New triterpenoid saponins from <Emphasis Type="Italic">Argania spinosa</Emphasis>

Five new triterpene saponins, arganine L (1), O (2), P (3), Q (4) and R (5), were isolated from the barks of Argania spinosa (L.) Skeels. Arganines L-P and R are bidesmosidic saponins. The structures of 1–5 were elucidated as 3-O-[β-d-xylopyranosyl-(1–4)-β-d-glucuronopyranosyl]-28-O-[β-d-apiofuranosyl-(1–3)-β-d-xylopyranosyl-(1–4)-α-l-rhamnopyranosyl-(1–2)-α-l-arabinopyranosyl] bayogenin, 3-O-[β-d-xylopyranosyl-(1–4)-β-d-glucuronopyranosyl]-28-O-[β-d-xylopyranosyl-(1–4)-α-l-arabinopyranosyl] bayogenin, 3-O-[β-d-xylopyranosyl-(1–4)-β-d-glucuronopyranosyl]-28-O-[α-l-arabinopyranosyl] bayogenin, 3-O-[β-d-xylopyranosyl-(1–4)-β-d-glucuronopyranosyl] bayogenin, and 3-O-[β-d-apiofuranosyl-(1–4)-β-d-glucuronopyranosyl]-28-O-[β-d-xylopyranosyl-(1–4)-α-l-rhamnopyranosyl-(1–2)-α-l-arabinopyranosyl] bayogenin, respectively, mainly on the basis of their spectroscopic data.     

(<Emphasis Type="Italic">Z</Emphasis>)-3-Hexenyl diglycosides from <Emphasis Type="Italic">Spermacoce laevis</Emphasis> Roxb.

A new (Z)-3-hexenyl O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside was isolated from the aerial part of Spermacoce laevis, along with 17 known compounds: (6S,9R)-roseoside, (Z)-3-hexenyl O-β-d-glucopyranoside, (Z)-3-hexenyl O-α-l-rhamnopyranosyl-(1→6)-β-d-glucopyranoside, (Z)-3-hexenyl O-α-l-arabinopyranosyl-(1→6)-β-d-glucopyranoside, phenyethyl O-β-d-glucopyranoside, phenyethyl O-α-l-arabinopyranosyl-(1→6)-β-d-glucopyranoside, phenyethyl O-α-l-rhamnopyranosyl-(1→6)-β-d-glucopyranoside, benzyl O-α-l-arabinopyranosyl-(1→6)-β-d-glucopyranoside, benzyl O-β-d-xylopyranosyl-(1→6)-β-d-glucopyranoside, asperuloside, 6α-hydroxyadoxoside, asperulosidic acid, kaempferol 3-O-β-d-glucopyranoside, kaempferol 3-O-rutinoside, quercetin 3-O-β-d-galactopyranoside, quercetin 3-O-α-l-rhamnopyranosyl-(1→6)-β-d-galactopyranoside, and rutin. The structure determinations were based on physical data and spectroscopic evidence.     

Antileishmanial amides and lignans from <Emphasis Type="Italic">Piper cubeba</Emphasis> and <Emphasis Type="Italic">Piper retrofractum</Emphasis>

The n-hexane, ethyl acetate, methanol, and acetone extracts of Piper cubeba Linn. and P. retrofractum Vahl. (Piperaceae) were evaluated in vitro against promastigotes of Leishmania donovani, and all exhibited significant in vitro activity at 100 μg/ml. Two lignans, cubebin and hinokinin, were isolated from the hexane extract of P. cubeba; and one bis-epoxy lignan, (−)-sesamin, and two amides, pellitorine and piplartine, were isolated from the hexane and methanol extracts of P. retrofractum. Cubebin and piplartine showed significant antileishmanial activity in vitro at 100 μM and were further tested in vivo in a hamster model of visceral leishmaniasis. Piplartine showed activity at 30 mg/kg dose. This is the first report of antileishmanial activity of these two plants and their isolated constituents. NIPER Communication No. 395.     

Secoiridoid glycosides from the leaves of <Emphasis Type="Italic">Hydrangea macrophylla</Emphasis> subsp. <Emphasis Type="Italic">serrata</Emphasis>

Seven secoiridoid glycosides, secologanin dimethyl acetal (1), n-butyl vogeloside (2), n-butyl epi-vogeloside (3), (7R)-n-butyl morroniside (4), hydrangenoside A (5), hydrangenoside C (6), and hydrangenoside A dimethyl acetal (7), have been isolated from the leaves of Hydrangea macrophylla subsp. serrata (Thunb.) Makino (Saxifragaceae). The structures were elucidated on the basis of spectral data.     

