Use of in vitro assays to assess the potential antigenotoxic and cytotoxic effects of saffron (Crocus sativus L.).

Saffron is harvested from the dried, dark red stigmas of Crocus sativus L. flowers. It is used as a spice for flavoring and coloring food and as a perfume. It is often used for treating several diseases. We assessed the antimutagenic, comutagenic and cytotoxic effects of saffron and its main ingredients using the Ames/Salmonella test system, two well known mutagens (BP, 2AA), the in vitro colony formation assay and four different cultured human normal (CCD-18Lu) and malignant (HeLa, A-204 and HepG2) cells. When only using the TA98 strain in the Ames/Salmonella test system, saffron showed non-mutagenic, as well as non-antimutagenic activity against BP-induced mutagenicity, and demonstrated a dose-dependent co-mutagenic effect on 2-AA-induced mutagenicity. The saffron component responsible for this unusual comutagenic effect was safranal. In the in vitro colony formation test system, saffron displayed a dose-dependent inhibitory effect only against human malignant cells. All isolated carotenoid ingredients of saffron demonstrated cytotoxic activity against in vitro tumor cells. Saffron crocin derivatives possessed a stronger inhibitory effect on tumor cell colony formation. Overall, these results suggest that saffron itself, as well as its carotenoid components might be used as potential cancer chemopreventive agents.

Orizabins V-VIII, tetrasaccharide glycolipids from the Mexican scammony root (Ipomoea orizabensis).

An extensive investigation of the so-called jalapin resinoid obtained from roots of the Mexican scammony, Ipomoea orizabensis, using high field NMR spectroscopy led to the characterization of six glycosides, including the known scammonins I (1) and II (2) and four new tetrasaccharides of jalapinolic acid, orizabins V-VIII (3-6). All the isolates (1-6) were found to be weakly cytotoxic toward human oral epidermoid carcinoma (KB).

Novel labdane diterpenes from the insecticidal plant hyptis spicigera1

Seven new labdane diterpenes with insecticidal properties were isolated from the aerial parts of Hyptis spicigera. Their structures were established on the basis of spectral (MS, 1H NMR, and 13C NMR) and chemical evidences as: 19-acetoxy-2alpha,7alpha, 15-trihydroxylabda-8(17),(13Z)-diene (1); 15,19-diacetoxy-2alpha, 7alpha-dihydroxylabda-8(17),(13Z)-diene (2); 7alpha,15, 19-triacetoxy-2alpha-hydroxylabda-8(17),(13Z)-diene (3); 19-acetoxy-2alpha,7alpha-dihydroxylabda-8(17),(13Z)-dien-15-al (4); 19-acetoxy-7alpha,15-dihydroxylabda-8(17),(13Z)-dien-2-one (5); 19-acetoxy-2alpha,7alpha-dihydroxylabda-14, 15-dinorlabd-8(17)-en-13-one (6); and 2alpha,7alpha,15, 19-tetrahydroxy-ent-labda-8(17),(13Z)-diene (7). Absolute configurations were established by application of Mosher's method. Compound 2 significantly inhibited larval growth of the European corn borer.

Methyl 4-hydroxy-3-(3'-methyl-2'-butenyl)benzoate, major insecticidal principle from Piper guanacastensis.

The CHCl3-soluble extract of Piper guanacastensis (Piperaceae) was found to have noteworthy insecticidal activity to Aedes atropalpus mosquito larvae (LC50 80.5 micrograms/mL). Bioassay-guided fractionation afforded methyl 4-hydroxy-3-(3'-methyl-2'-butenyl)benzoate (1) as the major bioactive constituent (LC50 20.5 micrograms/mL). The separation of compound 1 from its transesterification artifact (2), ethyl 4-hydroxy-3-(3'-methyl-2'-butenyl)benzoate, was achieved by recycling reversed-phase HPLC. The flavonoids acacetin, chrysin, and pinostrobin were also isolated from the active fraction but did not display insecticidal properties.

Hepatotoxic pyrrolizidine alkaloids in the Mexican medicinal plant Packera candidissima (Asteraceae: Senecioneae).

