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Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) plays a crucial role in the optimal treatment strategy for patients with coronary heart disease. We tested the feasibility of feature extraction from MPI using a deep convolutional autoencoder (CAE) model.Eight hundred and forty-three pairs of stress and rest myocardial perfusion images were collected from consecutive patients who underwent cardiac scintigraphy in our hospital between December 2019 and February 2022. We trained a CAE model to reproduce the input paired image data, so as the encoder to output a 256-dimensional feature vector. The extracted feature vectors were further dimensionally reduced via principal component analysis (PCA) for data visualization. Content-based image retrieval (CBIR) was performed based on the cosine similarity of the feature vectors between the query and reference images. The agreement of the radiologist's finding between the query and retrieved MPI was evaluated using binary accuracy, precision, recall, and F1-score.A three-dimensional scatter plot with PCA revealed that feature vectors retained clinical information such as percent summed difference score, presence of ischemia, and the location of scar reported by radiologists. When CBIR was used as a similarity-based diagnostic tool, the binary accuracy was 81.0%.The results indicated the utility of unsupervised feature learning for CBIR in MPI.

During the course of our studies towards the identification of promising chemotherapeutic candidates from plants against two human T-cell lymphotropic virus type I-infected T-cell lines (MT-1 and MT-2), we screened 17 extracts from 9 rutaceous plants against MT-1 and MT-2 cells. The extracts from the aerial parts and roots of Boenninghausenia japonica, as well as the leaves and roots of Ruta graveolens showed potent antiproliferative effects. After activity-guided fractionation, we isolated 44 compounds from two rutaceous plants, including three new compounds (1-3), which were classified into 26 coumarin analogs (13 coumarins, 8 furanocoumarins, 4 dihydrofuranocoumarins and one dihydropyranocoumarin), 15 alkaloid analogs (7 quinolone alkaloids, 4 acridone alkaloids, 3 furanoquinoline alkaloids and one tetrahydroacridone alkaloid) and 3 flavonoid glycosides. Structure-activity relationship studies were also evaluated. The coumarin compounds (2, 3 and 7-9) bearing a 3-dimethylallyl moiety showed potent activity. Similarly, of all the furanocoumarins evaluated in the current study, compound 17 bearing a 3-dimethylallyl group also showed potent activity. A dihydrofuranocoumarin (27) bearing a 3-dimethylallyl moiety showed the most potent activity. Following 27, compound 28 showed potent activity. These results therefore suggested that the presence of a 3-dimethylallyl moiety was important to the antiproliferative activity of these coumarin analogs.

Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature peripheral T lymphocytes caused by human T-cell lymphotropic virus type 1 (HTLV-1). There are an estimated 5 million to 20 million HTLV-1-infected individuals worldwide; their lifetime risk of developing ATL is 3-5 %, and high HTLV-1 proviral loads have been shown to be an independent risk factor. Although conventional chemotherapeutic regimens used against other malignant lymphomas have been administered to ATL patients, the prognosis is often poor. In previous studies, we screened 459 extracts from 344 plants to isolate components exhibiting antiproliferative activity against HTLV-1-infected T-cell lines (MT-1 and MT-2). In our continuing search for potential anti-HTLV-1 natural products, 15 extracts of Asclepiadaceae plants were further tested against MT-1 and MT-2 cells. The MeOH extract of aerial parts of Tylophora tanakae showed antiproliferative activity. Activity-guided fractionation resulted in the isolation of 6 phenanthroindolizidine alkaloids (including a new compound), and we examined their antiproliferative activity against MT-1 and MT-2 cells. The EC50 value of some of the alkaloids was in the low nanomolar range, comparable to that of the clinically used antineoplastic drug doxorubicin. Structure-activity relationship analyses suggested that a 14β-hydroxy moiety is essential for activity against HTLV-1-infected T cells. In contrast, the presence of a 2-methoxy moiety, a 7-methoxy moiety, or an N-oxide moiety appears to reduce the potency of the antiproliferative activity against HTLV-1-infected T cells.

