Identification of the main volatile compounds in the leaf and flower of <Emphasis Type="Italic">Tithonia diversifolia</Emphasis> (Hemsl) Gray

The composition of the essential oils of the leaves and flowers of Tithonia diversifolia (Hemsl) A. Gray, Mexican sunflower, are reported. The oils were obtained by hydrodistillation in an all-glass Clevenger-type apparatus and analyzed by GC–MS. The leaf oil was comprised of an abundance of α-pinene (32.9%), β-caryophyllene (20.8%), germacrene D (12.6%), β-pinene (10.9%) and 1, 8-cineole (9.1%). Germacrene D (20.3%), β-caryophyllene (20.1%) and bicyclogermacrene (8.0%) characterized the oil of the flower. A number of aliphatic fatty acids and a diterpenoid compound, sandaracopimaradiene, that were present in the flower, could not be detected in the leaf oil.     

Chemical composition and antibacterial activity of essential oils of <Emphasis Type="Italic">Eugenia</Emphasis> species

The essential oils of the leaves of Eugenia brasiliensis, Eugenia beaurepaireana, and Eugenia umbelliflora were analyzed by GC–MS. The major compounds found in the oil of E. brasiliensis were spathulenol (12.6%) and τ-cadinol (8.7%), of E. beaurepaireana were β-caryophyllene (8.0%) and bicyclogermacrene (7.2%), and of E. umbelliflora were viridiflorol (17.7%) and β-pinene (13.2%). These oils were assayed to determine their antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. All of the oils analyzed showed antibacterial activity, ranging from moderate to strong, which was most accentuated for the E. umbelliflora and E. brasiliensis oils, which strongly inhibited the growth of S. aureus giving values of MIC = 119.2 and 156.2 μg/mL, respectively.     

Composition of the essential oil from the root of <Emphasis Type="Italic">Artemisia annua</Emphasis>

Upon hydrodistillation, dried roots of Artemisia annua L. cultivar Jwarharti gave a pleasantly fragrant essential oil with a yield of 0.25%. GC and GC–MS analyses of the oil enabled the identification of 52 components representing 83.2% of the oil. The oil was rich in sesquiterpenes and oxygenated sesquiterpenes and had cis-arteannuic alcohol (25.9%), (E)-β-farnesene (6.7%), β-maaliene (6.3%), β-caryophyllene (5.5%), caryophyllene oxide (4.4%) and 2-phenylbenzaldehyde (3.5%) as its major components. The oil was found to possess considerable fumigant activity and ability to repel adult Tribolium castaneum beetles.     

<Emphasis Type="Italic">Perilla frutescens</Emphasis> var. <Emphasis Type="Italic">frutescens</Emphasis> in northern Laos

Twenty-eight samples of mericarps of Perilla frutescens var. frutescens were collected through fieldwork performed in Phongsali and Xieng Khouang provinces in northern Laos. No perilla samples were collected from Savannakhet province in the south although more than 20 sites were investigated. Perilla plants are mostly grown mixed with dry-paddy rice by slash-and-burn cultivation in Laos. The most popular local name for perilla mericarps in the area was “Ma Nga Chan”. Weight of 1,000 grains and hardness of the mericarps were measured, and all mericarps were found to be large (weight of 1,000 grains around 2 g) and soft (limit load weight under 300 g), which were preferred for culinary use in Laos. The composition of the essential oils obtained from the herbaceous plants raised from the mericarps was divided into five types, perillaketone, elemicine plus myristicine, shisofuran, piperitenon, and myristicine, and GC–MS analysis of these Laotian perilla samples showed that they were similar to those of corresponding types of known Japanese perilla strains. One of the shisofuran-type perilla contained large amounts of putative α-naginatene, which is likely to be an intermediate of the biosynthesis of naginataketone. The farmers' indifference to the oil type of the leaf seems to leave Laotian perilla as a good genetic resource for studies of the biosynthesis of oil compounds.     

