Antiprotozoal activity of Khaya anthotheca, (Welv.) C.D.C. a plant used by chimpanzees for self-medication.

ETHNOPHARMACOLOGICAL RELEVANCE: Khaya species, endemic to Africa and Madagascar, continues to be valuable in indigenous traditional medicine. Their bitter tasting barks are decocted to treat fevers, several febrile conditions, microbial infections and worm infestations. In the Budongo rain forest of Western Uganda, non-human primates, especially chimpanzees and baboons, have been observed to eat the bitter non-nutritious bark and occasionally the seed. MATERIALS AND METHODS: Extracts were prepared by sequential fractionation with solvents of increasing polarities and assayed using standard procedures. Bioassay guided purification of the petroleum ether extract by column chromatography yielded three pure limonoids, Grandifolione (1), 7-deacetylkhivorin (2) and 1,3-deacetyldeoxyhavenensin (3). The antitrypanosomal, antileishmanial and antiplasmodial activities of pure compounds (1) and (2) were evaluated in vitro against Plasmodium falciparum K1, Trypanosoma brucei rhodesiense STIB 900, Trypanosoma cruzi trypomastigotes (Tulahuen C4), and axenic Leishmania donovani MHOMET-67/L82 and for cytotoxicity against L6 rat skeletal myoblast cells, in parallel with standard drugs. RESULTS: Of the four extracts tested, the petroleum ether extract showed activity against Plasmodium falciparum (IC50 0.955 µg/ml) and Trypanosoma brucei rhodesiense (IC50 5.72 µg/ml). The pure compounds (1) and (2) demonstrated activity against Plasmodium falciparum (KI strain) and marginal activities against Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania donovani. CONCLUSION: The present study provides evidence justifying the use of Khaya preparations in traditional medicine to treat fevers and microbial infections. The observed antiprotozoal activity of grandifolione and 7-deacetylkhivorin from the seed of Khaya anthotheca further confirms the ethnomedicinal potential of this plant and supports the hypothesis that non-human hominids (chimpanzees and baboons) too, eat the bitter bark and seeds for self-medication and in general, the use of Khaya plant material for medication by humans in disease endemic tropical areas. The antiprotozoal activity of gradifolione, and, the antitrypanosomal and antileishmanial activities of 7-deacetylkhivorin are reported here for the first time.

Regression analyses of southern African ethnomedicinal plants: informing the targeted selection of bioprospecting and pharmacological screening subjects.

ETHNOPHARMACOLOGICAL RELEVANCE: Regression analyses of local medicinal floras are considered potentially useful when prioritising candidate plant taxa for pharmacological/bioprospecting investigations. AIM OF THE STUDY: To identify plant orders and subsequently families within the highly diverse ethnomedicinal flora of southern Africa, towards which biases by traditional healers are demonstrable. Taxa so identified can subsequently be weighted appropriately in semi-quantitative selection systems. METHODOLOGY: Plant data sourced from the SANBI MedList database, the most comprehensive inventory of ethnomedicinal plants for the Flora of southern Africa region were grouped by order. A least squares regression analysis was applied to test the null hypothesis that the use of these plants by traditional healers is strictly random. Of 'hot' orders subsequently identified, characteristics of taxa therein were assessed to better determine the roles played by (i) growth forms, and (ii) inherent chemical diversity, in plant selections by ethnomedicinal practitioners. RESULTS: Analyses identified seven principally 'hot' plant orders (Malpigiales, Fabales, Gentianales, Asteraceae, Solanales, Malvales and Sapindales) and 'hot' families therein from a total of 55 regional ethnomedicinal orders. Five 'cold' ethnomedicinal orders (Rosales, Proteales, Poales, Asparagales and Caryophyllales) were shown to be significantly less represented in the medicinal flora than predicted. No clear growth form preferences were identified across orders. The presence of highly diverse bioactives was evident in the 'hottest' plant families from 'hot' plant orders. CONCLUSIONS: These 12 outliers identified by the regression analyses allowed for the falsification of the null hypothesis. Indications are that 'hot' taxa are selected traditionally on the basis of bioactivity, which is reflected in chemical diversity.

