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Antiulcerogenic activity of four extracts obtained from the bark wood of Quassia amara L. (Simaroubaceae).

Quassia amara L., a neotropical forest shrub of the Simaroubaceae family, is widely used in Caribbean folk medicine and in some northern states of Brazil for the treatment of gastric ulcers. This plant is a source of numerous compounds including both beta-carbonile and cantin-6 alkaloids as well as, primarily, the bitter compounds known as quassinoids. We analyzed the possible antiulcerogenic activities of four extracts of different polarities: 70% ethanol (70% EtOH), 100% EtOH, 100% dichloromethane (DCM), and 100% hexane (HEX) obtained from Quassia amara bark. All extracts, administered at doses of 5000 mg/kg orally and 1000 mg/kg intraperitoneally, caused neither toxicity or death. In the indomethacin/bethanechol-induced gastric ulcer, 70% EtOH, 100% EtOH, DCM and HEX extracts, 100 mg/kg, p.o., inhibited the gastric ulcer (22.5, 23.4, 50.5, 46.8%, respectively). 70% EtOH, 100% EtOH, DCM, and HEX extracts reduced the gastric injury induced by the hypothermic restraint-stress test in mice (70.7, 80, 60, 82.7%, respectively). In the pylorus ligature of the mouse stomach, following pre-treatment with a single intraduodenal administration of 100 mg/kg of each extract, only 70% EtOH did not change the biochemical parameters of gastric juice. 100% EtOH, DCM and HEX extracts presented decreased gastric juice content, increased pH values and decreased acid output. We also determined the antiulcerogenic activity on HCl-EtOH-induced gastric ulcers in mice at four doses (25, 50, 75, 100 mg/kg, p.o.), then evaluated the possible dose-dependent relation and calculated the ED50 values. Except for 70% EtOH at a dose of 25 mg/kg, the other extracts showed significantly activity (p<0.05). The free mucous amount in the gastric stomach content was also evaluated. All extracts showed significant increases (p<0.05) of free mucous. This effect was abolished when the animals were pre-treated with indomethacin. Prostaglandin synthesis was evaluated by the administration of HEX extracts by the oral route (100 mg/kg). Prostaglandin synthesis was significantly, increased by 52.3% (p<0.05), and this effect was abolished with prior administration of indomethacin. We concluded that Quassia amara is a probable source for a new drug to treat gastric ulcers, and the mechanism of its activity relates to cytoprotective factors, such as mucous and prostaglandins, but there is still the possibility that antisecretory activity is involved in its antiulcerogenic effect.

Animals↗

Indonesian medicinal plants. VIII. Chemical structures of three new triterpenoids, bruceajavanin A, dihydrobruceajavanin A, and bruceajavanin B, and a new alkaloidal glycoside, bruceacanthinoside, from the stems of Brucea javanica (Simaroubaceae).

Three new apotirucallane-type triterpenoids named bruceajavanin A (1) dihydrobruceajavanin A (2) and bruceajavanin B (3), and a novel beta-carboline alkaloidal glycoside named bruceacanthinoside (4) were isolated from the stems of Brucea javanica (Simaroubaceae), a traditional medicine used to treat malaria in the Bengkulu area, Sumatra, Indonesia. Their chemical structures have been elucidated on the bases of their chemical and physicochemical properties. Bruceajavanin A (1), dihydrobruceajavanin A (2) and bruceacanthinoside (4) were shown to inhibit growth of the cultured malarial parasite Plasmodium falciparum K1 of a chloroquine-resistant strain.

Animals↗

Potential anticancer agents vi. Constituents of Ailanthus excelsa (Simaroubaceae).

Ailanthione (1), glaucarubinone (2) and a mixture of glaucarubol 15-isovalerate (3) and 13,18-dehydroglaucarubol 15-isovalerate (4) were found to be the compounds responsible for the antitumor and cytotoxic activities of extracts of the root bark of Ailanthus excelsa (Simaroubaceae). The latter compound, 4, is new.

Antineoplastic Agents↗

Antiplasmodial activity of extracts and quassinoids isolated from seedlings of Ailanthus altissima (Simaroubaceae).