Metabolism and pharmacokinetics in rats of ganoderiol F,a highly cytotoxic and antitumor triterpene from <Emphasis Type="Italic">Ganoderma lucidum</Emphasis>

The metabolism of ganoderiol F (GF), a cytotoxic and antitumor triterpene from Ganoderma lucidum, by intestinal bacteria and its pharmacokinetics in rats were investigated by using liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). GF was converted to ganodermatriol by anaerobic incubation with bacterial mixtures from rats and humans. This metabolite was detected in rat feces, but not in plasma and urine, after oral administration of GF. The fate of GF after oral (p.o.) and intravenous (i.v.) administration to rats was examined in pharmacokinetics studies. Plasma samples pretreated by solid-phase extraction were quantified by HPLC/MS/MS over a GF concentration range of 1.25–100 ng/ml (S/N = 5). The intra- and interday precision (CV%) was below 8% and accuracy was within the range of 95.9–103.6% for all samples. The range of recovery ratios was 89.2–98.2%. After the administration of GF at 0.5 mg/kg i.v., the plasma concentrations of GF quickly declined and the elimination half-life values (t _1/2α and t _1/2β) were about 2.4 and 34.8 min. On the other hand, the elimination half-life values (t _1/2α) after p.o. administration of GF at doses of 20 and 50 mg/kg were 14.4 and 143.3 min for the former, and 18.6 and 114.6 min for the latter. The AUC_0–t value was 11.17 (ng/ml) h at a GF dose of 0.5 mg/kg i.v., but 49.4 and 111.6 (ng/ml) h at GF doses of 20 and 50 mg/kg p.o., respectively, indicating that the AUC_0–t value is proportional to the administered oral doses. The estimated absolute bioavailability of GF in rats was F = 0.105.     

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.     

Antioxidative activity of the flower of <Emphasis Type="Italic">Torenia fournieri</Emphasis>

The edible flower of Torenia fournieri Linden ex E. Fourn was found to possess potent antioxidative activity in a rat brain homogenate model. Bioassay-guided isolation of the active compounds from a CH₂Cl₂–MeOH (1:1) extract led to the isolation of acteoside (1), luteolin-7-O-β-glucoside (2), apigenin-7-O-α-rhamnosyl-(1→6)-β-glucoside (3), and apigetrin (4).     

Triterpenoic acids of Prunella vulgaris var. lilacina and their cytotoxic activities In Vitro

The column chromatographic separation of the MeOH extract from the aerial parts of Prunella vulgaris var. lilacina Nakai led to the isolation of fifteen triterpenoic acids (2–6, 9–13, 16–20), four flavonoids (14, 21–23), four phenolics (7, 8, 15, 24), and a diterpene (1). Their structures were determined by spectroscopic methods to be trans-phytol (1), oleanic acid (2) ursolic acid (3), 2α,3α,19α-trihydroxyurs-12en-28oic acid (4), 2α,3α-dihydroxyurs-12en-28oic acid (5), maslinic acid (6), caffeic acid (7), phydroxy cinnamic acid (8), 2α,3α,19α,23-tetrahydroxyurs-12en-28oic acid (9), 2α,3α,23-trihydroxyurs-12en-28oic acid (10), 2α,3β-dihydroxyurs-12en-28oic acid (11), 2α,3β,24-trihydroxyolea-12en-28oic acid (12), (12R, 13S)-2α,3α,24,trihydroxy-12,13-cyclo-taraxer-14-en-28oic acid (13), quercertin 3-O-β-D-glucopyranoside (14), rosmarinic acid (15), 2α,3α,24-trihydroxyurs-12,20(30)-dien-28oic acid (16), 2α,3α,24-trihydroxyolea-12en-28oic acid (17), 2α,3β,19α,24-tetrahydroxyurs-12en-28oic acid 28-O-Dglucopyranoside (18), 2α,3α,19α,24-tetrahydroxyurs-12en-28oic acid 28-O-D-glucopyranoside (19), prunvuloside A (20), kaempferol 3-O-α-L-rhamnopyranosyl(1→6)-β-D-glucopranoside (21), kaempferol 3-O-β-D-glucopyranoside (22), quercertin 3-O-α-L-rhamnopyranosyl(1→6)-β-D-glucopyranoside (23), and 2-hydroxy-3-(3’,4’-dihydroxyphenly)propanoic acid (24). Compounds 1, 8–12, 17, 21, 23, and 24 were isolated from this plant source for the first time. The isolated compounds were evaluated for their cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT15 cells in vitro using the sulforhodamin B bioassay (SRB) method. Compound 3 exhibited moderate cytotoxic activity against A549, SK-OV-3, SK-MEL-2, and HCT15 cells, with ED₅₀ values of 3.71, 3.65, 13.62, and 5.44 μM, respectively.     

