-type limonoids from Andiroba could ameliorate fatty liver, and that the action of DAOG in particular is mediated by autophagy.

Pyroligneous acids (PA) from hardwood, softwood, and bamboo significantly disinfected encephalomyocarditis virus (EMCV). Twenty-five kinds of phenolic derivatives in the PAs were identified and quantified. The total amounts of phenolic compounds in bamboo PA is higher than those in the PAs from softwood and hardwood. Phenol, 2-methoxyphenol, 2-methoxy-4-methylphenol, and 2-methoxy-4-ethylphenol are the most abundant compounds in the PAs examined. The activities of all the phenolic compounds against the encephalomyocarditis virus were assessed. The number of phenolic hydroxyl groups significantly affects the antiviral activity, and catechol and its derivatives exhibit higher viral inhibition effects than other phenolic derivatives. In addition, substituents affect the antiviral activity of the compounds. Phenolic compounds with a methyl group show higher activities than with a methoxyl group (e.g., 2-methylphenol > 2-methoxyphenol). Moreover, the relative position of functional groups also plays a key role in the viral inhibition activity (e.g., 2,6-dimethoxyphenol > 3,4-dimethoxyphenol). Thus, PAs contain phenol derivatives with considerable structural diversity and viral inhibition activities, providing a new strategy for virus-inactivation treatment through the optimization of PA-derived phenol structures.

The compositions of the essential oils from three kinds of Ciyptotaenia japonica Hassk ("Mitsuba" in Japanese, Kirimitsuba (KM), Nemitsuba (NM), and Itomitsuba (IM)) were investigated by capillary GC/GC-MS. The oils contained 53 volatile components, of which 95% were terpenoids. The major constituents were sesquiterpenoids, which were alpha-selinene (KM: 39.1%; NM: 38.4%; IM: 13.2%), beta-selinene (15.5%, 15.2%, 4.8%), germacrene D (12.1%, 7.2%, 24.1%), trans-farnesene (11.1%, 6.0%, 10.9%), beta-elemene (2.9%, 2.9%, 6.8%), and trans-caryophyllene (1.7%, 1.7%, 2.6%). The main sesquiterpene found in KM and NM was alpha-selinene and in IM was germacrene D. The major monoterpenes found were beta-myrcene (3.8%, 6.7%, and 3.5%) and beta-pinene (2.8%, 0.2%, and 1.4%).

Chiroptical signs in circularly polarised luminescence (CPL) of Eu(III) luminophores coordinated to C-2-symmetric binaphthyl ring carrying carboxylic acids, (R)-1 (and (S)-1)) and (R)-2 (and (S)-2)) were inverted by inserting two oxymethylene spacers between the ring and the acids. The subtle difference in reorganization between (R)-1 and (R)-2 causes the apparent CPL sign-swapping characteristics. We assume that (R)-2 is more likely to undergo this reorganization rather than (R)-1 because of the highly flexible spacer and vice versa. The subtle difference in the rotational freedom of the ligands with and without the two spacers causes the opposite CPL signs although (R)-1/Eu and (R)-2/Eu had the same CD sign in the ground state. This was proven by experimental and theoretical data.

Using biotransformation as a biocatalytic process has the advantage of being able to proceed under mild conditions and with high regio- and enantioselectivity. This study investigated the biotransformation of (-)-(1R,4S)-menthone (1) and (+)-(1S,4R)-menthone (2) by Spodoptera litura larvae. Compound 1 was converted to (-)-(1R,4S)-7-hydroxymenthone (1-1), (+)-(1R,35,4S)-7-hydroxyneomenthol (1-2) and (-)-(1R,4S,8R)-p-menth-3-one-9-oic acid (1-3). The metabolism of substrate 2 generated three enantiomers of the above metabolites, designated as 2-1 to 2-3, respectively. The C-9 position of ()-menthone and (+)-menthone was oxidized to carboxylic acid by S. litura, which is a metabolic pathway not observed in any other example of biocatalysis.

Inhibition of beta-secretase (BACE1) is currently regarded as the leading treatment strategy for Alzheimer's disease. In the present study, we aimed to screen the in vitro inhibitory activity of 80 types of aroma compounds (monoterpenes, sesquiterpenes, and C-13 norisoprenoids), including plant-based types, at a 200-mu M concentration against a recombinant human BACEI. The results showed that the most potent inhibitor of BACE1 was geranyl acetone followed by (+)-camphor, (-)-fenchone, (+)-fenchone, and (-)-camphor with the half-maximal inhibitory concentration (IC50) values of 51.9 +/- 3.9, 95.9 +/- 11.0, 106.3 +/- 14.9, 117.0 +/- 18.6, and 134.1 +/- 16.4 mu M, respectively. Furthermore, the mechanism of inhibition of BACE1 by geranyl acetone was analyzed using Dixon kinetics plus Cornish-Bowden plots, which revealed mixed-type mode. Therefore aroma compounds may be used as potential lead molecules for designing anti-BACE1 agents.