Tropane alkaloids from <Emphasis Type="Italic">Erythroxylum emarginatum</Emphasis>

A tropane alkaloid, anhydroecgonine methyl ester N-oxide (2), was isolated for the first time as a naturally occurring compound, with anhydroecgonine methyl ester (1) from the bark of Erythroxylum emarginatum. Compound 1 was also isolated from the twigs. Their structures were elucidated mainly by spectroscopic methods.     

Two novel A-<Emphasis Type="Italic">seco</Emphasis>-rearranged lanostane triterpenoids from <Emphasis Type="Italic">Abies sachalinensis</Emphasis>

Further chemical study led to two new A-seco-rearranged lanostane triterpenoid derivatives (1–2) and one known compound Abiesanolide C (3) from the ethyl acetate (EtOAc) soluble fraction of the MeOH extract of Abies sachalinensis needles. The new compounds were identified as 3,4-seco-8-(14→13R)abeo-17,13-friedo-9β-lanosta-4(28), 7, 14, 24-tetraen-26,23-olide-23-hydroxy-3-oic acid and methyl-3,4-seco-8-(14→13R) abeo-17,13-friedo-9β-lanosta-4(28), 7, 14, 24-tetraen-26,23-olide-23-hydroxy-3-oate, respectively. Structural determination of these compounds were carried out by the spectral studies especially by the two digital (2D)-NMR and high-resolution (HR)-MS experiences.     

Chemical studies on monoterpenoid indole alkaloids from medicinal plant resources <Emphasis Type="Italic">Gelsemium</Emphasis> and <Emphasis Type="Italic">Ophiorrhiza</Emphasis>

We have proved that the plant of origin of “Yakatsu”, one of the ancient medicines stored in Shosoin Repository, is Gelsemium elegans (Loganiaceae). Exhaustive investigation of the alkaloids in this plant as well as its closely related plant, G. sempervirens, resulted in the isolation of more than 50 compounds, including new gelsedine-, sarpagine-, and yohimbane-type alkaloids. Pharmacological study of representative and new Gelsemium alkaloids revealed that the gelsedine-type alkaloids exhibit potent cytotoxic activity against the A431 human epidermoid carcinoma cell line. It was found that Ophiorrhiza pumila (Rubiaceae) produces a remarkable anti-tumor alkaloid, camptothecin, and its related alkaloids, including new compounds that might be the biogenetic precursors of camptothecin. Chemical investigation of callus cultures, regenerated plants, and hairy roots of O. pumila revealed that the regenerated plants and the hairy roots produce almost the same alkaloids, including camptothecin, as do the wild-type plants.     

A new kaempferol trioside from <Emphasis Type="Italic">Solidago altissima</Emphasis> L.

A new kaempferol trioside [kaempferol 3-O-rutinoside 7-O-β-d-apiofuranoside, (1)] was isolated together with nine phenolic compounds, trans-tiliroside (2), caffeic acid (3), chlorogenic acid (4), 3-O-caffeoylquinic acid (5), 4-O-caffeoylquinic acid (6), 3-O-coumaroylquinic acid (7), 4-O-coumaroylquinic acid (8), 3,5-di-O-caffeoylquinic acid (9) and 4,5-dicaffeoylquinic acid (10) from the leaves of Solidago altissima L. The structure elucidations of the compounds were based on the analyses of spectroscopic data.     

A new phenylethanoid glycoside from the fruits of <Emphasis Type="Italic">Callicarpa japonica</Emphasis> Thunb. var. <Emphasis Type="Italic">luxurians</Emphasis> Rehd.

A new phenylethanoid glycoside, named acetyl forsythoside B (1), was isolated from the fruits of Callicarpa japonica Thunb. var. luxurians Rehd. (Verbenaceae) along with forsythoside B (2), brandioside (3), poliumoside (4), actioside (5), and apigenin 7-galacturonide (6). The structures of 1–6 were determined on the basis of spectroscopic data. In addition, the antioxidative activity of 1–4 and 6 was evaluated by the ferric thiocyanate method. All of the tested compounds except 6 exhibited almost the same activity as 3-tert-butyl-4-hydroxyanisole. The radical-scavenging effect of 1–6 on the stable free radical 1,1-diphenyl-2-picrylhydrazyl was also examined. Compounds 1–5 showed almost twice the activity compared to α-tocopherol.     