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.

In order to clarify the efficacy of natural-occurring hepatoprotective flavonoids and related miscellaneous compounds, we have investigated the hepatoprotective activity of 41 phenolic compounds on human liver-derived HepG2 cells and evaluated their structure-activity relationships. The hepatoprotective activity of catechin (cyanidanol), which has been used to treat chronic hepatitis, was almost equal to that of glycyrrhizin at 200 μM. The structure-activity relationships of flavanol derivatives as revealed by this investigation suggest that (1) the configuration of the hydroxy group at C-3 does not affect the hepatoprotective activity; (2) the pyrogallol and catechol groups in the B-ring are almost comparable in terms of hepatoprotection; (3) the galloyl group is a key factor for enhancing hepatoprotective activity; (4) the free carboxyl group of gallic acid reduces hepatoprotective activity. The common structural features of the most potent hepatoprotective phenolic compounds are summarized.

Two glucuronides (4'-O-, and 7-O-) and a glucuronyl (7-O-) sulfate (4'-O-) of genistein, two glucuronides (4'-O-, and 7-O-) and a glucuronyl (7-O-) sulfate (4'-O-) of daidzein, 7-O-glucuronides of glycitein, dihydrodaidzein and O-desmethylangolensin were isolated from the urine of volunteer subjects fed soy bean curds (Tofu). The estrogenic activities, i.e., i) the effect on the estrogen-dependent growth of MCF-7 cells, ii) the binding ability to human estrogen receptors (hERs) alpha and beta, and iii) the effect on hER-dependent beta-galactosidase induction, of these isoflavone metabolites were examined. Two synthetic isoflavone aglycones (dihydrodaidzein and O-desmethylangolensin) and four synthetic sulfates (4'-O- and 4'-, 7-di-O-) of genistein and daidzein were also studied for their estrogenic activities for the purpose of comparison. With respect to estrogenic acivity, the tested isoflavone metabolites were classified into three groups. The first group shows a very poor stimulatory effect toward the growth of MCF-7 cells, binding activity, and beta-galactosidase induction. The sulfates belong to this group. The second group shows a moderate binding activity but poor stimulation and beta-galactosidase induction. Some glucuronyl conjugates belong to this group. The last group shows a moderate stimulation and beta-galactosidase induction but poor binding activity. A mixed type of conjugates having glucuronyl and sulfony moieties belong to this group.

Eighteen main compounds, including four norsesquiterpenoids (1?4) and 14 phenolic compounds (5?18) isolated previously from Phyllanthus emblica, together with a main constituent, proanthocyanidin polymers (19) identified at this time from the roots, were estimated for their antiproliferative activities against MK-1 (human gastric adenocarcinoma), HeLa (human uterine carcinoma), and B16F10 (murine melanoma) cells using an MTT method. All of the phenolic compounds including the major components 5?8 from the fruit juice, 8, 9, and 12 from the branches and leaves, and 19 from the roots showed stronger inhibition against B16F10 cell growth than against HeLa and MK-1 cell growth. Norsesquiterpenoid glycosides 3 and 4 from the roots exhibited significant antiproliferative activities, although their aglycon 1 and monoglucoside 2 showed no inhibitory activity against these tumor cells., Biological & Pharmaceutical Bulletin v.27(2) p.251-255, 2004

The effects of soyasapogenol B, sophoradiol, their glucuronides, and glycyrrhizin on the hepatotoxicity of tert-butyl hydroperoxide (t-BuOOH) in a human-liver-derived cell line (HepG2 cells) were investigated. Glycyrrhizin showed significant dose-dependent protective effects against the cytotoxicity of t-BuOOH. Among soyasapogenol B and its glucuronides, the monoglucuronide showed the most potent hepatoprotective activity, followed by soyasapogenol B itself. Soyasaponin III was weakly protective, while soyasaponin I increased the toxicity of t-BuOOH. Among sophoradiol and its glucuronides, sophoradiol itself showed the most potent hepatoprotective activity, which was equal to glycyrrhizin, while the monoglucuronide and kaikasaponin III showed an increase in cytotoxicity. These results were considerably different from those reported previously on the protective effects of these compounds using primary cultures of immunologically injured rat liver cells. Consequently, the hepatoprotective action of the triterpene derivatives investigated would be different in HepG2 cells and in rat primary hepatocyte cultures.