Extracts and isolated compounds from seedlings of Ailanthus altissima, were assessed for antiplasmodial activity in vitro. Two quassinoids, ailanthone and 6alpha-tigloyloxychaparrinone, isolated from the active extracts showed activity against both chloroquine-resistant and chloroquine-sensitive strains of Plasmodium falciparum in vitro. Only ailanthone demonstrated low toxicity against the Vero cell line (kidney cells from the African green monkey). This is the first report of the isolation and antiplasmodial activity of 6alpha-tigloyloxychaparrinone from this species.

Ailanthus↗

Potential anticancer agents IX. Isolation of a new simaroubolide, 6alpha-tigloyloxychaparrinone, from Ailanthus integrifolia ssp. calycina (Simaroubaceae).

Chaparrinone (1) and 6alpha-tigloyoxychaparrinone (2) were shown to be responsible for the antitumor and cytotoxic activities of the root bark of Ailanthus integrifolia ssp. calycina. The structure of the latter compound was established by analysis of spectral data. Compound 2 exhibited a more pronounced biological activity than chaparrinone (1) and demonstrates, for the first time, anticancer activity of a simaroubolide ester substituted at only the 6-position.

Animals↗

Phylogenetic relationships of Rutaceae: a cladistic analysis of the subfamilies using evidence from RBC and ATP sequence variation.

Sequence data for plastid rbcL and atpB from members of Anacardiaceae, Burseraceae, Cneoraceae, Meliaceae, Ptaeroxylaceae, Rutaceae, and Simaroubaceae were analyzed cladistically to evaluate the familial and subfamilial circumscriptions of Rutaceae. Taxa representing all subfamilies and tribes were sampled. The analysis shows that Rutaceae are paraphyletic, with Spathelia and Dictyoloma (Rutaceae), Harrisonia (Simaroubaceae), Cneorum (Cneoraceae), and Ptaeroxylon (Ptaeroxylaceae) forming a clade sister to all other Rutaceae. Circumscription of Rutaceae to include all of these taxa is recommended. This analysis indicates that Simaroubaceae and Meliaceae are the outgroups closest to Rutaceae. Correlation of the molecular phylogenies with biochemical data indicates that chemotaxonomic information is more reliable than fruit type as an indicator of familial and subfamilial circumscriptions. The subfamilial classification needs revision; none of the subfamilies of more than one genus is monophyletic.

Journal Article↗

Quassinoids from Eurycoma longifolia as plant growth inhibitors.

Seven quassinoids including a new 12-epi-11-dehydroklaineanone were isolated from the leaves of Eurycoma longifolia (Simaroubaceae) as plant growth inhibitors or related compounds. The strongest activity was found in 14,15beta-dihydroxyklaineanone.

Molecular Structure↗

Antiviral activity of simalikalactone D, a quassinoid from Quassia africana.

After removing lipophilic material, the ground root bark of Quassia africana Baill. (Simaroubaceae) was extracted with ethanol 95 %. Partitioning between chloroform, ethyl acetate and water yielded three crude extracts. Pronounced activities were shown by the chloroform and ethyl acetate crude extracts against Herpes simplex, Semliki forest, Coxsackie and Vesicular stomatitis viruses. By repeated column chromatography and preparative thin layer chromatography on silica gel, two quassinoids, i. e., quassin and simalikalactone D were isolated. Structures of the pure compounds were established primarily using NMR spectroscopy. Mass spectral information confirmed the assigned structures. Simalikalactone D was responsible, at least in part, for the high antiviral activity observed for the chloroform crude extract. Quassin showed no activity. For quassinoids the ester group at C-15 and the epoxymethano bridge between C-8 and C-13 appeared to be important structural features in order to exhibit a pronounced antiviral activity.

Antineoplastic Agents, Phytogenic↗

The isolation and structure of 13,18-dehydroglaucarubinone, a new antineoplastic quassinoid from Simarouba amara.

An investigation of the Guyana plant Simarouba amara Aubl. (Simaroubaceae) for antineoplastic quassinoids led to isolation and structural determination of the new quassinoids 2'-acetylglaucarubine (1a) and 13,18-dehydroglaucarubinone (2). The previously known 2'-acetylglaucarubinone (3a) and glaucarubinone (3b) were also obtained. The new quassinoid 2 was found significantly to inhibit growth of the murine lymphocytic leukemia P388.

Antineoplastic Agents, Phytogenic↗

Can ethnopharmacology contribute to the development of antimalarial agents?