Triacylglycerols of the lipid fraction from fruits of two <Emphasis Type="Italic">Echinacea</Emphasis> species

Fatty oils extracted from the fruits of Echinacea purpurea and E. pallida species have been analyzed. The extracts represent oily and readily mobile light yellow liquids. Fruits of E. purpurea contain 33.6% fatty oil; of E. pallida, 23.2%. NMR spectroscopy analyses of fatty oils from fruits of the two Echinacea species show that these substances belong to liquid plant oils such as linoleic acid, which is confirmed by the measured numerical indices. Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 43, No. 3, pp. 32 – 34, March, 2009.     

Dimethylamino-functionalised and <Emphasis Type="Italic">N</Emphasis>-heteroaryl-substituted titanocene anticancer drugs: synthesis and cytotoxicity studies

Summary From the carbolithiation of 6-N,N-dimethylamino fulvene (3a) and different lithiated N-heterocyclic compounds (N,N-dimethylaminomethylpyrrole, 1-methylimidazole and 2,4-[bis(N′,N′-dimethylaminomethyl)]-N-methyl pyrrole), the corresponding lithium cyclopentadienide intermediate (4a–c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl₄ resulting in dimethylamino-functionalised titanocenes 5a–c. When these titanocenes were tested against LLC-PK cells, the IC₅₀ values obtained were of 13, and 63 μM for titanocenes 5b and 5c, respectively. The most cytotoxic titanocene in this paper (5a) with an IC₅₀ value of 6.8 μM is found to be almost as cytotoxic as cis-platin, which showed an IC₅₀ value of 3.3 μM, when tested on the epithelial pig kidney LLC-PK cell line, and titanocene 5c is approximately 400 times better than titanocene dichloride itself.     

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.     

Anti-oxidative and inhibitory activities on nitric oxide (NO) and prostaglandin E<Subscript>2</Subscript> (COX-2) production of flavonoids from seeds of <Emphasis Type="Italic">Prunus tomentosa</Emphasis> Thunberg

Chemical investigation of the 80% Me₂CO extract from the seeds of Prunus tomentosa led to the isolation and identification of six flavonoids: kaempferol (1), kaempferol 3-O-α-L-rhamnopyranoside (2; afzelin), kaempferol 3-O-β-D-(6-acetyl)-glucopyranosyl(1→4)-α-L-rhamnopyranoside (3; multiflorin A), kaempferol 3-O-β-D-glucopyranosyl(1→4)-α-L-rhamnopyranoside (4; multiflorin B), quercetin 3-O-α-L-rhamnopyranoside (5; quercitrin), and quercetin 3-O-β-D-glucopyranosyl (1→4)-α-L-rhamnopyranoside (6; multinoside A). Anti-oxidative and inhibitory activities on nitric oxide (NO) and prostaglandin E₂ production in interferon-γ (INF-γ) and lipopolysaccharide (LPS)-activated RAW 264.7 cells in vitro (COX-2) of the isolated compounds were evaluated. Compounds 1, 5, and 6 exhibited potent anti-oxidative activity in the DPPH radical scavenging assay with IC₅₀ values of 57.2, 59.4, and 54.3 μg/mL respectively. The positive control, ascorbic acid, had an IC₅₀ of 55.5 μg/mL. Compounds 1, 5, and 6 also reduced COX-2 levels in a dose dependent manner with IC₅₀ values of 10.2, 8.7, and 9.6 μg/mL respectively, with the positive control, indomethacin, having an IC₅₀ of 5.1 μg/mL. All six compounds inhibited NO production in a dose dependent manner with IC₅₀ values of 35.1, 42.8, 40.0, 44.8, 43.7, and 43.9 μg/mL respectively, while the positive control, L-NMMA, had an IC₅₀ of 42.1 μg/mL.     

