Antiplasmodial Compounds from Leaves of Dodonaea angustifolia.

BACKGROUND: Dodonaea angustifolia is used in Ethiopian traditional medicine to treat malaria. The objective of this work was to conduct bioassay guided fractionation of the leaves of D. angustifolia using Plasmodium berghei infected mice. METHOD: The antiplasmodial activity of the extracts and pure compounds was evaluated using the standard Peter's four-day suppressive method. The structures of isolated compounds were elucidated using chemi-cal and spectroscopic methods. RESULTS: In this study, the ethyl acetate soluble portion of the 80% aqueous MeOH extract of the leaves significantly suppressed parasitaemia in Plasmodium berghei infected mice (80.28% at 150 mg/kg). Three active compounds which exhibited significant percent suppression of parasitaemia by 81% at 40 mg/kg, 80% at 50 mg/kg and 70% at 40 mg/kg, respectively were identified. These are the flavanone pinocembrin (1), the flavanol santin (2) and the clerodane diterpene 2-hydroxy-15,16-epoxyceloda-3,13(16),14-trien-18-oic acid (3). Under similar conditions, chloroquine suppressed parasitaemia by 100% at 25 mg/kg. Chemical study of the ethanol extract of the leaves yielded 5,7,4'-trihydroxy-3,6-dimethoxyflavone (4), ent-16-hydroxy-labdan-3α,8ß-dihydroxy,13(14)-en-15,16-olide (5) and 5,6,7-trihydroxy-3,4'-dimethoxyflavone (6). Compound 6 has not been reported before as a natural product. CONCLUSION: From the leaves of D. angustifolia, three compounds with significant antiplasmodial activi-ties were isolated and characterized, with pinocembrin as the most active compound.

Antiplasmodial quinones from the rhizomes of Kniphofia foliosa.

Extracts of the rhizomes of Kniphofia foliosa exhibited antiplasmodial activities against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum with IC50 values of 3-5 microg/mL. A phenyloxanthrone, named 10-acetonylknipholone cyclooxanthrone (1) and an anthraquinone-anthrone dimer, chryslandicin 10-methyl ether (2), were isolated from the rhizomes, along with known quinones, including the rare phenylanthraquinone dimers, joziknipholones A and B. The structures of these compounds were determined based on spectroscopic data. This is the second report on the occurrence of the dimeric phenylanthraquinones in nature. In an in vitro antiplasmodial assay of the isolated compounds, activity was observed for phenylanthraquinones, anthraquinone-anthrone dimers and dimeric phenylanthraquinones, with joziknipholone A being the most active. The new compound, 10-acetonylknipholone cyclooxanthrone, also showed anti-plasmodial activity. In an in vivo assay, knipholone anthrone displayed marginal antimalarial activity.

Characterization of Constituents and Anthelmintic Properties of Hagenia abyssinica.

The dried female flowers of Hagenia abyssinica (Bruce) J. F. Gmel. (Rosaceae) are traditionally used as an anthelmintic remedy in Ethiopia and formerly were incorporated into the European Pharmacopoeia. One-, two- and tricyclic phloroglucinol derivatives (kosins) were suggested to be the active principles. However, polar constituents may also contribute to the activity. Therefore, we investigated for the first time the polar constituents. We isolated typical Rosaceae constituents such as quercetin 3-O-ß-glucuronide, quercetin 3-O-ß-glucoside and rutin. Polar kosin glycosides or derivatives could not be detected.The anthelmintic activity of fractions of different polarity were tested against the blood fluke Schistosoma mansoni, the liver flukes Clonorchis sinensis and Fasciola hepatica and the intestinal fluke Echinostoma caproni. The anthelmintic activity decreased with increasing polarity of the tested fractions. ESI-MS investigations indicated the predominant occurrence of kosins in the active fractions.Using the anthelmintic active extracts of Hagenia abyssinica we developed a simple, inexpensive bioassay against the non-parasitic nematode Caenorhabditis elegans, which can be used as an initial screening procedure for anthelmintic properties of crude extracts of plants or fungi. The anthelmintic activity of test extracts against the model organism was determined in a microtiter plate assay by enumeration of living and dead nematodes under a microscope.

Comparative antioxidant, prooxidant and cytotoxic activity of sigmoidin A and eriodictyol.

Sigmoidin A (SGN) is a prenylated flavanone derivative of eriodictyol (ERD) with reported moderate antioxidant, antimicrobial and anti-inflammatory activity. Since ERD and other structurally similar antioxidant phenolic compounds have been shown to induce prooxidative macromolecular damage and cytotoxicity in cancer cells, the comparative IN VITRO effects of these structural analogues on cancer cell viability and Cu(II)-dependent DNA damage were studied. In the presence of Cu(II) ions, both SGN and ERD (7.4-236 microM) caused comparable concentration-dependent pBR322 plasmid DNA strand scission. The DNA damage induced by SGN and ERD could be abolished by ROS scavengers, glutathione (GSH) and catalase as well as EDTA and a specific Cu(I) chelator neocuproine. Both ERD and SGN readily reduce Cu(II) to Cu(I) suggesting a prooxidative mechanism of DNA damage. In a cell free system, ERD and SGN did also show comparable radical scavenging activity. SGN was, however, by an order of magnitude more cytotoxic to cancer cells than ERD and this effect was significantly attenuated by GSH suggesting a prooxidative mechanism of cell death. A depletion of intracellular GSH level by SGN in cancer cells is also demonstrated.

Four lignans from Commiphora erlangeriana.

Four new lignans, two of the polygamatin-type, named erlangerin A (1) and erlangerin B (2), and two related to podophyllotoxin, named erlangerin C (3) and erlangerin D (4), were isolated from the resin of Commiphora erlangeriana, a plant occurring in Ethiopia and Somalia. The structures of these compounds including their relative stereochemistry were elucidated on the basis of spectral evidence, chemical data, and X-ray crystallographic analysis.

Furanosesquiterpenes from Commiphora sphaerocarpa and related adulterants of true myrrh.

A new furanosesquiterpene, (1E)-8,12-epoxygermacra-1,7,10,11-tetraen-6-one (3), was isolated from the resin of Commiphora sphaerocarpa together with the known compounds curzerenone (1), furanodienone (2), (1E)-3-methoxy-8,12-epoxygermacra-1,7,10,11-tetraen-6-one (4), (1(10)E,2R*,4R*)-2-methoxy-8,12-epoxygermacra- 1(10),7,11-trien-6-one (5), and dihydropyrocurzerenone (6). Hydrodistillates of the resins of C. sphaerocarpa, C. holtziana, C. kataf and C. myrrha were analysed. The identifications were aided by NMR, GC and GC-MS.

Two octanordammarane triterpenes from Commiphora kua.

The resin of Commiphora kwo yielded two new octanordammarane triterpenes namely 15 alpha-hydroxymansumbinone and 28-acetoxy-15 alpha-hydroxymansumbinone, along with the four known compounds, mansumbinone, mansumbinol, (16S, 20R)-dihydroxydammar-24-en-3-one and T-cadinol. These structures were elucidated by spectroscopic techniques, including 1D and 2D NMR spectroscopy, and X-ray analysis.