The first total syntheses of the geranylated pyranocoumarins, mameasins C (1) and D (2), aromatase inhibitors isolated from the flowers of Mammea siamensis, were accomplished in five steps, starting from phloroglucinol 3. In this strategy, the characteristic pyran ring-fused coumarin core of 1 and 2 was effectively constructed by Friedel-Crafts acylation of 3, followed by Reformatsky reaction of the resultant ketone to give a key coumarin intermediate 9. Compound 9 was converted to targets 1 and 2 in a stepwise manner by successive C-acylation and O-geranylation, followed by a [1,3]-sigmatropic geranyl shift. Furthermore, screening of intermediates obtained in the synthetic pathway to 1 and 2 revealed that de-geranylated pyranocoumarins (10 and 11) show superior aromatase inhibitory activity as compared to the natural products 1 and 2. (C) 2017 Elsevier Ltd. All rights reserved.

The metabolism of the norisoprenoid beta-ionone was investigated in vitro using human liver microsomes and 11 different recombinant cytochrome P450 enzymes expressed in Trichoplusia ni cells. beta-Ionone was found to be oxidized via 4S-hydroxylation by CYP2B6 in human liver microsomes. CYP1A2 also regioselectively catalyzed the hydroxylation of beta-ionone to yield 4-hydroxylation; this conversion was not stereoselective. Further kinetic analysis revealed that CYP2B6 exhibited the highest activity for beta-ionone 4-hydroxylation. Kinetic analysis showed that K-m and V-max for oxidation of beta-ionone by CYP1A2 and CYP2B6 was 107.9 +/- 36.0 mu M and 3200.3 +/- 323.0 nmol/min/nmol P450 and 5.6 +/- 1.2 mu M and 572.8 +/- 29.8 nmol/min/nmol P450, respectively. The reaction rates observed using human liver microsomes and recombinant CYP2B6 were very high compared with those of other CYP2B6 substrates reported thus far. These results suggest that beta-ionone, a norisoprenoid present in nature, is one of the effective substrates for CYP2B enzymes in human liver microsomes. To the best of our knowledge, this is the first time that 4-hydroxy beta-ionone has been described as a human metabolite of beta-ionone.

A facile and highly diastereoselective route to potent natural a-glucosidase inhibitors, i.e., neosalacinol (4) and neoponkoranol (6), isolated from the traditional Ayurvedic medicine "Salacia" was developed by intramolecular cyclization of appropriately substituted sulfides (9 and 12).

Two sample preparation methods, namely hydrodistillation (HD) and solvent-assisted flavor evaporation (SAFE), have been used to investigate the essential oils of the aerial parts (leaves and stems) of Symplocarpus foetidus, a plant with a characteristic odor, by gas chromatography mass spectrometry (GC-MS). Characteristic aroma-active compounds in the oils were detected by GC-Olfactometry (GC-O) and aroma extract dilution analysis (AEDA). From the HD method, the main compounds in the oil were found to be p-vinyl-guaiacol (15.5%), 2-pentyl-furan (13.4%), and (2)-ligustilide (9.5%). From the SAFE method, the main compounds were 2-butoxy-ethanol (49.6%), ethyl-pentanoate (4.5%), and mesitylene (4.0%). In HD oil, the most intense aroma-active compounds were 2-pentyl-furan (flavor dilution factor (FD) = 32, odor activity value (OAV) = 57), p-vinyl-guaiacol (FD = 16, OAV = 41), and dimethyl disulfide (FD = 16, OAV = 41). In SAFE oil, the main aroma-active compounds were 2-butoxy ethanol (FD = 32, OAV = 16), and 2-methoxy thiazole (FD = 32, OAV = 25).