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.

The flavonoid fraction from the leaves of Lantana montevidensis Briq. (Verbenaceae) showed antiproliferative activity against human gastric adenocarcinoma (MK-1, GI50: 12 microg/ml), human uterus carcinoma (HeLa, 5 microg/ml), and murine melanoma (B16F10, 5 microg/ml) cells in vitro. Bioactivity-guided chemical investigation of the fraction has resulted in the isolation of apigenin (10) and ten 5,6,7-oxygenated flavones: cirsilineol (1), eupatorin (2), 5,4'-dihydroxy-6,7,3',5'-tetramethoxyflavone (3), 5,6-dihydroxy-7,3',4'-trimethoxyflavone (4), 5,6,4'-trihydroxy-7,3',5'-trimethoxyflavone (5), 5,6,3'-trihydroxy-7,4'-dimethoxyflavone (6), 5,3',4'-trihydroxy-6,7,5'-trimethoxyflavone (7), cirsiliol (8), hispidulin (9), and eupafolin (11). Antiproliferative activity of the isolated flavones, some other related flavones (luteolin, baicalein, 6-hydroxyluteolin, pectolinarigenin, jaceosidin, desmethoxycentaureidin, eupatilin, and chrysin) from other plant materials, and synthetic 6- and 7-methoxyflavones was evaluated, and the structure-activity relationships were examined.

Crude extracts of Mexican medicinal plants were screened for trypanocidal activity against Trypanosoma cruzi, which is the etiological agent for Chagas' disease, one of the most serious protozoan diseases in Latin America. There were 43 kinds of methanolic and other organic extracts from 39 plants which were examined by the preliminary screening test to see immobilization of epimastigotes of T. cruzi in vitro. Eighteen of them showed activity at the concentration of 2 mg/ml after incubation for 2 h, while 13 showed activity at the concentration of 1 mg/ml after incubation for 48 h. Among them, the MeOH extract of roots of Aristolochia taliscana (Aristolochiaceae), locally known as "Guaco," immobilized all the epimastigotes even at lower concentration of 0.5 mg/ml (48 h). In order to identify principal compounds for this activity, the MeOH extract of Guaco was subjected to bioassay-guided fractionation. From the active fractions, four neolignans, eupomatenoid-7 (1), licarin A (2), eupomatenoid-1 (5) and licarin B (6), and two lignans, austrobailignan-7 (3) and fragransin E1 (4) were isolated. Compounds 1-4 immobilized all the epimastigotes at the minimum concentration of 25-75 microg/ml after incubation for 48 h, while compounds 5 and 6 were inactive. Corresponding concentration of gossypol, berberine chloride and harmine was 280 microg/ml, 300 microg/ml and >500 microg/ml, respectively.

Based on our previous finding that 3-O-acyl-betulinic and -oleanolic acids, especially the 3-O-(3',3'-dimethyl)-succinyl derivatives (2 and 4), demonstrated potent anti-HIV activity [EC(50)0.00035 and 0.00086 microM; therapeutic index (TI)20 000 and 22 326, respectively], several 3-O-acyl-ursolic acids were prepared and evaluated for anti-HIV activity. Ursolic acid (6) was equipotent (EC(50) 4.4 microM) with oleanolic acid (EC(50) 3.7 microM), although it was slightly toxic (IC(50) 14.3 microM, TI 3.3). 3-O-Diglycoryl-ursolic acid (10) demonstrated relatively potent anti-HIV activity with an EC(50) of 0. 31 microM and a TI of 155.5. In contrast, 3-O-(3', 3'-dimethylsuccinyl)-ursolic acid (8), which is analogous to the extremely potent anti-HIV betulinic acid and oleanolic acid derivatives 2 and 4, displayed only weak anti-HIV activity (EC(50) 2.1 microM, TI 23.6).