Low antiplasmodial activity of alkaloids and amides from the stem bark of Zanthoxylum rubescens (Rutaceae).

The stem bark of Zanthoxylum rubescens (syn. Fagara rubescens) is used for treating fevers associated with malaria in the Ivory Coast. Three alkaloids: N-nornitidine, 7,9-dimethoxy-2,3-methylenedioxybenzophenanthridine, and bis[6-5,6-dihydrochelerythrinyl)] ether; and two amides: zanthomamide and lemairamide, were isolated from the stem bark of this plant. These compounds were screened in vitro against the chloroquine-sensitive 3D7 strain and the chloroquine-resistant FCM29 strain of P. falciparum. N-nornitidine was found to be inactive. 7,9-dimethoxy-2,3-methylenedioxybenzophenanthridine, lemairamide and zanthomamide showed weak activity with average IC50 values ranging from 45.6 microM to 149.9 microM. Bis[6-15,6-dihydrochelerythrinyl)] ether was the most active of the tested compounds with mean IC50s of 14.9 +/- 1.4 microM in FCM29 strain and 15.3 +/- 3.4 microM in 3D7 strain (approximately 58 to approximately 1130 times less active than chloroquine respectively). The anti-Plasmodium activities of the tested alkaloids of Z. rubescens were low; and do not encourage the use of this plant as antimalarial.

The structural elucidation of a novel iridoid derivative from Tachiadenus longiflorus (Gentianaceae) using the LSD programme and quantum chemical computations.

Oleanolic acid, scoparone, scopoletin and a novel iridoid derivative, angelone, were isolated from Tachiadenus longiflorus (Gentianaceae). The structure of angelone was determined from NMR data, given as input to the Logic for Structure Determination Programme, and was finally confirmed by comparison of experimental 13C-NMR chemical shifts with those obtained by quantum mechanical calculations.

Evaluation of the mutagenic and antimutagenic effects of South African plants.

Dichloromethane and 90% methanol extracts of 42 South African plants were screened for mutagenicity and antimutagenicity using the Salmonella/microsome mutagenicity assay (Ames) against Salmonella typhimurium TA98 and TA100 bacterial strains in the presence and absence of metabolic activator S9. The methanol extracts from whole plants of Helichrysum simillimum, Helichrysum herbaceum and Helichrysum rugulosum indicated mutagenicity. These are the first reported tests on the mutagenicity of Helichrysum species. Six species indicated antimutagenic properties, all in the presence of S9: methanol leaf extract of Bauhinia galpinii, and dichloromethane leaf extracts of Bauhinia galpinii, Clerodendrum myricoides, Datura stramonium, Buddleja saligna, Millettia sutherlandii and Sutherlandia frutescens.

Investigations of the Malagasy species Tachiadenus longiflorus Grisebach (Gentianaceae): linking chemical finding and traditional usage.

A decoction of the aerial parts of Tachiadenus longiflorus, a Gentianaceae endemic to Madagascar, is drunk to relieve stomach pains and dyspepsia; while a leaf decoction is drunk as a purgative or to relieve gall bladder ailments in folk medicine in Madagascar. The stem and bark have yielded a large amount of the triterpenoid, oleanolic acid, and the coumarins, scoparone and scopoletin. These compounds have been isolated previously from other sources and have shown broad pharmacological properties. We report the possible link between the compounds isolated and the traditional use of Tachiadenus longiflorus.

Antiplasmodial diterpenoid from the leaves of Hyptis suaveolens.

Bioactivity-guided fractionation of the petroleum ether extract of the leaves of Hyptis suaveolens, widely used in Traditional Medicine, has led to the isolation of an abietane-type diterpenoid endoperoxide, 13 alpha-epi-dioxiabiet-8(14)-en-18-ol, displaying high antiplasmodial activity (IC(50) 0.1 microg/ml).