The aim of this study was to investigate the chemical composition and the odor-active components of volatile oils from three edible mushrooms, Pleurotus ostreatus, Pleurotus eryngii, and Pleurotus abalonus, which are well-known edible mushrooms. The volatile components in these oils were extracted by hydrodistillation and identified by GC/MS, GC-olfactometry (GC-O), and aroma extract dilution analysis (AEDA). The oils contained 40, 20, and 53 components, representing 83.4, 86.0, and 90.8% of the total oils in P. ostreatus, P. eryngii, and P. abalonus, respectively. Odor evaluation of the volatile oils from the three edible mushrooms was also carried out using GC-O, AEDA, and odor activity values, by which 13, eight, and ten aroma-active components were identified in P. ostreatus, P. eryngii, and P. abalonus, respectively. The most aroma-active compounds were C-8-aliphatic compounds (oct-1-en-3-ol, octan-3-one, and octanal) and/or C-9-aliphatic aldehydes (nonanal and (2E)-non-2-enal).

The chemical composition of essential oil extracted from Uncaria Hook ("Chotoko" in Japanese), the branch with curved hook of the herbal medicine Uncaria rhynchophylla has been investigated by GC and GC-MS analyses. Eighty-four compounds, representing 90.8% of the total content was identified in oil obtained from Uncaria Hook. The main components i were (E)-cinnamaldehyde (13.4%), alpha-copaene (8.0%), methyl eugenol (6.8%), delta-cadinene (5.3%), and curcumene (3.6%). The important key aroma-active compounds in the oil were detected by gas chromatography-olfactometry (GC-O) and aroma extract dilution analysis (AEDA), using the flavor dilution (FD) factor to express the odor potency of each compounds. Furthermore, the odor activity value (OAV) has been used as a measure of the relative contribution of each compound to the aroma of the Uncaria Hook oil. The GC-O and AEDA results showed that alpha-copaene (FD = 4, OAV = 4376), (E)-linalool oxide (FD = 64, OAV = 9.1), and methyl eugenol (FD = 64, OAV = 29) contributed to the woody and spicy odor of Uncaria Hook oil, whereas furfural (FD = 8, OAV = 4808) contributed to its sweet odor. These results warrant further investigations of the application of essential oil from Uncaria Hook in the phytochemical and medicinal fields.

The chemical compositions of essential oils from the flower and aerial parts (i.e., leaf and branch) of Eurya japonica were determined and quantified using gas chromatography-mass spectrometry (GC-MS). A total of 87 and 50 compounds were detected in the oils from the flower and aerial parts, respectively. The main compounds of the flower oil were linalool (14.0%), (9Z)-tricosene (12.0%), and nonanal (7.4%). In the oil from the aerial parts, linalool (37.7%), alpha-terpineol (13.5%), and geraniol (9.6%) were detected. In the oils from the flower and aerial parts, 13 and 8 aroma-active compounds were identified by GC-olfactometry (GC-O) analysis, respectively. The key aroma-active compounds of the flower oil were heptanal 1 fatty, green, flavor dilution (FD) = 128, odor activity value (OAV) = 3461, nonanal (sweet, citrus, FD = 128, OAV = 491), and eugenol (sweet, spicy, FD = 64, OAV = 62): in the oil from the aerial parts, the key aroma-active compounds were linalool (sweet, citrus, FD = 64, OAV = 95), (E)-beta-damascenone (sweet, FD = 256, OAV = 4000), and (E)-beta-ionone (floral, violet, FD = 128, OAV = 120). This study revealed that nonanal and eugenol impart the sweet, citrus, and spicy odor of the flower oil, while (E)-beta-damascenone and (E)-beta-ionone contribute the floral and sweet odor of the oil from the aerial parts.

In this study, we investigated the use of insects as biocatalysts for the biotransformation of monoterpenoids such as (+)-(1R,2S,4R)-bomeol (1) and (-)-(1S,2R,4S)-borneol (2) by the larvae of Spodoptera litura. The substrates were administrated to the fourth instar larvae of S. litura through food, and the metabolites were collected in the feces. Analysis showed that substrate 1 was converted into the following 12 metabolites: (+)-(1R,2S,4R)-bomeol linoleate (1-1), (+)-(1R,2S,4R)-bomeol linolenate (1-2), (+)-(1R,25,4R)-bomeol-2-O-beta-D-glucopyranoside (1-3), (+)-(1R,2S,4R,5S)-5-endo-hydroxyborneol (1-4), (+)-(1R,4R,5S)-5-endo-hydroxycamphor (1-5), (+)-(1R,2S,4R,5R)-5-exo-hydroxybomeol (1-6), (+)-(1R,4R,5R)-5-exo-hydroxycamphor (1-7), (+)-(1R,2S,4R,7R)-8-hydroxybomeol (1-8), (+)-(1R,4R,7R)-8-hydroxy camphor (1-9), (+)-(1R,2S,4R,7S)-9-hydroxyborneol (1-10), (+)-(1R,2S,4R)-10-hydroxyborneol (1-11), and (+)-(1R,2R,3S,4S)-3-endo-hydroxybomeol (1-12). The metabolism of substrate 2 generated 12 enantiomers of the above metabolites, namely 2-1 to 2-12. Compounds 1-1,1-2,1-3,2-1,2-2,2-8, 2-10, and 2-12 are novel compounds. The main metabolites were generated by phase II reactions such as esterification or glucosidation of the parent substrates. The minor metabolites originated from phase I reactions such as hydroxylation or oxidation, probably by cytochrome P450 enzymes. These fatty acid and glucose conjugation reactions are new metabolic pathways, compared with those reported in previous studies on monoterpenoids in S. litura. (C) 2015 Elsevier B.V. All rights reserved.