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.

Sixteen glycosides of polyoxypregnanes, including two new pregnanes, isokidjoladinin and isotemontosin, were isolated form the leaves and caules of Marsdenia tomentosa collected in Fukuoka. The structures of fourteen new glycosides were elucidated and named marstomentosides A-N.

The CHCl3 extract of the root of Angelica japonica showed high inhibitory activity against human gastric adenocarcinoma (MK-1) cell growth. From this extract, a new furanocoumarin named japoangelone and four furanocoumarin ethers of falcarindiol, named japoangelols A-D, were isolated together with caffeic acid methyl ester, four polyacetylenic compounds (panaxynol, falcarindiol, 8-O-acetylfalcarindiol, and (9Z)-1,9-heptadecadiene-4,6-diyne-3,8,11-triol), eight coumarins (osthol, isoimperatorin, scopoletin, byakangelicin, xanthotoxin, bergapten, oxypeucedanin methanolate, and oxypeucedanin hydrate), and two chromones (3'-O-acetylhamaudol, and hamaudol). The structures of the new isolates were determined based on spectral evidence. The ED50 of isolates against MK-1, HeLa, and B16F10 cell lines are reported.

The constituents in the fruit of Anthriscus sylvestris HOFFM. were investigated, and four ligans [deoxypodophyllotoxin, morelensin, (-)-deoxypodorhizone, and (-)-hinokinin], one phenylpropanoid [1, (3', 4'-dimethoxyphenyl)-1ξ-hydroxy-2-propene], two phenylpropanoid esters [3', 4'-dimethoxycinnamyl (Z)-2-angeloyloxymethyl-2-butenonate and 3', 4'-dimethoxycinnamyl (Z)-2-tigloyloxymethyl-2-butenoate], and one polyacetylenic compound (falcarindiol) were isolated. Their antiproliferative activity against MK-1, HeLa and B16F10 cell lines is reported.

Methanol extracts of 36 samples of 21 Umbelliferae plants were screened for polyacetylenic compounds using the ELISA for panaxytriol, and their antiproliferative activity was checked by MTT assay using the tumor cell lines MK-1, HeLa and B16F10. The presence of antiproliferative polyacetylenes was suggested in Angelica acutiloba (fruit), Anethum graveolens (root), Bupleurum rotundifolium (fruit), Carum carvi (fruit and root), Coriandrum sativum (fruit), Cryptotaenia japonica (leaf), Glehnia littoralis (fruit), Heracleum moellendorffii (root) and Torilis japonica (fruit). Panaxynol and falcarindiol were successfully isolated from the root of Heracleum moellendorffii as antiproliferative polyacetylenes.

Six bisdesmosidic bayogenin saponins, named tacacosides A1, A2, B1, B2, B3 and C, were isolated from the fruit and aerial parts of Sechium pittieri (COGN.) C. Jeffrey and S. talamancense (WUNDERLIN) C. Jeffrey, Costa Rican cucurbitaceae plants. Their structures were elucidated on spectral and chemical evidence as follows. Tacacoside A1: 3-O[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl]bayogenin 28-O-(alpha-L-rhamnopyranosyl- (1-->3)-beta-D-xylopyranosyl-(1-->4)-beta-D-apiofuranosyl-(1-->3)] - alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl) ester, tacacoside A2: 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl]bayogenin 28-O-(alpha-L-rhamnopyranosyl- (1-->3)-beta-D-xylopyranosyl-(1-->4)-[beta-D-xylopyranosyl-(1-->3)]-a lph a-L- rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl) ester, tacacoside B1: 3-O-[beta-D-glucopyranosyl]bayogenin 28-O-(alpha-L-rhamnopyranosyl-(1-->3)-beta-D-xylopyranosyl- (1-->4)-[beta-D-apiofuranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1- ->2)-alpha- arabinopyranosyl) ester, tacacoside B2: 3-O-[beta-D-glucopyranosyl]bayogenin 28-O-(alpha-L-rhamnopyranosyl-(1-->3)- beta-D-xylpyranosyl-(1-->4)-[beta-D-xylopyranosyl- (1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl) ester, tacacoside B3: 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl] bayogenin 28-O-[alpha-L-rhamnopyranosyl-(1-->3)-beta-D-xylopyranosyl- (1-->4)-alpha-L-rhamnopyranosyl- (1-->2)-alpha-L-arabinopyranosyl] ester, and tacacoside C: 3-O-[beta-D-glucopyranosyl]bayogenin 28-O-[alpha-L-rhamnopyranosyl- (1-->3)-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)- alpha-L-arabinopyranosyl] ester. These saponins showed moderate antiproliferative activity (ED50:10-74 micrograms/ml) against MK-1, HeLa and B16F10 cells.