Hydrolyzable tannins and phenylpropanoid from <Emphasis Type="Italic">Rafflesia kerrii</Emphasis> Meijer (Rafflesiaceae)

Four hydrolyzable tannins, 1,2,4,6-tetra-O-galloyl-β-d-glucopyranoside, 1,2,6-tri-O-galloyl-β-d-glucopyranoside, 1,4,6-tri-O-galloyl-β-d-glucopyranoside; and 1,2,4-tri-O-galloyl-β-d-glucopyranoside, along with a phenylpropanoid glucoside, syringin, were isolated from the flowers of Rafflesia kerrii. The structure elucidations were based on physical data and spectroscopic evidence.     

Polygosumic acid,a new cadinane sesquiterpene from <Emphasis Type="Italic">Polygonum viscosum</Emphasis>, inhibits the growth of drug-resistant <Emphasis Type="Italic">Escherichia coli</Emphasis> and <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> (MRSA) in vitro

Three new sesquiterpenes, 6-hydroxy-7-(1-methylethyl)-3,3a,6,7,8,8a-hexahydroazulene-1,4-dicarboxylic acid methyl ester (1, named viscozulenic acid methyl ester), 7-(1-methylethyl)-3,3a,6,7,8,8a-hexahydroazulene-1,4-dicarboxylic acid 1-methyl ester (2, named viscoazucinic acid) and 3-oxo-1-epi-sclerosporin (3, named polygosumic acid), have been isolated from the chloroform extract of the aerial parts of Polygonum viscosum by reversed-phase preparative high performance liquid chromatography (HPLC). The structures of these compounds were established conclusively by ultraviolet (UV), mass spectrometry (MS) and a series of 1D and 2D nuclear magnetic resonance (NMR) analyses. The anti-bacterial properties of 1–3 against 12 pathogenic bacterial strains have also been assessed by the rapid and robust microtitre-plate-based serial dilution method incorporating resazurin as an indicator of cell growth. Polygosumic acid was the most active among the sesquiterpenes and inhibited the growth of penicillin-resistant Escherichia coli (minimum inhibitory concentration, MIC=0.05 mg/ml) and methicillin-resistant Staphylococcus aureus (MRSA) (MIC=0.10 mg/ml).     

Monoterpene glycoside and flavonoids from <Emphasis Type="Italic">Blumea lacera</Emphasis>

The dichloromethane extract of air-dried leaves of Blumea lacera (Asteraceae) afforded α-pinene-7β-O-β-d-2,6-diacetylglucopyranoside (1), 5,4′-dihydroxy-6,7,3′-trimethoxyflavone (2), and 3,5,4′-trihydroxy-6,7,3′-trimethoxyflavone (3). Compounds 1–3 showed moderate activity against Candida albicans, low activity against Trichophyton mentagrophytes, and were inactive against Aspergillus niger. Compounds 1 and 3 indicated low activity against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus and were inactive against Bacillus subtilis, while 2 was inactive against all four bacteria tested.     

Prenylated xanthones from <Emphasis Type="Italic">Hypericum ascyron</Emphasis>

Three new prenylated xanthones, 1,3,5-trihydroxy-6,7-[2′-(1-methylethenyl)-dihydrofurano]-xanthone (1), 1,3,5-trihydroxy-6,7-[2′-(1-hydroxy-1-methylethyl)-dihydrofurano]-xanthone (2), and 1,3,5-trihydroxy-6-O-prenyl-xanthone (3), together with eight known compounds were isolated from the leaves of Hypericum ascyron. Compound 3 has an O-prenyl moiety, and therefore represents the first reported xanthone to have an O-prenyl moiety from genus Hypericum. The structures of the isolated compounds were established based on spectroscopic data and on a comparison with values for previously identified analogues.     

A new chalcone glycoside from <Emphasis Type="Italic">Sapium sebiferum</Emphasis>

A new chalcone glycoside, having an allenic ester moiety, was isolated together with chalcononaringenin 2′-O-β-D-glucopyranoside from the catkin of Sapium sebiferum. The structure elucidations of chalcone glycosides were based on the analyses of spectroscopic data.     

