A new acyclic diterpene acid and bioactive compounds from Knema glauca.

Investigation of the chemical constituents of the fruits of Knema glauca (Myristicaceae) yielded a new acyclic diterpene acid, named glaucaic acid 4, together with four acylphenols, including 1-(2,6-dihydroxyphenyl) tetradecan-1-one 1, malabaricone A 6, dodecanoylphloroglucinol 7 and 1-(2,4,6-trihydroxyphenyl)-9-phenylnonan-1-one 8, two lignans sesamin 2 and asarinin 3, and a flavan, myristinin D 5. In addition, myristinin A 9 and (+/-)-7,4'-dihydroxy-3'-methoxyflavan 10 were isolated from its leaves and stems, respectively. When tested against small-cell lung cancer (NCI-H187), epidermoid carcinoma (KB) and breast cancer (BC) cell lines, compounds 1, 6-8 and 10 displayed weak to moderate cytotoxicity. The acylphenols 6-8 displayed antituberculosis activity against the microbe Mycobacterium tuberculosis with MIC values of 25, 50 and 100 microg/mL, respectively, and antiviral activity against herpes simplex virus type 1, with 7 as the most active compound (IC(50) = 3.05 microg/mL). Malabaricone A 6 was also active against the malarial parasite Plasmodium falciparum with an IC(50) value of 2.78 microg/mL.

Cytotoxic C-benzylated chalcone and other constituents of Ellipeiopsis cherrevensis.

A new natural C-benzylated chalcone, 2',4'-dihydroxy-3'-(2-hydroxybenzyl)-6'-methoxychalcone (2), along with two other flavonoids, tiliroside and kaempferol 3-O-rutinoside, and an oxoaporphine alkaloid, lanuginosine were isolated from the aerial parts of Ellipeiopsis cherrevensis (Annonaceae). Two known polyoxygenated cyclohexene derivatives, ferrudiol and zeylenol, and a new analog, ellipeiopsol D, were also isolated. The chalcone 2 exhibited cytotoxic activity against human small-cell lung-cancer (NCI-H187), epidermoid carcinoma (KB) and breast cancer (BC) cell lines with IC50 values of 1.40, 5.31 and 13.92 microg/mL, respectively. This compound also showed antimalarial activity against Plasmodium falciparum with an IC50 value of 7.1 microg/mL as well as antimicrobacterial activity against Mycobacterium tuberculosis with a MIC of 25 mg/mL.

Potential cancer chemopreventive constituents of the leaves of Macaranga triloba.

Activity-guided fractionation of the leaves of Macaranga triloba, using an in vitro bioassay based on the inhibition of cyclooxygenase-2, resulted in the isolation of a rotenoid, 4,5-dihydro-5'alpha-hydroxy-4'alpha-methoxy-6a,12a-dehydro-alpha-toxicarol (1), as well as 12 known compounds, (+)-clovan-2beta,9alpha-diol, ferulic acid, 3,7,3',4'-tetramethylquercetin, 3,7,3'-trimethylquercetin, 3,7-dimethylquercetin, abscisic acid, 1beta,6alpha-dihydroxy-4(15)-eudesmene, 3beta-hydroxy-24-ethylcholest-5-en-7-one, loliolide, scopoletin, taraxerol, and 3-epi-taraxerol. The structure of compound 1 was determined using spectroscopic methods. All isolates were evaluated for their potential to inhibit cyclooxygenases-1 and -2 by measuring PGE(2) production, and to induce quinone reductase in cultured Hepa 1c1c7 mouse hepatoma cells.

Prenylated flavonoids of the leaves of Macaranga conifera with inhibitory activity against cyclooxygenase-2.