IntroductionThe Chrysanthemum genus consisting of about 200 species is mainly distributed over the Northern Hemisphere. Despite the pleasant odour of C. japonense var. debile (setonojigiku), no detailed analysis of the aroma-active compounds has been reported using sensory evaluation. ObjectivesUsing a hydrodistillation (HD) and a solvent-assisted flavour evaporation (SAFE) method to obtain the volatile oil from the leaf parts. MethodsTo clarify odorants contributing to the characteristic aroma-active compounds, the aroma-extract dilution analysis (AEDA) method was performed through gas chromatography olfactometry (GC/O) analysis. In addition, the odour activity value (OAV) was calculated in order to determine the relative contribution of each compound to the aroma-active compounds. ResultsA total of 42 components by HD oil were identified by GC-MS, whereas 34 components were identified in SAFE oil. Thirteen compounds were identified by GC/O analysis in HD and SAFE oils respectively. ConclusionEach extraction method has its own advantages and disadvantages, and they are generally complementary to each other. On the basis of AEDA, OAV and sensory evaluations, [2.2.1] bicyclic monoterpenes (borneol, bornyl acetate and camphor) and -caryophyllene are considered to be the main aroma-active compounds of both extraction methods. Copyright (c) 2014 John Wiley & Sons, Ltd. The Chrysanthemum genus consisting of about 200 species is mainly distributed over the Northern Hemisphere. Despite the pleasant odour of C. japonense var. debile (setonojigiku), no detailed analysis of the aroma-active compounds has been reported using sensory evaluation. Using a hydrodistillation (HD) and a solvent-assisted flavour evaporation (SAFE) method to obtain the volatile oil from the leaf parts. On the basis of AEDA, OAV and sensory evaluations, borneol is considered to be the main aroma-active compounds of both extraction methods.

The chemical composition of volatile oil from agitake (Pleurotus eryngii var. ferulae) was established for the first time using gas chromatography (GC) and GC-mass spectrometry. Sixty-seven and 24 components were extracted by hydrodistillation (HD) using diethyl ether (DE) and dichloromethane (DM), respectively; these components accounted for 80.3% and 91.8% of the total oil, respectively. Thirteen and 48 components of were extracted by the solvent-assisted flavor evaporation method (SAFE), using DE and DM, respectively, and identified; these components accounted for 83.5% and 82.0% of the total oil, respectively. Methylsuccinimide and 2,3,7-trimethyl-2-octene were the most characteristic components by SAFE using DM. Odor evaluation of the volatile oil from agitake was also carried out using GC-olfactometry (GC-O), aroma extraction dilution analysis (AEDA), and the odor activity value (OAV). Sixteen, 8, 5 and 9 aroma-active components were identified using HD (DE and DM) and SAFE (DE and DM), respectively. The main aroma-active components extracted using HD and SAFE were 1-octen-3-ol (mushroom-like) and phenylacetaldehyde (floral), respectively. This study proved that HD and SAFE can be used as complementary extraction techniques for the complete characterization of volatile oil from agitake.