Stilbenes and oligostilbenes from leaf and stem of <Emphasis Type="Italic">Vitis amurensis</Emphasis> and their cytotoxic activity

Chromatographic separation of the EtOAc fraction from the leaf and stem of Vitis amurensis led to the isolation of six oligostilbenoids (i.e., r-2-viniferin (1), trans-amurensin B (2), trans-ɛ-viniferin (3), gnetin H (4), amurensin G (5), (+)-ampelopsin A (8)) and four stilbenoids (i.e., trans-resveratrol (6), (+)-ampelopsin F (7), piceatannol (9), and trans-piceid (10)). The structures have been identified on the basis of spectroscopic evidence and physicochemical properties. The isolates were investigated for cytotoxic activity against three cancer cell lines in vitro using the MTT assay method. Amurensin G (5) and trans-resveratrol (6) showed significant cytotoxic activity against L1210, K562 and HTC116 cancer cell lines with IC₅₀ values ranging from 15.7 ± 2.1 to 30.9 ± 1.8 μM. (+)-Ampelopsin A (8) and trans-piceid (10) exhibited considerable cytotoxic activity against L1210 (IC₅₀ values of 30.6 ± 4.1 and 28.7 ± 2.81 μM, respectively) and K562 (IC₅₀ values of 38.6 ± 0.82 and 24.6 ± 0.76 μM, respectively). Gnetin H (4) showed only weak cytotoxic activity against L1210 with an IC₅₀ value of 40.1 ± 4.23 μM. On the other hand, r-2-viniverin (1), trans-amurensin B (2), trans-ɛ-viniferin (3), (+)-ampelopsin F (7), and piceatannol (9) exhibited no activity on three cancer cell lines.     

A new triterpenoid from <Emphasis Type="Italic">Panax ginseng</Emphasis> exhibits cytotoxicity through p53 and the caspase signaling pathway in the HepG2 cell line

A new triterpenoid, 20(R),22(ξ),24(S)-dammar-25(26)-ene-3β,6α,12β,20,22,24-hexanol (1), and three known triterpenoids, β-D-glucopyranoside,(3β,12β)-12,20-dihydroxydammar-24-en-3-yl,6-acetate (2), 20(R)-ginsenoside Rg₃ (3), and 20(R)-ginsenoside Rh₂ (4), were isolated from the leaves of Panax ginseng. Their structures were determined by chemical analysis and spectral methods (IR, 1D and 2D NMR, HR-ESI-MS). Compounds 1–4 were exhibited various degrees of cytotoxicity in the human hepatoma cell line, HepG2. Compound 1 had the highest cytotoxic potency, with an IC₅₀ value of 20.1 μM, by stimulating p53-mediated cell cycle arrest at the G1 to S phase transition, leading to apoptosis via activation of the caspase signaling pathway.     

Neolignans from North American Magnolia Species with Cyclooxygenase 2 Inhibitory Activity

Objectives:  Based upon reported ethnomedicinal use by Native Americans, extracts and pure isolates from leaves and seeds of Magnolia grandiflora, M. virginiana, M. acuminata and M. macrophylla, all native to the Southeastern United States, were investigated for their anti-inflammatory potential against cyclooxygenase 2 (COX-2). Material and methods:  The extracts and pure compounds from Magnolia species were tested for their production of prostaglandin E₂ (PGE₂) using a mouse macrophage (RAW 264.7) assay where cells were stimulated by lipopolysaccharide. Results:  Leaf extracts were moderately active (44–58% inhibition at 50 μg/ml) whereas seed extracts showed significant activity of 54–88% inhibition, respectively. In the seed extract of M. grandiflora, honokiol, magnolol and 4’-O-methylhonokiol strongly inhibited COX-2 (IC₅₀: 1.2–2.0 μg/ml), 3-O-methylmagnolol was moderately active while a new compound was inactive towards COX-2. The neolignans were not cytotoxic to macrophages (RAW 264.7) and kidney fibroblast (VERO) cells in vitro. Conclusions:  The results indicate that the reported ethnomedicinal use of the investigated Magnolia species is in agreement with anti-inflammatory activity of their respective compounds. Received 8 December 2007; accepted 16 January 2009     

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.     