Phytochemical and pharmacological screening of Sterculiaceae species and isolation of antibacterial compounds.

Little previous phytochemical investigation has been conducted on South African Sterculiaceae species used in traditional medicine. In this study, five species, varying in growth type (small herbs, shrubs and large trees) and traditional usage were investigated. The species screened were Cola greenwayi Brenan, Cola natalensis Oliv., Dombeya burgessiae Gerr. ex Harv., Dombeya cymosa Harv. and Hermannia depressa N.E.Br. Extracts were screened for alkaloids, cardiac glycosides, cyanogenic glycosides, saponins and tannins. The probable presence of bufadienolides in the leaf material of Dombeya burgessiae and Dombeya cymosa was determined. Alkaloids, cyanogenic glycosides and saponins were absent in all the plant material investigated. Tannins were detected in the leaf extract of Cola greenwayi and in the leaves, stems and roots of Hermannia depressa. Extracts were screened for anti-inflammatory and antibacterial activity using the cyclooxygenase-1 (COX-1) inhibition assay and the microdilution antibacterial assay. The ethanol and dichloromethane extracts of Cola greenwayi, Dombeya burgessiae and Dombeya cymosa, and the dichloromethane extracts of Hermannia depressa showed the highest levels of COX-1 inhibition. It is possible that the high levels observed may be due to the presence of tannins in some of the extracts. Generally, all the aqueous extracts exhibited low activity. Similarly, no antibacterial activity was observed with the aqueous extracts, although some mild activity was exhibited with some of the ethanol and ethyl acetate extracts. Following the general phytochemical and pharmacological screening, extracts showing antibacterial activity were further purified using bioassay-guided fractionation. Dombeya rotundifolia (Hochst.) Planch., which was screened in a previous study, was also included in the isolation of active compounds. A bioautographic assay, using Staphylococcus aureus, was used to detect the presence of the antibacterial compounds. These were isolated and identified as fatty acids.

Chalconoid and stilbenoid glycosides from Guibourtia tessmanii.

Phytochemical studies on the stem bark of Guibourtia tessmanii yielded a dihydrochalcone glucoside, 2',4-dihydroxy-4'-methoxy-6'-O-beta-glucopyranoside dihydrochalcone and a new stilbene glycoside, 3,5-dimethoxy-4'-O-(beta-rhamnopyranosyl-(1-->6)-beta- glucopyranoside) stilbene besides the known pterostilbene. Their structures were established on the basis of one and two dimensional NMR spectroscopic techniques, FABMS and chemical evidence.

Bufadienolides from Drimia robusta and Urginea altissima (Hyacinthaceae).

The bufadienolides, 6beta-acetoxy-3beta,8beta,12beta,14beta-tetrahydroxybufa-4,20,22-trienolide (12beta-hydroxyscillirosidin) (1) and 14beta-hydroxybufa-4,20,22-trienolide 3beta-O-[alpha-L-rhamnopyranosyl-[(1-->4)-beta-D-glucopyranosyl]-(1-->3)-alpha-L-rhamnopyranoside] (urginin) (2) were isolated from Drimia robusta and Urginea altissima, respectively.

Supercritical fluid extraction and analysis of compounds from Clivia miniata for uterotonic activity.

In this descriptive study, the superciritical fluid extract of the roots of Clivia miniata L. was tested for uterotonic activity using guinea pig uterine smooth muscle in vitro. Extraction was performed with water modified supercritical carbon dioxide at 400 atm and 80 degrees C. The uterine contractions induced by this extract were compared to those induced by the aqueous extract and found to be active at lower doses. The active compounds were isolated and the structures elucidated by spectroscopic and chromatographic techniques. Both linoleic acid and 5-hydroxymethyl-2-furancarboxaldehyde isolated from the extract were found to induce muscle contractions individually. The pharmacological mode of action of 5-hydroxymethyl-2-furancarboxaldehyde was assessed using two receptor agonists and antagonists. This compound was found to mediate its effect through cholinergic receptors.