In this study, the aroma-active compounds in the dried flower of Malva sylvestris L. were extracted by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS), and gas chromatography-olfactometry (GC-O) and aroma extraction dilution analysis (AEDA). A light yellow oil with a sweet odor was obtained with a percentage yield of 0.039% (w/w), and 143 volatile compounds (89.86%) were identified by GC-MS. The main compounds were hexadecanoic acid (10.1%), pentacosane (4.8%) and 6,10,14-trimethyl-2-pentadecanone (4.1%). The essential oil consisted mainly of hydrocarbons (25.40%) followed by, alcohols (18.78%), acids (16.66%), ethers (5.01%) ketones (7.28%), esters(12.43%), aldehydes (2.30%) and others (2.00%). Of these compounds, 20 were determined by GC-O and AEDA, to be odor-active (FD (favor dilution) factor ≥ 1). (3-Damascenone (FD = 9, sweet), phenylacetaldehyde (FD = 8, foral, honey-like) and (E)-p-ocimene (FD = 8, spicy) were the most intense aroma-active compounds in M. sylvestris. In order to determine the relative contribution of each of the compounds to the aroma of M. sylvestris, odor activity values (OAVs) were used. p-Damascenone had the highest odor activity values (OAV) (50700), followed by (E)-p-ionone (15444) and decanal (3510). In particular, p-damascenone had a high FD factors, and therefore, this compound was considered to be the main aroma-active components of the essential oil. On the basis of AEDA, OAVs, and sensory evaluation results, p-damascenone is estimated to be the main aroma-active compound of the essential oil. © 2013 by Japan Oil Chemists' Society.

The aim of the present study was to investigate the essential oils isolated from fower and leaf in order to get insight into similarities and differences as to their aroma-active composition. The essential oil obtained from the two parts were analyzed by gas chromatography-mass spectrometry and gas chromatography olfactometry (GC-O). Flower and leaf oils, 38 and 36 constituents, representing 96.4 and 91.0% of the total oil composition, respectively, were identified. The main compounds in flower oil were camphor (47.64%), bornyl acetate (11.87%), and nojigiku alcohol (6.29%), whereas those in leaf oil were camphor (39.14%), nojigiku alcohol (10.76%) and y-muurolene (7.02%). 13 Aroma-active compounds were identifed by GC-O analysis in fower oil and 12 in leaf oil. The main aroma-active compounds in fower oil were camphor (camphor, FD (flavor dilution) = 7, OAV (odor active value) = 136913), bornyl acetate (camphor, FD = 6, OAV = 113711), and p-caryophyllene (spicy, FD = 5, OAV = 116480). In leaf oil, the main aroma-active compounds were camphor (camphor, FD = 7, OAV = 106784), nojigiku alcohol (camphor, FD = 5, OAV = not determined), and p-caryophyllene (spicy, FD = 6, OAV = 526267). © 2013 by Japan Oil Chemists' Society.

Biotransformation of nerol by larvae of the common cutworm (Spodoptera litura) was investigated. The resulting major metabolites were (2Z,6E)-1-hydroxy-3,7-dimethyl-2,6-octadien-8-oic acid and 8-hydroxynerol, and the minor metabolites were 9-hydroxynerol and (2Z,6E)-1-hydroxy-3,7-dimethyl-2,6-octadien-8-al. (2Z,6E)-1-Hydroxy-3,7-dimethyl-2,6-octadien-8-oic acid is a novel compound. The results indicate that biotransformation of nerol by S. Mora larvae involved 2 pathways; the main pathway involved oxidation at the methyl group of the geminal dimethyl at C-8 position followed by carboxylation, and the minor pathway involved oxidation at the methyl group of the geminal dimethyl at C-9 position.

The essential oils from aerial parts of Scutellaria laeteviolacea was analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The characteristic odor components were also detected in the oil using gas chromatography-olfactometry (GC-O) analysis and aroma extraction dilution analysis (AEDA). As a result, 100 components (accounting for 99.11 %) of S. laeteviolacea, were identified. The major components of S. laeteviolacea oil were found to be 1-octen-3-ol (27.72 %), germacrene D (21.67 %),and β-caryophyllene (9.18 %). The GC-O and AEDA results showed that 1-octen-3-ol, germacrene D, germacrene B, and β-caryophyllene were the most characteristic odor components of the oil. These compounds are thought to contribute to the unique flavor of this plant. © 2013 by Japan Oil Chemists' Society.

The germicidal activity of pyroligneous acid (PA) against a picornavirus, encephalomyocarditis virus (EMCV), was analyzed, and the component responsible for its disinfectant activity was identified. Bamboo PA (BPA) inactivated EMCV, but neutralization of BPA abolished this activity. Using liquid-liquid phase extraction and silica gel column chromatography, the hydrophobic active fraction of BPA was separated and its 12 major components were identified. The active fraction was reconstructed by mixing synthetic chemicals at the determined concentrations, and a subtraction series of one chemical from the complete mixture was prepared. An in vitro virus assay demonstrated that phenol was the sole germicidal component, and acetic acid augmented the phenol's inactivating activity resulting in >5-log decrease in EMCV infectivity. Considering the low environmental risk of PA, these findings suggest that BPA is a potentially useful agent for preventing viral epidemics in agricultural and human environments.