The resistance of Plasmodium falciparum, the cause of tertian malaria, to synthetic antimalarials, together with the resistance of the vector mosquitoes to insecticides, has resulted in a resurgence in the use of quinine and a search for new antimalarial agents. In recent years, artemisinin, isolated from Artemisia annua which is used in Chinese traditional medicine for the treatment of malaria, has proved to be effective in the treatment of cerebral malaria due to chloroquine-resistant strains of P. falciparum. The development of in vitro tests utilising P. falciparum obtained from malaria patients means that it is possible to use bioassay guided fractionation of active extracts in order to isolate active principles. A number of laboratories throughout the world are currently investigating plants used in traditional medicine for their active constituents. Some of their results will be described and in particular two aspects of our investigations with species of Simaroubaceae and Menispermaceae will be discussed. There is every possibility that such approaches which use leads from Ethnopharmacology will result in the development of new antimalarial agents. It is vitally important to those populations relying on traditional medicines for the treatment of malaria that the safety and efficacy of such medicines be established, their active principles determined and that reproducible dosage forms be prepared and made available for use.

Animals↗

Antimalarial activity of cedronin.

Cedronin was isolated from Simaba cedron Planchon (Simaroubaceae), a species popularly believed in South America to have antimalarial properties. It was examined for in vitro and in vivo antimalarial activities and for cytotoxicity against KB cells. Experimental results showed that cedronin was active against chloroquine-sensitive and resistant strain, with an IC50 of 0.25 micrograms/ml (0.65 mumol/ml). It was also found to be active in vivo against Plasmodium vinkei with an IC50 of 1.8 mg/kg (4.7 nM/kg) in the classic 4-day test. Cedronin belongs to the small group of quassinoids with a C19 basic skeleton and shows a rather low cytotoxicity against KB cells (IC50 = 4 micrograms/ml, 10.4 microM) as compared with C20 biologically active quassinoids; however its toxic/therapeutic ratio (10/1.8) remains lower than chloroquine (10/0.5).

Animals↗

Antimalarial and cytotoxic potential of four quassinoids from Hannoa chlorantha and Hannoa klaineana, and their structure-activity relationships.

Hannoa chlorantha and Hannoa klaineana (Simaroubaceae) are used in traditional medicine of Central African countries against fevers and malaria. Four stem bark extracts from H. klaineana and four quassinoids from H. chlorantha were examined in vitro against Plasmodium falciparum NF 54. The extracts displayed good activities, while the quassinoids were highly active, with IC50 values well below 1 microgram ml-1, those of chaparrinone and 15-desacetylundulatone being much lower than 0.1 microgram ml-1 (0.037 and 0.047 microgram ml-1, respectively). Chaparrinone is five times more active than 14-hydroxychaparrinone against P. falciparum, indicating that the hydroxyl function at C-14 is unfavourable for antiplasmodial activity. As 14-hydroxychaparrinone has a seven-times higher cytotoxic activity against P-388 cells than chaparrinone, the latter compound has the better antiplasmodial therapeutic index. All four quassinoids were evaluated in vivo in a standard 4-day test as well. 15-Desacetylundulatone was proven to be the most active compound, almost totally suppressing the parasitaemias of OF1 mice for at least 7 days, while both chaparrinone and 14-hydroxychaparrinone were active for at least 4 days. Quassinoids have ED50 values much lower than 50 mg kg-1 body weight day-1 and none of them caused obvious side effects. The keto function at C-2 in 15-desacetylundulatone is apparently of crucial importance for its high activity. 6-alpha-Tigloyloxyglaucarubol was not active at all. Chaparrinone is considered the most interesting of the investigated quassinoids and its in-vivo antimalarial potential will be examined further.

Animals↗

In vitro anti-tumor promoting and anti-parasitic activities of the quassinoids from Eurycoma longifolia, a medicinal plant in Southeast Asia.

Some quassinoids (1-6) isolated previously as plant growth inhibitors from the leaves of Eurycoma longifolia Jack. (Simaroubaceae) were subjected to in vitro tests on anti-tumor promoting, antischistosomal and plasmodicidal activities. The most active compound for inhibition of tumor promoter-induced Epstein-Barr virus activation (anti-tumor promotion) was 14,15beta-dihydroxyklaineanone (5, IC(50) = 5 microM). Longilactone (1) gave significant antischistosomal effect at a concentration of 200 microg/ml. 11-Dehydroklaineanone (3) and 15beta-O-acetyl-14-hydroxyklaineanone (6) showed potent plasmodicidal activity (IC(50) = 2 microg/ml). Thus it was suggested that E. longifolia possesses high medicinal values due to the occurrence of a variety of quassinoids.