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.

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.

The bitter constituents in the root of Cayaponia tayuya (VELL.) COGN. were investigated, and 24 29-norcucurbitacin glucosides, named cayaponosides, were isolated. Among the 24 29-norcucurbitacin glucosides, named cayaponosides, isolated from the root of Cayaponia tayuya (VELL.) COGN., structures of cayaponosides A1, B6a, B6b, C3 D3a and C3b were determined based mainly on spectral analyses. They are all 3-O-glucosides of 29-nor-2, 11-dioxocucurbita-3, 5-diene, only different in side chain structure.

Steroidal constituents from the roots and stems of Asclepias fruticosa L. were investigated separately. From the roots, twelve pregnane pentaosides and uzarigenin beta-sophoroside were isolated together with three known coroglaucigenin and corotoxigenin glycosides. Pregnane glycosides were composed of ikemagenin or kidjolanin as an aglycone, and D-digitoxose, D-cymarose, D-oleandrose and terminal D-glucose as component sugars. Among the constituents from the stems, cardenolides show a similar pattern to those from leaves. 17 alpha-Hydroxycalactin and 17 alpha-hydroxyafroside were newly obtained along with known doubly linked and normally linked glycosides. Two pregnane glycosides and uzarigenin beta-sophoroside obtained from the roots were also isolated.

The bitter constituents in the root of Cayaponia tayuya (VELL.) COGN. were investigated, and 24 29-norcucurbitacin glucosides, named cayaponosides were isolated. Among them, the structures of cayaponosides A, A3, A4, A6, B, B2, B3, B4, C, C2, C5a, D and D1 were determined based mainly on spectral analyses. They are all glucosides of 29-nor-1, 2, 3, 4, 5, 10-hexadehydrocucurbitacins, different only in side chain structure.

The MeOH extract of the roots of Inula helenium showed a high inhibitory activity for cell growth against MK-1, HeLa and B16F10 cell lines. Significant activity was found in the hexane-soluble fraction. From the hexane-soluble fraction, seven sesquiterpenes, namely, one germacrane (4beta,5alpha-epoxy-1(10),11(13)-germacradiene-8,12-olide), one elemane (igalane), and five eudesmanes (alantolactone, isoalantolactone, 11alpha,13-dihydroalantolactone, 11alpha,13-dihydro-isoalantolactone, 5-epoxyalantolactone) were isolated. In vitro antiproliferative activities of the isolates against MK-1, HeLa and B16F10 cells are reported.