The present study was demonstrated to evaluate the effects of naturally occurring coumarins (NOCs) including simple coumarins, furanocoumarins, and pyranocoumarins on the inhibition of p-secretase (BACE1) activity. Of 41 NOCs examined, some furanocoumarins inhibited BACE1 activity, but simple coumarins and pyranocoumarins did not affect. The most potent inhibitor was 5-geranyloxy-8-methoxypsoralen (31). which has an IC(50) value of 9.9 mu M. Other furanocoumarin derivatives, for example, 8-geranyloxy-5-methoxypsoralen (35), 8-geranyloxypsoralen (24), and bergamottin (18) inhibited BACE1 activity, with the IC50 values <25.0 mu M. Analyses of the inhibition mechanism by Dixon plots and Cornish-Bowden plots showed that compounds 18,31 and 35 were mixed-type inhibitor. The kinetics of inhibition of BACE1 by coumarins 24 was non-competitive inhibitors. (C) 2012 Published by Elsevier Ltd.

Microbial transformation studies conducted on isopimpinellin (1) by the fungus Glomerella cingulata have revealed that 1 was metabolized to give the corresponding reduced acid, 5,8-dimethoxy-6,7-furano-hydrocoumaric acid (2). The structure of metabolite 2 was elucidated by high-resolution mass spectrometry (HR-MS), extensive NMR techniques, including H-1 NMR, C-13 NMR, H-1-H-1 correlation spectroscopy (COSY), heteronuclear multiple quantum coherence (HMQC) and heteonuclear multiple bond coherence (HMBC). The biotransformed product 2 showed weak a in vitro beta-secretase (BACE1) inhibitory effect.

This study was designed to investigate the antigenotoxic effects of a series of naturally occurring furanocoumarins (NOFs) including isoimperatorin, imperatorin, (+)-oxypeucedanin, (+)-byakangelicol, and (+)-byakangelicine on antigenotoxic activities against genotoxicity induced by carcinogens [furylfuramide and N-methyl-N'-nitro-N-nitrosoguanidine], and procarcinogens 2-[2-(acetylamino)-4-amino-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-4) and 2-amino-3,4-dimethyl-3H-imidazo-[4,5-f] quinoline (MeIQ)] to genotoxic metabolites catalyzed by rat S9 or rat and human recombinant cytochrome P450 (CYP) 1As by using the umu test based on SOS response. Five different NOFs, which were found in the human diets, strongly inhibited the umuC induction by procarcinogens, but did not be affected by carcinogens. Notably, isoimperatorin and (+)-byakangelicol were found to be potent inhibitors on the metabolic activation of PBTA-4 and MeIQ to genotoxic metabolites catalyzed by rat and human CYP1A1, or rat and human CYP1A2, respectively. In addition, to elucidate the mechanism of their antigenotoxic effects against procarcinogens, the effects of NOFs on rat and human CYP1A1- or rat and human CYP1A2-related enzyme activities of 7-ethoxyresorufin-O-deethylase (EROD) were also investigated. Reduction of the EROD activities by some of the NOFs with IC50 values of 0.23-20.64 mu M was found to be due to strong inhibition of CYP1A1 and CYP1A2 dependent monooxygenases. Furthermore, the mechanism of inhibitions by NOFs on human CYP1A1 and CYP1A2 was analyzed by means of Dixon plots plus Cornish-Bowden plots. The kinetic studies of inhibition types revealed that these compounds inhibited the human CYP1A1 and CYP1A2 a variety of modes rather than by a uniform one. Moreover, experiments with a two-stage incubation indicated that NOFs, except for imperatorin, inhibited human CYP1A1 in a mechanism-based manner, but directly inhibited human CYP1A2. This data suggest that certain NOFs, to which humans are exposed in the diet, may be capable of affecting the metabolic activation of procarcinogens due to inhibitions of CYP1A1 and CYP1A2 enzymes. Environ. Mol. Mutagen. 52:646-657, 2011. (C) 2011 Wiley Periodicals, Inc.

