Hikaru Okabe

Identification of a triterpenoid saponin from a crucifer, Barbarea vulgaris, as a feeding deterrent to the diamondback moth, Plutella xylostella.

Larvae of the diamondback moth, Plutella xylostella, a crucifer specialist, refuse to feed on a crucifer, Barbarea vulgaris, because of the presence of a feeding deterrent, which is extractable with chloroform. We isolated a feeding deterrent from B. vulgaris leaves, by successive fractionations with silica-gel, ODS, i.e., C18 reversed phase, and Sephadex LH-20 column chromatographies, and ODS-HPLC, guided by a bioassay for feeding deterrent activity. The structure of the compound was determined to be a monodesmosidic triterpenoid saponin, 3-O-[O-β-D-glucopyranosyl-(1→4)-β-D-glucopyranosyl]-hederagenin, based on FAB-MS, 1H- and 13C-NMR spectra, and hydrolysis experiments. When the compound was applied to cabbage leaf disks at greater than 0.18 μg/mm2, consumption of the disks by third instars was less than 11% of control disks treated with the solvent alone. Furthermore, all first instars died on the disks treated with the same concentrations. Because the concentration of the compound in the fresh leaves of B. vulgaris was comparable to the effective dose in the cabbage leaf disk tested, we conclude that the unacceptability of B. vulgaris to P. xylostella larvae is primarily due to this saponin.

Antihypertensive substance in seeds of Areca catechu L.

Among various tannins tested, Areca II-5-C, a fraction isolated from seeds of Areca catechu L., showed the most potent angiotensin-converting enzyme (ACE) inhibitory activity in vitro. Its antihypertensive activity was therefore investigated in normotensive and spontaneous hypertensive rats (SHR) after both oral and intravenous (i.v.) administration. The activity was compared with that of captopril (D-3-mercapto-2-methylpropanoyl-L-proline), a potent ACE inhibitor. Oral administration of Areca II-5-C to SHR produced a lasting, dose-related antihypertensive effect, and the responses obtained with doses of 100 and 200 mg/kg were comparable to those of captopril at doses of 30 and 100 mg/kg. Intravenous administration of Areca II-5-C to SHR produced a rapid and marked reduction in blood pressure at doses of 10 and 15 mg/kg. The maximum antihypertensive effect of Areca II-5-C in SHR, at an i.v. dose of 15 mg/kg, was about 5 times as large as that of captopril at the same dose. Although the vasopressor response to norepinephrine and vasodepressor responses to bradykinin and acetylcholine were not appreciably changed by i.v. treatment with Areca II-5-C at a dose of 5 mg/kg, it did produce dose-related inhibition of the pressor responses to angiotensin I and II. It is suggested that Areca II-5-C has favorable properties as a hypotensive drug through its ability to inhibit the pressor responses to both angiotensin I and II.

Resistance in the Plant, Barbarea vulgaris , and Counter-Adaptations in Flea Beetles Mediated by Saponins

Three saponins and two sapogenins had differential effects on food consumption in five near-isogenic flea beetle lines, which differ in their ability to utilize a novel host plant, Barbarea vulgaris (Brassicaceae). The ability to live on this plant is controlled by major, dominant R-genes in the flea beetle, Phyllotreta nemorum (Coleoptera: Chrysomelidae: Alticinae). A susceptible genotype (rr) is unable to live on the plant, whereas resistant genotypes (RR and Rr) can utilize the novel host plant. Among compounds isolated from B. vulgaris, hederagenin cellobioside (hederagenin-3-O-(4-O-β-D-glucopyranosyl)-β-D-glucopyranoside) inhibited feeding, whereas the effect of oleanolic acid cellobioside was much weaker. The aglycones (sapogenins) were inactive. Although hederagenin cellobioside was active against all flea beetle lines, its effect on food consumption was much stronger on the susceptible genotype (rr) compared to the resistant genotype (Rr). Susceptible and resistant flea beetle genotypes were equally sensitive to a non-host saponin, α-hederin (hederagenin-3-O-(2-O-α-L-rhamnopyranosyl)-α-L-arabinopyranoside). These results suggest that R-alleles in flea beetles might be specific adaptations to defensive saponins in B. vulgaris. A possible mechanism of action of the R-alleles might be to encode for an enzyme (e.g. a glucosidase), which is able to cleave glycosidic bonds in hederagenin cellobioside, but not in α-hederin. The potential role of saponins as defensive compounds in B. vulgaris and as targets for counter-adaptations in flea beetles and other insects is discussed.