A study of the hepatotoxic pyrrolizidine alkaloids (PAs) contained in Packera candidissima (Greene) Weber & Löve (Senecio candidissimus Greene), a Mexican medicinal plant used for the treatment of kidney ailments and noted for its antiseptic properties, is reported. Analysis by TLC and GC-MS have shown the presence in high levels of both PAs and their N-oxides in the root (0.76% dry weight) and the aerial parts (0.36% dry weight) of the plant material. GC-MS analysis showed the presence of senecionine, integerrimine, retrorsine, and usaramine in the aerial parts. The root was found to contain senkirkine as the major component. These results indicate that users of this herb are at high risk of poisoning, especially members of certain cultural groups in Northern Mexico and the Hispanic population in the southwestern United States. In addition, two sesquiterpenes, neoadenostylone and epineoadenostylone were identified from the neutral extracts of this plant material. The 6 alpha-angeloyloxy-9-oxo-delta 10(1)-furanoeremophilane is reported for the first time as a natural product.

Cytotoxic constituents from Hyptis verticillata.

A new cytotoxic (P-388 ED50 4 microgm/ml) arylnaphthalene lignan has been isolated from the Mexican medicinal plant Hyptis verticillata (Lamiaceae) and characterized as 5-methoxydehydropodophyllotoxin [1]. Eight additional lignans were also obtained by bioactivity-directed fractionation using the brine shrimp lethality test. Of these, the dehydro-beta-peltatin methyl ether 2 (P-388 ED50 1.8 microgm/ml) is reported for the first time as a natural product isolate. The other bioactive compounds were identified as dehydropodophyllotoxin [3], deoxydehydropodophyllotoxin [4]. (--)-yatein [5], 4'-demethyldeoxypodophyllotixin [6], isodeoxypodophyllotoxin [7], deoxypicropodophyllin [8], and beta-apopicropodophyllin [9]. Each of these compounds was evaluated against a panel of cell lines comprising a number of human cancer cell types [breast, colon, fibrosarcoma, lung, prostate, KB, and KB-VI (a multi-drug resistant cell line derived from KB)] and murine lymphocytic leukemia (P-388). Lignans 1-4 showed marginal cytotoxic activity against the human cell lines tested. In contrast, compounds 5-9 demonstrated a general nonspecific activity comparable to that of podophyllotoxin [12] (ED50 < 10-2 microgm/ml). In addition, the antimitotic potential of these compounds was determined in the astrocytoma (ASK) assay. Finally, the plant was also shown to contain the flavonoid sideritoflavone (KB ED50 1.6 microgm/ml) and the known pentacyclic triterpenoids ursolic, maslinic, 2 alpha-hydroxyursolic and oleanolic acids.

Screening for antimicrobial activity of crude drug extracts and pure natural products from Mexican medicinal plants.

Preliminary antimicrobial screening against Candida albicans and selected Gram-positive and Gram-negative bacteria of methanol extracts prepared from eight Mexican medicinal plants, noted for their antiseptic properties, was conducted. The significant activity exhibited for extracts of Ratibida latipalearis, Teloxys graveolens, Dodonaea viscosa, Hyptis albida, H. pectinata, H. Suaveolens and H. verticillata tends to support their traditional use as anti-infective agents. Only the extract of Hintonia latiflora was inactive. The antimicrobial activities of 44 pure natural compounds and two derivatives were determined. Of these, only 23 compounds were effective in inhibiting the growth of the tested organisms (MIC less than or equal to 100 micrograms/ml).

Allelopathic potential of compounds isolated fromIpomoea tricolor cav. (Convolvulaceae).

The allelopathic potential ofI. tricolor, used in traditional agriculture as a weed controller, has been demonstrated by measuring the inhibitory activity of aqueous lixiviates and organic extracts of the plant material on seedling growth ofAmaranthus leucocarpus andEchinochloa crusgalli. Bioactivity-guided fractionation of the most active organic extract led to the isolation of the allelopathic principles, which turned out to be a mixture of glycosides, having jalapinolic acid as the aglycone portion glycosidically linked in the 11 position to an oligosaccharide composed of glucose, rhamnose, and fucose, which also combines with the carboxyl group of the aglycone to form a macrocyclic ester.