Animals↗

Antiplasmodial activity of selected Sudanese medicinal plants with emphasis on Maytenus senegalensis (Lam.) Exell.

The antiplasmodial activity of plant extracts related to four families was tested on chloroquine sensitive strain 3D7 and chloroquine resistant strain Dd2 of Plasmodium falciparum. The methanolic extract of Harrisonia abyssinica (Simaroubaceae) inhibited Dd2 with IC50 value of 4.7 microg/ml, while in 3D7, the IC50 value was 10 microg/ml. Most of the plants from the family Meliaceae showed highly potent antiplasmodial activity against the two tested strains. Khaya senegalensis, Azadirachta indica and Trichilia emetica showed IC50 values less than 5 microg/ml. The methanolic extract of Annona squamosa (Annonaceae) leaves showed high antiplasmodial activity with IC50 values of 2 and 30 microg/ml on 3D7 and Dd2, respectively. While stem bark showed moderate activity with IC50 values of 8.5 and 120 microg/ml on Dd2. Maytenus senegalensis (Celastraceae) possessed IC50 values of 3.9 on 3D7, 10 microg/ml on Dd2 and had no effect on lymphocyte proliferation even at the highest tested concentration; the IC50 was greater than 100 microg/ml. Liquid-liquid separation of the methanolic extract of M. senegalensis revealed that the dichloromethane extract possessed an IC50 value of only 2.1 microg/ml. Column fractionation of dichloromethane extract gave four fractions and fraction two showed an IC50 value of 0.5 microg/ml. Preliminary phytochemical analysis of dichloromethane fraction revealed terpenoids and traces of phenolic principles but no alkaloid, tannins or flavonoids were detected.

Animals↗

In vivo antimalarial activities of Quassia amara and Quassia undulata plant extracts in mice.

Extracts obtained from two Nigerian Simaroubaceae plants, Quassia amara L. and Quassia undulata (Giull and Perr) D. Dietr were screened for antimalarial properties using a total of six extracts. The plant extracts showed significant antimalarial activities in the 4 day suppressive in vivo antimalarial assay in mice inoculated with red blood cells parasitized with Plasmodium berghei berghei. Plant extracts were studied at 100 mg and 200 mg per kg body weight mouse per day, respectively. At a concentration of 100 mg/kg of mouse, Q. amara leaf hexane extract had the highest suppressive activity with a parasite density of 0.16 +/- 0.001%. Q. amara leaf methanol extract had an outstanding activity; of 0.05 +/- 0.03% at 200 mg/kg. Chloroquine (10 mg/kg, positive control) had a suppressive activity of 0.34 +/- 0.02 in the same assay on day 4.

Animals↗

The antineoplastic quassinoids of Simaba cuspidata spruce and Ailanthus grandis Prain.

The South American Simaba cuspidata Spruce and North Indian Ailanthus grandis Prain were investigated as sources of potentially useful antineoplastic agents. Both of these Simaroubaceae plant species were found to produce 6 alpha-tigloyloxychaparrinone (4a) and the new quassinoid 6 alpha-tigloyloxychaparrin (3b). The latter structure was determined by interpretation of spectral data and oxidation to 6 alpha-tigloyloxychaparrinone (4a). While both glycol 3b and alpha-ketol 4a were found to significantly inhibit growth of the murine P388 lymphocytic leukemia cell line, only the alpha-ketol (4a) inhibited growth of the corresponding in vivo system.

Animals↗

Plant anticancer agents. XXIV. Alkaloid constituents of Simaba multiflora.

Two new cytotoxic canthin-6-ones, 10-methoxycanthin-6-one (1) and 10-hydroxycanthin-6-one (2) were isolated from the wood of Simaba multiflora (Simaroubaceae). Three canthin-2,6-dione (3), 3-methoxycanthin-2,6-dione (4) and canthin-2,6-dione (5), as well as scopoletin (7) and the novel coumarino-lignan cleomiscosin A (6) were also obtained.

Acetylation↗