Ajuga remota Benth.: from ethnopharmacology to phytomedical perspective in the treatment of malaria.

Treatment and control of malaria have become more difficult with the spread of drug-resistant parasites and insecticide-resistant mosquito vectors. In the search for new antimalarial drugs, ethnopharmacological sources should merit more attention. Establishing the safety of traditional herbal medicines, along with identifying their active principles, are essential steps in the production of a properly standardized and accessible herbal medicine. Phytochemical characterization could also serve as a base for the development of new chemical compounds. The genus of Ajuga belongs to the family Lamiaceae and contains at least 301 species. Many of these plants have been used in traditional medicine. Ajuga remota in particular is traditionally used as a herbal remedy for fever and infections, and is prescribed for malaria by 66% of the Kenyan herbalists. A large number of compounds have already been isolated from A. remota, including ergosterol-5,8-endoperoxide (6), ajugarin-I (1), 8-O-acetylharpagide (5) and several phytoecdysteroids. In vitro pharmacological studies have been conducted on constituents of A. remota of which some of them displayed a concentration-dependent inhibition of chloroquine-sensitive and -resistant Plasmodium falciparum and Mycobacterium tuberculosis. Inhibition of parasitaemia was demonstrated in mouse models with P. berghei, supporting the traditional use of the plant against malaria. In this state-of-the-art review, A. remota as a possible therapeutic tool for malaria is discussed.

[St. Mary's Thistle: an overview]. / Le Chardon Marie: un aperçu.

St. Marys Thistle has been approved for registration as a regular medicine in Belgium. The hepatotropic properties of this plant are rather difficult to evaluate objectively. Mortality rate in case of life-threatening hepatic diseases is the most objective parameter. Legalon is the only drug registered in Belgium. It has a prescription only status. The plant Silybum marianum is a thistle and as a consequence belongs to the Compositae. There is a limited production of St.-Marys Thistle in Pajottenland, west of Brussels. The seeds are exported to Italy in order to extract silymarine, a mixture of flavonolignanes with antioxidant properties. Silymarine has been tested in living animals deliberately intoxicated with mushroom toxins, medicines, heavy metals or toxic organic solvents. Preventive as well as curative activity has been confirmed. Silymarine accumulates in the liver, which is also the target organ in therapy. Silymarine improves the prognosis after accidental ingestion of the toxic Amanita phalloides. Patients infected with hepatitis B and C might benefit from Silymarine, but more data have to be generated. Silymarine given to patients with liver damages by alcohol lowers the death toll. The drug has a general safety pattern comparable to placebo.

Antimalarial activity of Ajuga remota Benth (Labiatae) and Caesalpinia volkensii Harms (Caesalpiniaceae): in vitro confirmation of ethnopharmacological use.

Field trips to herbalists' practices in an area about 200 miles around Nairobi (Kenya) enabled us to make a list of medicinal plant species preferentially used to treat malaria. Ajuga remota and Caesalpinia volkensii were further investigated as being the most frequently used species. Aqueous decoctions, ethanol macerates, and petroleum ether, methanol and water Soxhlet extracts of these plants were further tested for their in vitro antimalarial properties in a chloroquine sensitive (FCA/20GHA) and resistant (W2) strain of Plasmodium falciparum. The activity was assessed by the parasite lactate dehydrogenase (pLDH) assay method. There was a concentration-dependent inhibition by the vegetal extracts of both plants. The IC(50) of the most active A. remota extract (ethanol macerate) was 55 and 57 microg/ml against FCA/20GHA and W2, respectively. For C. volkensii, it was the Soxhlet-water extract which was most active against FCA/20GHA with an IC(50) of 404 microg/ml while the petroleum ether extract exhibited the most activity against W2 with an IC(50) of 250 microg/ml. Further phytochemical work is being done in order to identify the active principles.

Hypoglycemic, anticomplement and anti-HIV activities of Spathodea campanulata stem bark.

Spathodea campanulata stem bark decoction (SCD) has shown hypoglycemic activity in mice. It was separated by column chromatography into different fractions, which were evaluated for their hypoglycemic, anticomplement and anti-HIV activities. The most polar fraction exerted by far the most prominent effect in different biological models.

Nutmeg oil: identification and quantitation of its most active constituents as inhibitors of platelet aggregation.

Three distilled or commercially available nutmeg oils were analysed and their chemical composition compared with their capacity to inhibit platelet aggregation in vitro. It could be clearly shown that eugenol and isoeugenol play the major role in the detected activity of nutmeg. Medicinally, it appears that nutmeg oil and nutmeg powder can be replaced by eugenol and/or isoeugenol.

Stereochemical considerations in relation to the pharmacological activity of Pterotaberna alkaloids.

Five 2-acylindole alkaloids, isolated from the leaves of Pterotaberna inconspicua, were pharmacologically investigated. The major alkaloids methuenine and 16-epimethuenine showed some interesting pharmacological features, whereas the minor alkaloids including 6-oxomethuenine and methuenine N-oxide were almost devoid of these pharmacological properties. Methuenine, being the most potent, was characterized as a non competitive antagonist against acetylcholine (pD'2=5.10 +/- 0.11) and histamine (pD'2 = 5.13 +/- 0.14) in guinea-pig ileum. Its potency was comparable to that of papaverine. 16-Epimethuenine behaved as a weak antihistaminic (pA2 = 6.55 +/- 0.08). The stereochemistry of both components is discussed in relation to their pharmacological activity.

Isolation and pharmacological characterization of vernolepin.

Vernolepin, a sesquiterpene lactone, was isolated from the dried fruit of Vernonia amygdalina Del. The different steps used during the extraction were: continuous extraction with chloroform, partition of the chloroform-extract between pertroleum ether and 10% aqueous methanol, column chromatography of the methanol extract, isolation of the active fractions by pharmacological and chemical characterization. Vernolepine was obtained as colorless prisms and identified by melting point, uv, ir, 1H nmr, optical rotation, and mass spectrometry. The total content of the dried fruit was 0.09% vernolepin. The first pharmacological characterization of vernolepin revealed: (1) a competitive antagonism against histamine in guinea pig ileum (pA2 = 5.61; 15 min incubation); (2) a biphasic enhancement/inhibition of coaxial stimulation of guinea pig ileum; (3) an antiaggregating and disaggregating activity against rabbit platelet aggregation induced by arachidonic acid (1 X 10(-4) g/ml; 3.3 X 10(-4)M) or ADP (4 X 10(-6) g/ml; 1 X 10(-5)M) without inhibition of cyclo-oxygenase or lipoxygenase. All these reactions were time dependent and occurred at concentrations of 5 X 10(-6) to 1 X 10(-5) g/ml vernolepin (1.8 to 3.5 X 10(-5)M).