Chemical composition and cytotoxic, mutagenic and genotoxic activities of the essential oil from Piper gaudichaudianum Kunth leaves

We have investigated the chemical composition of Piper gaudichaudianum essential oil, as well as its cytotoxic, mutagenic and genotoxic effects in V79 cells. The chemical analyses showed that the major compounds are (E)-nerolidol (22.4%), α-humulene (16.5%), (E)-caryophyllene (8.9%) and bicyclogermacrene (7.4%). Dose-dependent cytotoxic effects were observed in V79 cells treated with essential oil by using clonal survival, 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide reduction assay (MTT) and trypan blue exclusion assay (TB), and a significant decrease in survival was observed at concentrations of 0.5 μg/mL and higher. The P. gaudichaudianum essential oil treatment caused DNA strand breaks in V79 cells at concentrations up to 2 μg/mL, as detected by the alkaline comet assay, but did not induce double-strand breaks, as verified by neutral comet assay. It induced a significant increase in the frequency of micronucleated cells at 4, 6 and 10 μg/mL. Moreover, P. gaudichaudianum essential oil significantly increased lipid peroxidation at doses of 0.5 μg/mL and higher, suggesting that the observed oxidant potential can be responsible, at least in part, for its cytotoxic and genotoxic effects.     

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.     

Hypoglycaemic effect of mollic acid glucoside,a 1α-hydroxycycloartenoid saponin extractive from <Emphasis Type="Italic">Combretum molle</Emphasis> R. Br. ex G. Don (Combretaceae) leaf,in rodents

In this study, we investigated the hypoglycaemic and antidiabetic properties of mollic acid glucoside (MAG), a 1α-hydroxycycloartenoid extractive from Combretum molle leaf, in rodents. Stepwise, escalated doses of MAG (5–80 mg/kg p.o.) produced dose-dependent and significant (P < 0.05–0.01) hypoglycaemic and antidiabetic effects in normal (normoglycaemic) and streptozotocin-treated diabetic rats. Experimental evidence obtained from this laboratory animal study indicates that MAG, an extractive from C. molle leaf, possesses hypoglycaemic and antidiabetic properties. These findings lend pharmacological credence to the folkloric, ethnomedical uses of the plant’s leaf in the management and/or control of diabetes mellitus in some rural communities of southern Africa.     

In vitro anti-plasmodial and in vivo anti-malarial activity of some plants traditionally used for the treatment of malaria by the Meru community in Kenya

Extracts of seven medicinal plant species used for treatment of malaria in traditional/cultural health systems of the Ameru people in Kenya were tested in vitro and in vivo against Plasmodium falciparum (D6 and W2 strains) and P. berghei, respectively. Of the plants tested, 28.57% were highly active (IC₅₀ <10 μg/ml) and 42.86% moderately active (IC₅₀ 10–50 μg/ml), while 28.57% had weak activity of 50–125 μg/ml in vitro. The water and methanol extracts of Boscia salicifolia Oliv. and Artemisia afra Jacq. (ex-Willd.) were the most active against both the chloroquine (CQ)-sensitive (D6) and the CQ-resistant (W2) P. falciparum strains. Artemisia afra and Rhus natalensis Bernh. (ex-Krauss) exhibited the highest parasite clearance and chemo-suppression (>70%) in vivo (in mice). The plants with high in vitro anti-plasmodial (low IC₅₀ values) and high anti-malarial activity (high chemo-suppression) in vivo are potential sources of novel anti-malarial drugs.