The in vitro metabolism of (+)-(1S,3S,4R) and (-)-(1R,3R,4S)-menthol enantiomers was examined by incubation with human liver microsomes, and the oxidative metabolites thus formed were analyzed using gas chromatography-mass spectrometry (CC-MS). The (+)- and (-)-menthols were found to be oxidized to the respective (+)-(1S,3S,4S)- and (-)-(1R,3R,4R)-trans-p-menthane-3,8-diol derivatives by human liver microsomal P450 enzymes. Cytochrome P450 (CYP) 2A6 was determined to be the major enzyme involved in the hydroxylation of (+)- and (-)-menthols by human liver microsomes on the basis of the following lines of evidence. First, of 11 recombinant human P450 enzymes tested, CYP2A6 catalyzed the oxidation of (+)- and (-)-menthols. Second, oxidation of (+)- and (-)-menthols was inhibited by (+)-menthofuran and anti-CYP2A6 antibody. Finally, (+)- and (-)-menthol activities were found to correlate with contents of CYP2A6 in liver microsomes of 9 human samples.

Microbial transformation of coumarin, psoralen, and xanthyletin was performed with the fungus Glomerella cingulata. The main reaction pathways involved reduction at alpha,beta-unsaturated delta-lactone ring on coumarin analogue. Coumarin was metabolized by G. cingulata to give the corresponding reduced acid, hydrocoumaric acid. In the biotransformation of psoralen, two reduced metabolites, 6,7-furano-hydrocoumaric acid, and 6,7-furano-o-hydrocoumaryl alcohol were isolated from the incubation of psoralen. Xanthyletin was converted to reduced products 9,9-dimethyl-6,7-pyrano-hydrocoumaric acid and 9,9-dimethyl-6,7-pyrano-o-hydrocoumaryl alcohol by G. cingulata. The structures of the new compounds were characterized using spectroscopic techniques. In addition, all of compounds including methyl ester derivatives of the metabolites were tested for the beta-secretase (BACE1) inhibitory activity in vitro. 6,7-Furano-hydrocoumaric acid methyl ester was shown to possess BACE1 inhibitory activity, and an IC(50) value was 0.84 +/- 0.06 mM. (C) 2010 Published by Elsevier Ltd.

The essential oil, obtained by steam distillation of flowers, leaves and stems from Wisteria brachybotrys Sieb. et Zucc, collected in Japan was analyzed by gas chromatography (GC) and GC-MS. The important aroma-active compounds were also detected in the oil using GC-MS/Olfactometry (GC-MS/O) and aroma extraction dilution analysis (AEDA). As a result, sixty-eight compounds from flowers of W. brachybotrys, accounting for 96.3%, were identified, and benzyl cyanide (31.7%), palmitic acid (8.7%), and (Z)-gamma-bisabolene (8.4%) as the main compounds. Thirty compounds from leaves, accounting for 97.3%, were identified, and phytol (46.0%), palmitic acid (8.2%), and nonanal (5.7%) as the main compounds. Twenty-eight compounds from stems, accounting for 98.7%, were identified, and geraniol (32.8%), linalool (22.1%), and nerol (10.4%) as the main compounds. A preliminary analysis by GC-MS and using Kovats' retention indexes, lead to characterize and quantify the oil constituents, while GC-MS/O was then applied for the identification of the main odorants. By the incremental dilution method (AEDA), applied to the GC-MS/O technique, the flavor dilution (FD) factor was obtained. To our knowledge, the composition of these parts of essential oils is described here for the first time, both from the chemical and olfactometric viewpoints.

Biotransformation studies conducted on (+)-(S)-ar-turmerone (1) and (+)-(S)-dihydro-ar-turmerone (2) by the fungus Aspergillus niger have revealed that 1 was metabolized to give four oxidized metabolites, (+)-(7S)-hydroxydehydroar-todomatuic acid (3), (+)-(7S, 10E)-12-hydroxydehydro-ar-todomatuic acid (4), (+)-(7S,10E)-7,12-dihydroxydehydroar-todomatuic acid (5), and (+)-(7S)-15-carboxy-9,13-epoxy-7-hydroxy-9,13-dehydro-ar-curcumene (6), and (+)-(S)-dihydro-ar-turmerone (2) was metabolized to (+)-7,11-dihydroxy-ar-todomatuic acid (7). Metabolites 3-7 were characterized using spectroscopic techniques. Metabolites 3-7 inhibited acetylcholinesterase (AChE) although less so than the parent substrates.