Two prenylated flavonoid derivatives, 5-hydroxy-4'-methoxy-2",2"-dimethylpyrano-(7,8:6",5")flavanone (1) and 5,4'-dihydroxy-[2"-(1-hydroxy-1-methylethyl)dihydrofurano]-(7,8:5",4")flavanone (2), were isolated from an ethyl acetate-soluble extract of the leaves of Macaranga conifera using an in vitro activity-guided fractionation procedure based on the inhibition of cyclooxygenase-2. Also obtained were eight known compounds, 5,7-dihydroxy-4'-methoxy-8-(3-methylbut-2-enyl)flavanone (3), lonchocarpol A (4), sophoraflavanone B (5), 5,7-dihydroxy-4'-methoxy-8-(2-hydroxy-3-methylbut-3-enyl)flavanone (6), tomentosanol D (7), lupinifolinol (8), isolicoflavonol (9), and 20-epibryonolic acid (10). The structures of compounds 1 and 2 were determined using spectroscopic methods. All isolates were tested for their inhibitory effects against both cyclooxygenases-1 and -2, and selected compounds were evaluated in a mouse mammary organ culture assay.

Effects of nonsaponin fraction of red ginseng on learning deficits in aged rats.

Previously we reported that oral application of red ginseng significantly ameliorated learning deficits in aged rats and young rats with hippocampal lesions. In the present study, we investigated the effects of the nonsaponin fraction of red ginseng on learning deficits in aged rats in behavioral studies and those on long-term potentiation (LTP) in the hippocampal CA3 subfield in young rats in electrophysiological studies. In the behavioral studies, three groups of rats [aged rats with and without oral administration of the nonsaponin fraction of red ginseng and young rats] were tested with the three types of spatial-learning task [distance movement task (DMT), random-reward place search task (RRPST), and place-learning task (PLT)] in a circular open field. The results in the DMT and RRPST indicated that motivational and motor activity was not significantly different among the three groups of rats. However, performance of the aged rats without nonsaponin was significantly impaired in the PLT when compared with the young rats. Treatment with nonsaponin significantly ameliorated deficits in place-navigation learning in the aged rats in the PLT. In the electrophysiological studies, effects of nonsaponin on the LTP in the CA3 subfield of the hippocampal slices were investigated in vitro. Pretreatment with nonsaponin significantly augmented the increase in population spike amplitudes in the CA3 subfield after LTP induction. These results suggest that the nonsaponin fraction of red ginseng contains important substances to improve learning and memory in aged rats and that this amelioration by nonsaponin might be attributed partly to augmentation of LTP in the CA3 subfield.

A new arylnaphthalene lignan from Knema furfuracea.

A new arylnaphthalene lignan, named furfuracin, was isolated from the leaves of Knema furfuracea (Myristicaceae), whereas 7 known compounds including (+)-trans-1,2-dihydrodehydroguaiaretic acid, fragransin A(2), biochanin A, gingkolic acid, anarcardic acid, 2-hydroxy-6-(12-phenyldodecyl)-benzoic acid and 2-hydroxy-6-(12-phenyldodecen-8'Z-yl)-benzoic acid were obtained from its stems. The structure of the new lignan was established by analysis of spectroscopic data (UV, IR, MS and NMR).

Canarosine: a new guanidine alkaloid from Canavalia rosea with inhibitory activity on dopamine D1 receptors.

A new acyclic guanidine alkaloid, canarosine (1), together with five known compounds, beta-sitosterol (2), stigmasterol (3), daucosterol (4), epi-inositol 6-O-methyl ether (5), and rutin (6), were isolated from the aerial parts of Canavalia rosea. Their structures were established on the basis of their spectroscopic data. In the radioligand receptor binding assay, canarosine (1), at a concentration of 100 microg/ml, caused 91% inhibition of the dopamine D1 receptor binding with an IC50 value of 39.4 +/- 5.8 microM.

Inclusion effect and structural basis of cyclodextrins for increased extraction of medicinal alkaloids from natural medicines.