Epidemiological studies have suggested that the consumption of green tea provides protection against stomach cancer. Fractionation of green tea extract, guided by antiproliferative activity against human stomach cancer (MK-1) cells, has resulted in the isolation of six active flavan-3-ols, epicatechin (EC), epigallocatechin (EGC), epigallocatechin gallate (EGCg), gallocatechin (GC), epicatechin gallate (ECg), gallocatechin gallate (GCg), together with inactive glycosides of kaempferol and quercetin. Among the six active flavan-3-ols, EGCg and GCg showed the highest activity, EGC, GC, ECg followed next, and the activity of EC was lowest. These data suggest that the presence of the three adjacent hydroxyl groups (pyrogallol or galloyl group) in the molecule would be a key factor for enhancing the activity. Since reactive oxygen species play an important role in cell death induction, radical scavenging activity was evaluated using the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical. The order of scavenging activity was ECg?EGCg?EGC?GC?EC. The compounds having a galloyl moiety showed more potent activity. The contribution of the pyrogallol moiety in the B-ring to the scavenging activity seemed to be less than that of the galloyl moiety., Biological & Pharmaceutical Bulletin v.25(9) p.1238-1240, 2002

The antiproliferative constituents in the MeOH extracts of the aerial parts of Lippia dulcis Trev. and Lippia canescens Kunth (Verbenaceae) were investigated. Activity-guided chemical investigation of the MeOH extracts resulted in the isolation of the three bisabolane-type sesquiterpenes [(+)-hernandulcin (1), (-)-epihernandulcin (2), and (+)-anymol (3)] and four phenylethanoid glycosides [acteoside (4), isoacteoside (5), martynoside (6), and a new diacetylmartynoside (7)] from the former, and four phenylethanoid glycosides [acteoside (4), isoacteoside (5), arenarioside (8), and leucosceptoside A (9)] and three flavones [desmethoxycentaureidin (10), eupafolin (11), and 6-hydroxyluteolin (12)] from the latter. Antiproliferative activity of the isolated compounds against murine melanoma (B16F10), human gastric adenocarcinoma (MK-1), and human uterine carcinoma (HeLa) cells was estimated. (+)-Anymol (3), acteoside (4), isoacteoside (5), arenarioside (8), eupafolin (11), and 6-hydroxyluteolin (12) had GI50 values of 10-16 microM against B16F10 cell. Desmethoxycentaureidin (10) and eupafolin (11) showed high inhibitory activity against HeLa cell growth (GI50 9 microM, and 6 microM, respectively).

The MeOH extract of the seeds of Rhynchosia volubilis (Leguminosae) showed antiproliferative activity against human gastric adenocarcinoma [MK-1, 50% growth inhibition (GI50): 25 μg/ml], human uterus carcinoma (HeLa, GI50: 30 μg/ml), and murine melanoma (B16F10, GI50: 8 μg/ml) cells. Bioactivity-guided fractionation resulted in the isolation of gallic acid methylester (1), gallic acid (2), 7-O-galloylcatechin (3), 1,6-di-O-galloylglucose (4), 1-O-galloylglucose (5), and trigalloylgallic acid (6), and their antiproliferative activity was estimated. All showed much stronger inhibition against B16F10 cell growth than against HeLa and MK-1 cell growth. Compound 2 and its tetramer (6) with a free carboxyl group showed higher activity than those which did not have a free carboxyl group. In relation to the gallic acid tetramer (6), two gallic acid dimers (ellagic acid and dehydrodigallic acid) and trimers (tergallic acid dilactone and flavogallonic acid dilactone) were tested for their activity, and compared with those of the isolates., Biological & Pharmaceutical Bulletin v.24(12) p.1443-1445, 2001

Four isomers of 3,28-di-O-(dimethylsuccinyl)-betulin were prepared and evaluated for anti-HIV activity against HIV-1 replication in H9 lymphocyte cells. 3-O-(3′,3′-Dimethylsuccinyl)-28-O-(2″,2″-dimethylsuccinyl)-betulin (11) was the most potent anti-HIV compound with an EC50 value of 0.00087 μM and a TI value of 42,400.

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.

Sixteen glycosides of polyoxypregnanes, including two new pregnanes, isokidjoladinin and isotemontosin, were isolated form the leaves and caules of Marsdenia tomentosa collected in Fukuoka. The structures of fourteen new glycosides were elucidated and named marstomentosides A-N.