Studies of the chemical constituents of the flower buds of <Emphasis Type="Italic">Magnolia kobus</Emphasis> and <Emphasis Type="Italic">M. salicifolia</Emphasis>

The constituents of the flower buds of Magnolia kobus DC. and M. salicifolia MAXIM. have been investigated. We isolated and identified six bis-tetrahydrofuran-type and three tetrahydrofuran-type lignan derivatives from M. kobus, and one bis-tetrahydrofuran-type lignan and eight phenylpropanoid-type derivatives from M. salicifolia. The structures of these compounds were elucidated on the basis of chemical and spectroscopic evidence.     

Bridelioside,a new lignan glycoside from <Emphasis Type="Italic">Bridelia glauca</Emphasis> Bl. f. <Emphasis Type="Italic">balansae</Emphasis> (Tucht.) Hatusima

A new lignan glycoside, bridelioside, has been isolated from Bridelia glauca f. balansae. The structure of bridelioside was elucidated be (+)-isolariciresinol 2a-O-α-l-arabinopyranoside on the basis of spectral data.     

A new ceramide from <Emphasis Type="Italic">Ramaria botrytis</Emphasis> (Pers.) Ricken

A new ceramide, (2S,2′R,3R,4E,8E)-N-2′-hydroxyoctadecanoyl-2-amino-9-methyl-4,8-heptadecadiene-1,3-diol (1), was isolated together with four known sterols, 5α,6α-epoxy-3β-hydroxy-(22E)-ergosta-8(14),22-dien-7-one (2), ergosterol peroxide (3), cerevisterol (4) and 9α-hydroxycerevisterol (5), from the fruiting bodies of Ramaria botrytis (Pers.) Ricken (Ramariaceae). The structure of the new compound was elucidated based on spectral data.     

Diacylglycerol acyltransferase-inhibitory compounds from <Emphasis Type="Italic">Erythrina senegalensis</Emphasis>

Inhibition of acyl CoA:diacylglycerol acyltransferase (DGAT) is proposed to be a drug target for the treatment of obesity and type 2 diabetes. Bioassay-guided fractionation of the CH₂Cl₂-soluble extract of the stem bark of Erythrina senegalensis, using an in vitro DGAT enzyme assay, resulted in the isolation of eight known prenylflavonoids, 8-prenylleutone (1), auriculatin (2), erysenegalensein O (3), erysenegalensein D (4), erysenegalensein N (5), derrone (6), alpinumisoflavone (7), and 6,8-diprenylgenistein (8). Compounds 1, 2–4, 6, and 8 inhibited DGAT activity, with IC₅₀ values ranging from 1.1 ± 0.3 to 15.1 ± 1.1 μg/mL. On the basis of the data obtained, we propose isoflavonoids with isoprenyl groups as a novel class of DGAT inhibitors.     

Shosaikoto (a Kampo medicine) modulates changes in cytochrome P450 caused by <Emphasis Type="Italic">Mycobacterium</Emphasis><Emphasis Type="Italic">butyricum</Emphasis> injection

A large number of infectious or inflammatory agents are well known to reduce cytochrome P450-catalyzed drug metabolism in the liver. Changes in the levels of hepatic P450s in infectious or inflammatory diseases can lead to alteration in physiology, therapeutic failure, and disease development. This study was therefore designed to examine the effect of shosaikoto, a Kampo medicine used for treatment of chronic hepatitis and acute flu, on the changes in P450 activity and protein levels following intravenous injection of Mycobacterium butyricum. Intravenous injection of M. butyricum into rats reduced hepatic P450: CYP1A1, 1A2, 2B, and 3A activities and CYP2E1 and 3A2 protein levels. When administered orally to rats for 2 weeks since 1 week before M. butyricum injection, shosaikoto prevented the reduction in CYP1A1, 1A2, 2B, and 3A activities dose dependently and further abrogated the repression of CYP3A2 protein but not CYP2E1 protein. Serum C-reactive protein levels in this rat model were not highly elevated, and neither were significantly influenced by shosaikoto treatment. Taken together, these results suggest that shosaikoto would be capable of modulating the change in hepatic P450 caused by M. butyricum injection and the effect, which might not be brought about by its anti-inflammatory activity but by translational or posttranslational regulation, appears to differ in each P450 isoform.     

Total synthesis and full NMR assignment of ourouparine,a yohimbane-type indole alkaloid isolated from <Emphasis Type="Italic">Gelsemium</Emphasis><Emphasis Type="Italic">sempervirens</Emphasis>

A yohimbane-type indole alkaloid, ourouparine, was found in Gelsemium sempervirens, and its structure was elucidated by spectroscopic analysis and total synthesis.