Idiopathic intracranial hypertension; incidence, presenting features and outcome in Northern Ireland (1991-1995).

OBJECTIVES: To determine the age and sex specific incidence rates, presenting features, and visual outcome of idiopathic intracranial hypertension in Northern Ireland. METHODS: A case-note review of all patients with idiopathic intracranial hypertension, diagnosed at the Royal Victoria Hospital, Belfast between 1991 and 1995. RESULTS: Forty-two patients were identified corresponding to an average annual incidence rate per 100,000 persons of 0.5 for the total and 0.9 for the female population. The commonest presenting symptoms were headache (84%), transient visual obscurations (61%) and sustained visual loss (34%). Impaired Snellen visual acuity and visual field loss were documented in 21% and 62% of patients respectively at presentation, and in 24% and 39% at last follow-up. One patient suffered deterioration in visual functioning sufficient to interfere with normal daily activities. CONCLUSIONS: The age and sex specific incidence rates of IIH in Northern Ireland are lower than have been reported in previous population-based series. Disabling visual loss occurs in a small number of patients despite all interventions.

Cyclooxygenase inhibiting and anti-bacterial activities of South African Erythrina species.

Aqueous, ethanolic and ethyl acetate extracts of the bark and leaves of five South African Erythrina species Erythrina caffra, Erythrina humeana, Erythrina latissima, Erythrina lysistemon and Erythrina zeyheri were screened for prostaglandin synthesis-inhibitory and anti-bacterial activity. The bark generally displayed higher activity than the leaves in both bioassays. The highest cyclooxygenase inhibiting activity and anti-bacterial activity was recorded for the ethanol and ethyl acetate bark extracts of E. caffra, E. latissima and E. lysistemon. An anti-bacterial compound, 4',5,7-trihydroxy-6-prenylisoflavone, was isolated by bioassay-guided fractionation from bark of E. lysistemon.

The uterotonic activity of compounds isolated from the supercritical fluid extract of Ekebergia capensis.

The wood of Ekebergia capensis Sparrm. is used by the local Zulu community in KwaZulu-Natal Province, South Africa to facilitate childbirth. In this investigation, the uterotonic properties of extracts from this tree were evaluated using both pregnant and non-pregnant guinea pig uterine smooth muscle in vitro. The extracts were prepared using water modified supercritical carbon dioxide at 400 atm and 80 degrees C. As samples of these extracts displayed positive results when screened for uterotonic activity, gravity column chromatography followed by NMR spectroscopy was performed in an attempt to isolate and elucidate the structures of the compounds that were present in the extract. The extract yielded five known compounds of which only two, viz. oleanonic acid and 3-epioleanolic acid, displayed uterotonic activity. Receptor binding assays were subsequently performed with 3-epioleanolic acid to ascertain its mode of action. Bradykinin (30 ng/100 microl) and acetylcholine (1 microg/100 microl) were used as the B2 and cholinergic receptor agonists respectively with icatibant (HOE 140) (30 ng/100 microl) and atropine (60 micro/100 microl) as their corresponding antagonists. 3-epioleanolic acid was observed to mediate its effect through the cholinergic receptor. The results of this study show that two compounds from the extract of this tree possess varying degrees of agonist activity on uterine smooth muscle with minor changes in the molecular structure affecting its intrinsic activity on uterine muscle.

Sesquiterpene lactone and friedelane derivative from drypetes molunduana.

A new sesquiterpene lactone, drypemolundein A and a new friedelane derivative, drypemolundein B, along with seven known compounds have been isolated from the whole stems of Drypetes molunduana Pax and Hoffm. Their structures were established on the basis of one- and two-dimensional NMR, homo- and hetero-nuclear spectroscopic evidence.