Two new gypsogenin glycosides, named lobatosides I and J, and one oleanolic acid glycoside, lobatoside K, were isolated from the seed of Actinostemma lobatum MAXIM. (Cucurbitaceae), and thier structures were elucidated to be as follows based on chemical and spectral evidence.Lobatoside I : 3-O-[O-β-D-galactopyranosyl-(1→2)-β-D-glucopyranosyluronic acid]gypsogenin 28-{O-β-D-glucopyranosyl-(1→3)-[O-β-D-xylopyranosyl-(1→4)]-O-α-L-rhamnopyranosyl-(1→2)-β-D-fucopyranosyl}ester.Lobatoside J : 3-O-[O-β-D-galactopyranosyl-(1→2)-β-D-glucopyranosyluronic acid]gypsogenin 28-{O-β-D-xylopyranosyl-(1→3)-O-β-D-xylopyranosyl-(1→4)-[O-β-D-glucopyranosyl-(1→3)]-O-α-L-rhamnopyranosyl-(1→2)-β-D-fucopyranosyl}ester.Lobatoside K is an oleanolic acid glycoside. The structure of the sugar moiety is the same as that of lobatoside I.

Three new withanolides, physagulins A (1), B (2) and D (3), were obtained from the methanolic extract of the fresh leaves and stems of Physalis angulata L. (Solanaceae). Their structures were established as (20S, 22R)-15α-acetoxy-5β, 6β-epoxy-14α-hydroxy-1-oxowitha-2, 16, 24-trienolide (1), (20S, 22R)-15α-acetoxy-5α-chloro-6β, 14α-dihydroxy-1-oxowitha-2, 16, 24-trienolide (2) and (20S, 22R)-1α, 3β, 27-trihydroxywitha-5, 24-dienolide 3-O-β-D-gluco-pyranoside (3) by spectroscopic means.

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-beta-D-glucopyranosyl)-beta-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, alpha-hederin (hederagenin-3-O-(2-O-alpha-L-rhamnopyranosyl)-alpha-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 alpha-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.

Four new echinocystic acid 3, 28-O-bisdesmosides, scaberosides A1, A2, A3 and A4, were isolated together with aster saponin Ha, aster saponin Hb and foetidissimoside A from the polar glycoside fraction of the root of Aster scaber THUNB. (Compositae) as their methyl esters, and their structures were determined based on spectral and chemical evidence. Scaberosides have a common prosapogenin, echinocystic acid 3-O-β-D-glucopyranosiduronic acid, and differ in the structures of the ester-linked sugar moieties. Scaberoside A1 is a 28-[O-β-D-apiofuranosyl-(1→3)-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl] ester, A2, a 28-[O-β-D-xylopyranosyl-(1→4)-O-α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranosyl] ester, A3, a 28-{O-β-D-apiofuranosyl-(1→3)-[O-β-D-xylopyranosyl-(1→4)-]-O-α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranosyl]ester, A4, a -28-{O-β-D-xylopyranosyl-(1→3)-[O-β-D-xylopyranosyl-(1→3)-O-β-D-xylopyranosyl-(1→4)-]-O-α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranosyl} ester of the prosapogenin.

Six oleanolic aicd glucuronide saponins, scaberosides B1, B2, B3, B4, B5 and B6 were isolated from the root of Aster scaber THUNB. (Compositae) as their methyl esters, and their structures were determined based on spectral and cheimical evidence. Scaberosides have a common prosapogenin structure, oleanolic acid 3-O-glucopyranosiduronic acid, and differ in the structures of the 28-O-linked sugar moieties.Scaberoside B1 is a 28-[α-L-arabinopyranosyl] ester, scaberoside B2, a 28-[β-D-xylopyranosyl] ester, scaberoside B3, a 28-[O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl] ester, and scaberoside B4, a 28-[O-α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranosyl] ester, scaberoside B5, a 28-[O-β-D-xylopyranosyl-(1→4)-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl] ester, scaberoside B6, a 28-{O-β-xylopyranosyl-(1→4)-O-α-L-rhamnopyranosyl-(1→2)-β-D-xylopyranosyl] ester of the prosapogenin.