Novel antiproliferative falcarindiol furanocoumarin ethers from the root of Angelica japonica.

Four novel antiproliferative furanocoumarin ethers of falcarindiol, named japoangelols A (8.5), B (7.2), C (7.4), and D (8.4), were isolated from the root of Angelica japonica together with panaxynol (0.3), falcarindiol (3.2), (9Z)-1,9-heptadecadiene-4,6-diyne-3,8,11-triol (2.2), and 8-acetoxyfalcarinol (3.2). Structures were established from the spectroscopic evidence, and the inhibitory activities (ED50, microgram/ml, shown in the parentheses) were evaluated using the MTT assay.

Liquid chromatography combined with thermospray and continuous-flow fast atom bombardment mass spectrometry of glycosides in crude plant extracts

In crude plant extracts, constituents of biological or pharmaceutical interest often exist in the form of glycosides. Off-line mass spectral investigations of these metabolites require soft ionisation techniques such as desorption chemical ionisation (DCI) or fast atom bombardment (FAB) if information on molecular mass or sugar sequence is desired. In LC-MS, glycosides can be ionised by using thermospray (TSP), continuous-flow fast atom bombardment (CF-FAB) or other interfaces. These techniques are thus potentially applicable to the on-line analysis of glycosides and can be applied to plant extract analysis. Thermospray (TSP) used with ammonium acetate as buffer provides mass spectra similar to those obtained with DCI-MS using NH3 and is potentially applicable to the on-line analysis of relatively small glycosides bearing no more than three sugar units. CF-FAB provides cleaner MS spectra than static FAB due to the lower concentration of the matrix used and can be applied to more polar compounds such as glycosides with a larger number of sugars. The use of a special setup involving post-column addition of the buffer or the matrix and splitting allows LC-UV, TSP LC-MS and CF-FAB LC-MS to be performed with the same standard HPLC conditions. Different crude plant extracts containing various types of glycosides with one to eight sugar units have been analysed by both TSP and CF-FAB. Cardenolides from Nerium odorum (Apocynaceae) and saponins from Swarzia madagascariensis (Leguminosae), Aster scaber and Aster tataricus (Asteraceae) have been studied by LC-MS. The combination of these two interfaces for the HPLC screening of crude plant extracts is discussed.