The biotransformation of bergapten (1) by the fungus Glomerella cingulata gave the corresponding reduced acid, 6,7-furano-5-methoxy hydrocoumaric acid (2), a new compound. Xanthotoxin (3) was also converted to the corresponding reduced acid cnidiol b (4) and demethylated metabolite xanthotoxol (5) by G. cingulata. The structure of the new compound 2 was elucidated by high-resolution mass spectrometry, extensive NMR techniques, including (1)H NMR and (13)C NMR, (1)H-(1)H correlation spectroscopy, heteronuclear multiple quantum coherence, and heteonuclear multiple bond coherence. The methyl ester or methyl ether or methyl ester and ether derivatives of 2 and 4 were synthesized. All compounds were tested for the beta-secretase (BACE1) inhibitory activity in vitro. The methyl ester and ether derivative 8 was shown to possess BACE1 inhibitory activity, and a IC(50) value was 0.64 +/- 0.04 mM.

In the course of screening antidementia agents from natural products, five beta-secretase (BACE1) inhibitors were isolated from the root extract of Angelica dahurica (Umbelliferae). They were identified as furanocoumarins, isoimperatorin (1), imperatorin (2), (+)-oxypeucedanin (3), (+)-byakangelicol (4) and (+)-byakangelicin (5). Among them, compounds 2 and 4 showed significant inhibitory activity against beta-secretase (BACE1) with IC(50) values of 91.8 +/- 7.5 and 104.9 +/- 2.4 mu M, respectively. Compounds 1-5 inhibited BACE1 activity in a dose-dependent manner. Copyright (C) 2009 John Wiley & Sons, Ltd.

Biotransformation studies conducted on the furanocoumarins isoimperatorin (1) and imperatorin (3) have revealed that 1 was metabolized by Glomerella cingulata to give the corresponding reduced acid, 6,7-furano-5-prenyloxy hydrocoumaric acid (2), and 3 was transformed by G. cingulata to give the dealkylated metabolite, xanthotoxol (4) in high yields (83% and 81%), respectively. The structures of the new compound 2 have been established on the basis of spectral data. The metabolites 2 and 4 were tested for the beta-secretase (BACE1) inhibitory activity in vitro, and metabolite 2 slightly inhibited the beta-secretase activity with an IC(50) value of 185.6 +/- 6.8 mu M. The metabolite 4 was less potent activity than compounds 1-3. In addition, methyl ester (2Me), methyl ether (2a) and methyl ester and ether (2aMe) of 2 were synthesized, and investigated for the ability to inhibit beta-secretase. Compound 2aMe exhibited the best beta-secretase inhibitory activity at the IC(50) value 16.2 +/- 1.2 mu M and found to be the 2aMe showed competitive mode of inhibition against beta-secretase with K(i) value 11.3 +/- 2.8 mu M. (C) 2009 Elsevier Ltd. All rights reserved.

Terpenoids, which have many biological activities and have occurred widely in nature, can be artificially synthesized. However, regioselective oxidation of terpenoids is difficult by chemical methods. In this study, (+)- and (-)-citronellene were biotransformed with Spodoptera litura to define the mechanism of metabolism of citronellene and gain a new natural terpenoid. (+)-Citronellene was converted to (2S,3S)-3,7-dimethyl-6-octene-1,2-diol and (2R,3S)-3,7-dimethyl-6octene-1,2-diol (89.7%), (3S,6S)-(-)-3,7-dimethyl-1-octene-6,7-diol (3.8%), (3S)-(6E)-(+)-3,7-dimethyl-1,6-octadien-8-ol (4.2%), and (3S)-(6E)-(+)-3,7-dimethyl-1,6-octadien-8-oic acid (2.3%). In contrast, (-)-citronellene was converted to (2R,3R)-3,7-dimethyl-6-octene-1,2-diol and (2S,3R)-3,7dimethyl-6-octene-1,2-diol (56.3%), (+)-iridan-7,8-diol (3.5%), and (3R)-(6E)-(-)-3,7-dimethyl-1,6-octadien-8-oic acid (40.2%). The main metabolic pathway of (+)- and (-)-citronellene by larvae of S. litura was oxidized at the terminal double bond and trans-allylic methyl position. Particularly on (+)citronellene, the regioselective reaction was shown. On the oxidation of C-6, C-7, and C-8 positions, four new compounds (3S,6S)-(-)-3,7-dimethyl-1-octene-6,7-diol, (3S)-(6E)-(+)-3,7-dimethyl-1,6-octadien-8-oic acid, (+)-iridan-7,8-diol, and (3R)-(6E)-(-)-3,7-dimethyl-1,6-octadien-8-oic acid were produced in regioselective oxidation. It noted that stereoselective oxidation occurred between the enantiomers. The C-6 position was oxidized on the (+)-(3S) form, whereas cyclized and the C-7 position were oxidized on the (-)-(3R) form.