From the seeds of Luffa acutangula ROXB. (Cucurbitaceae), two 3, 28-O-bisdesmosidic heptaglycosides of oleanolic acid, named acutosides H and I, were isolated and their structures were elucidated. Acutosides H and I have the same prosapogenin structure, oleanolic acid 3-O-[O-α-L-arabinopyranosyl-(1→3)-β-D-glucopyranosyluronic acid] and differ in the structures of the ester-linked sugar moieties. Acutoside H is a 28-O-[O-β-D-xylopyranosyl-(1→3)-O-β-D-xylopyranosyl-(1→4)-[O-β-D-xylopyranosyl(1→3)]-O-α-L-rhamopyranosyl-(1→2)-α-L-arabinopyranosyl] ester, and acutoside I is a 28-O-[O-α-L-arabinopyranosyl-(1→3)-O-β-D-xylopyranosyl-(1→4)-[O-β-D-xylopyranosyl-(1→3)]-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl] ester.

Three neutral 3, 28-O-bisdesmosidic glycosides of quillaic acid, named bubiosides D, E and F, were isolated from the tuber of Thladiantha dubia BUNGE (Cucurbitaceae). Their structures were elucidated on the basis of chemical and spectral evidence.All dubiosides have a common prosapogenin structure, 3-O-[O-β-D-glucopyranosyl-(1→3)-[O-β-D-galactopyranosyl-(1→2)]-β-D-glucopyranosyl]-quillaic acid, and differ only in the structures of the estr-linked sugar moieties. Dubioside D is a 28-[O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl] ester, dubioside E, a 28-[O-β-D-xylopyranosyl-(1→4)-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl] ester and dubioside F, a 28-[O-β-D-xylopyranosyl-(1→3)-O-β-D-xylopyranosyl-(1→4)-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl] ester of the prosapogenin.

The MeOH extract of the fruits of Bupleurum rotundifolium showed inhibitory activity against human gastric adenocarcinoma (MK-1) cell growth. Bioactivity-guided fractionation of the MeOH extract led to the isolation of four new triglycosides of 13beta,28-epoxy oleanane-type triterpenes, named rotundiosides O, Q, S and T; 12 new glycosides of oleanane-type triterpenes, named rotundiosides J-N, P, R, U-Y, and others; echinocystic acid 3-O-sulfate; and three known oleanane-type triterpene glycosides, rotundiosides A, F and G. The structures of the new isolates were determined based on chemical and spectroscopic evidence. The GI(50) of isolates against MK-1, HeLa and B16F10 cell lines are reported.

NMR signal reassignments for a cytotoxic glycosphingolipid compound, 2, β-O-D-glucopyranosyl-2-(2'-hydroxy-Z-6'-enecosamide)sphingosine, isolated from an ethanolic extract of the herb Murdannia loriformis, have been achieved by use of FAB-MS, and 1D and 2D 1H and 13C NMR. The amount of 2 in the herb juice was quantitatively determined by use of a validated HPLC method (RP-18, MeOH-H2O, UV detection at 210 nm). The immunomodulatory effect of the herb juice and of 2 was proved by means of in vitro cellular immunological assays. Compound 2 at a concentration of 13 nmol L-1 stimulated PBMC proliferation and increased the CD 3,4:CD 3,8 ratio in T lymphocytes.

The antiproliferative constituents in the MeOH extract from the aerial parts of Centella asiatica were investigated. Activity-guided fractionation of MeOH extract resulted in the isolation of ursolic acid lactone, ursolic acid, pomolic acid, 2alpha,3alpha-dihydroxyurs-12-en-28-oic acid, 3-epimaslinic acid, asiatic acid, corosolic acid, and rosmarinic acid. Antiproliferative activity of the isolated compounds against human gastric adenocarcinoma (MK-1), human uterine carcinoma (HeLa), and murine melanoma (B16F10) cells was estimated.