The enhancing effects of alpha-, beta-, and gamma-cyclodextrins (CyDs) on the aqueous extraction of ephedrine and berberine from the natural medicines were investigated in HPLC analysis, and the greatest effect was observed for beta- and gamma-CyDs. To clarify the structural basis of such an increased extraction effect with beta-CyD, possible interaction modes of (1R,2S)-ephedrine with alpha-, beta-, and gamma-CyDs were investigated using molecular dynamic simulations in an aqueous solution system. It was shown that the wrapping model of ephedrine by beta-CyD is the most compact and thus increases the solubility most effectively, compared with those by other CyDs. The same mode could be possible for the greatest effect of gamma-CyD on the extraction of berberine from natural medicines. This clearly shows that CyDs are useful additives for the effective extraction of bioactive alkaloids from natural medicines.

Effects of ellagic acid and 2-(2,3,6-trihydroxy-4-carboxyphenyl)ellagic acid on sorbitol accumulation in vitro and in vivo.

Caesalpinia ferrea MART. (Leguminosae) called as Juca is one of the medicinal plants in Brazil used for diabetes. From the fruits of this plant, ellagic acid (EA) and 2-(2,3,6-trihydroxy-4-carboxyphenyl)ellagic acid (TEA) have been recently isolated as aldose reductase (AR) inhibitors. In this study, we examined to prove the inhibitory activity against AR of EA and TEA in vitro, and EA in vivo by measurement of the accumulation of sorbitol, which is the product of glucose reduction catalyzed by AR. TEA was not examined in vivo because of its shortage of yield from the fruits. EA and TEA significantly and dose-dependently inhibited sorbitol accumulation in erythrocytes, lens and sciatic nerve under incubating with glucose in vitro. EA at a dose of 75 mg/kg/d showed the most potent inhibition of sorbitol accumulation in erythrocytes, lens and sciatic nerve at 50, 75 and 100 mg/kg/d in vivo. These results suggest that the inhibitory activity of EA against AR causes to inhibit sorbitol accumulation by in vitro and in vivo experiments. EA is distributed in fruits and vegetables, so that taking them might be able to relieve diabetic complications.

A new isoflavone glycoside from Ceiba pentandra (L.) Gaertner.

From the 80% EtOH extract of the bark of Ceiba pentandra (L.) Gaertner, a new isoflavone glycoside was isolated along with known isoflavones, vavain and vavain glucoside. The structure was elucidated by spectroscopic analysis as 5-hydroxy-7,4',5'-trimethoxyisoflavone 3'-O-alpha-L-arabinofuranosyl(1-->6)-beta-D-glucopyranoside.

Capillary electrophoresis for simultaneous determination of emodin, chrysophanol, and their 8-beta-D-glucosides.

The simultaneous separation and determination of the major anthraquinones, emodin, chrysophanol, and their glucosides, of Rumex japonicus HOUTT., and emodin and emodin glucoside, of Cassia tora L., Rhamnus purshiana DC., Polygonum multiflorum THUNB., and P. cuspidatum SIEB. et ZUCC., were achieved by cyclodextrin modified capillary zone electrophoresis. The running electrolyte used in this method was 0.005 M alpha-cyclodextrin in 0.03 M borate buffer (pH 10.5) containing 10% acetonitrile, with an applied voltage of 20 kV.

Cytotoxic prenylated xanthones and the unusual compounds anthraquinobenzophenones from Cratoxylum sumatranum.

Six new xanthones, cratoxyarborenones A-F (1-6), were isolated from the leaves, twigs, and/or stem bark of Cratoxylum sumatranum along with the known compound, vismione B (9), as active constituents by bioassay-directed fractionation using the KB human cancer cell line cytotoxicity assay. In addition, two novel anthraquinobenzophenones, cratoxyarborequinones A (7) and B (8), and two known compounds, 2,4,6-trihydroxybenzophenone 4-O-geranyl ether and delta-tocotrienol, were obtained as inactive constituents.