Triterpenoid saponins from the ground part of Aster ageratoides var. ovatus

Abstract Eight new oleanane-type triterpene glycosides, ageratosides A 1 –A 5 , B 1 , B 2 and C 1 , were isolated from the ground part of Aster ageratoides Turcz. var. ovatus Nakai (Compositae) along with scaberoside A 2 . Their structures were determined based on spectral and chemical evidence as follows. Ageratoside A 1 , 3- O -[ O -β- d -xylopyranosyl-(1→4)-β- d -glucopyranosyl] 2β,3β,16α-trihydroxyolean-12-ene-23,28-dioic acid (zanhic acid) 28- O -β- d -apiofuranosyl-(1→3)- O -(4- O -acetyl)-α- l -rhamnopyranosyl-(1→2)- O -α- l -arabinopyranosyl ester; ageratoside A 2 , 3- O -[ O -β- d -glucopyranosyl-(1→4)-β- d -glucopyranosyl] zanhic acid 28- O -β- d -apiofuranosyl-(1→3)- O -(4- O -acetyl)-α- l -rhamnopyranosyl-(1→2)- O -α- l -arabinopyranosyl ester; ageratoside A 3 , 3- O -[ O -β- d -xylopyranosyl-(1→4)-β- d -glucopyranosyl] zanhic acid 28- O -α- l -arabinopyranosyl-(1→3)- O -(4- O -acetyl)-α- l -rhamnopyranosyl-(1→2)- O -α- l -arabinopyranosyl ester; ageratoside A 4 , 3- O -β- d -glucopyranosyl zanhic acid 28- O -α- l -arabinopyranosyl-(1→3)- O -(4- O -acetyl)-α- l -rhamnopyranosyl-(1→2)- O -α- l -arabinopyranosyl ester; ageratoside A 5 , 3- O -β- d -glucopyranosyl zanhic acid 28- O -β- d -apiofuranosyl-(1→3)- O -(4- O -acetyl)-α- l -rhamnopyranosyl-(1→2)- O -α- l -arabinopyranosyl ester; ageratoside B 1 , 3- O -β- d -glucopyranosyl 2β,3β-dihydroxyolean-12-ene-23,28-dioic acid (medicagenic acid) 28- O -β- d -glucopyranosyl-(1→6)- O -β- d -glucopyranosyl ester; ageratoside B 2 , 3- O -[ O -β- d -xylopyranosyl-(1→4)-β- d -glucopyranosyl] medicagenic acid 28- O -β- d -xylopyranosyl-(1→3)- O -α- l -rhamnopyranosyl-(1→2)- O -α- l -arabinopyranosyl ester; and ageratoside C 1 , 3- O -[ O -β- d -xylopyranosyl-(1→4)-β- d -glucopyranosyl] 2β,3β,16α,21β-tetrahydroxyolean-12-ene-23,28-dioic acid 21,28-lactone.

Structures of momordicosides F1, F2, G, I, K and L, novel cucurbitacins in the fruits of Momordica charantia L.

Two bitter cucurbitacins, momordicosides K and L, and four non-bitter cucurbitacins, momordicosides F1, F2, G and I, were isolated from the immature fruits of Momordica charantia L. (Cucurbitaceae) and their structures were elucidated.

Antitumor agents 171. Cytotoxicities of lobatosides B, C, D, and E, cyclic bisdesmosides isolated from Actinostemma lobatum maxim

Abstract Cytotoxicities for lobatosides B—E and actinostemmosides B—F, isolated from Actinostemma lobatum , were evaluated against a panel of ca 60 human cancer cell lines. Lobatosides B—E ( 1–4 ) were cytotoxic (GI 50 ≤ 1 × 10 −4 M) against all tumor cell lines; 4 showed potent cytotoxicity especially against A-549, SK-MEL-5, and SW-620 cell lines with GI 50 values of 0.14, 0.14, and 0.36 μM, respectively.

Macrocyclic pyrrolizidine alkaloids from Parsonsia laevigata

Abstract Parsonsianidine, a new minor macrocyclic pyrrolizidine alkaloid having two ethyl side-chains at C-11 and C-20, was isolated along with parsonsianine from the leaves of Parsonsia laevigata . Its structure was determined by spectral analyses. 17-Methylparsonsianidine, having the same plane structure as spiranine, was also identified.

Screening of promising chemotherapeutic candidates against human adult T-cell leukemia/lymphoma from plants: active principles from Physalis pruinosa and structure–activity relationships with withanolides

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-cell lymphotropic virus type I (HTLV-1). Clinical manifestations of ATL range from smoldering to chronic, lymphoma and acute subtypes. Patients with acute and lymphoma-type ATL require therapeutic intervention. Conventional chemotherapeutic regimens used against other malignant lymphoma have been administered to ATL patients, but the therapeutic outcomes of acute and lymphoma-type ATL remain very poor. In this study, 214 extracts from 162 plants belonging to 65 families were screened for the purpose of elucidating the anti-proliferative effect against HTLV-1-infected T-cell lines. Extracts from aerial parts of Physalis pruinosa showed potent inhibitory effect. We isolated five withanolides from the extracts by activity-guided fractionation and examined the structure–activity relationships. The presence of a 5β,6β-epoxy function is suggested to be essential for the activity, and the most active principle showed selective toxicity to HTLV-1-infected T-cell lines.