5-HT2A/C receptors mediate the antipsychotic-like effects of alstonine.

The purpose of this study was to determine the effects of alstonine, an indole alkaloid with putative antipsychotic effects, on working memory by using the step-down inhibitory avoidance paradigm and MK801-induced working memory deficits in mice. Additionally, the role of serotonin 5-HT2A/C receptors in the effects of alstonine on mouse models associated with positive (MK801-induced hyperlocomotion), negative (MK801-induced social interaction deficit), and cognitive (MK801-induced working memory deficit) schizophrenia symptoms was examined. Treatment with alstonine was able to prevent MK801-induced working memory deficit, indicating its potential benefit for cognitive deficits now seen as a core symptom in the disease. Corroborating previously reported data, alstonine was also effective in counteracting MK801-induced hyperlocomotion and social interaction deficit. Ritanserin, a 5-HT2A/C receptor antagonist, prevented alstonine's effects on these three behavioral parameters. This study presents additional evidence that 5-HT2A/C receptors are central to the antipsychotic-like effects of alstonine, consistently seen in mouse models relevant to the three dimensions of schizophrenia symptoms.

Constituents of Peucedanum zenkeri seeds and their antimicrobial effects.

The methanol extract of Peucedanum zenkeri L. seeds showed antimicrobial activity which is concentrated in the n-hexane fraction. Bioactivity-guided chromatographic fractionation of the seeds of P. zenkeri led to the isolation and characterization of five major coumarins, umbelliprenin, imperatorin, bergapten, isopimpinellin and byakangelicin, as well as two minor coumarins, 7-methoxy coumarin and 5-hydroxy-8-methoxy psoralen. Amongst the isolated compounds only imperatorin, bergapten and isopimpinellin were found to possess anti-microbial activity.

Antipsychotic profile of alstonine: ethnopharmacology of a traditional Nigerian botanical remedy.

Although recently developed drugs have brought significant improvement, the treatment of psychotic disorders still presents serious drawbacks. Since inherent complexity and lack of satisfactory understanding of the underlying pathophysiology impose limits for rational drug design, resourceful approaches in the search for antipsychotics are pertinent. This paper reports pharmacological properties of alstonine, a heteroyohimbine type alkaloid, which exhibited an antipsychotic-like profile, inhibiting amphetamine-induced lethality, apomorphine-induced stereotypy and potentiating barbiturate-induced sleeping time. Atypical features of alstonine were the prevention of haloperidol-induced catalepsy and lack of direct interaction with D1, D2 and 5-HT2A receptors, classically linked to antipsychotic mechanism of action.

Antipsychotic profile of alstonine: ethnopharmacology of a traditional Nigerian botanical remedy

Although recently developed drugs have brought significant improvement, the treatment of psychotic disorders still presents serious drawbacks. Since inherent complexity and lack of satisfactory understanding of the underlying pathophysiology impose limits for rational drug design, resourceful approaches in the search for antipsychotics are pertinent. This paper reports pharmacological properties of alstonine, a heteroyohimbine type alkaloid, Which exbitited an antipsychotic-like profile, inhibiting amphetamine-induced lethaly, apomorphine-induced steotypy and potentiating barbiturate-induced slleping time. Atypical features of alstonine were the prevention of haloperidol-induced catalepsy and lack of direct interaction with D1, D2 and 5-HT2A receptors, classically linked to antipsychotic mechanism of action.

Anti-plasmodial sesquiterpenoids from the African Reneilmia cincinnata.

A new isodaucane sesquiterpenoid, 6,7,10-trihydoxyisodaucane, was isolated from the fruits of Reneilmia cincinnata, together with the known sesquiterpenoids oplodiol, oplopanone, 5E,10(14)-germacradien-1 beta, 4 beta-diol, 1(10)E,5E-germacradien-4 alpha-ol and eudesman-1,4,7-triol. A large amount of 5-hydroxy-3,7,4'-trimethoxyflavone was also isolated. Their structures were established by NMR techniques using 1D and 2D experiments. Three of the known sesquirernenoids exhibited noteworthy anti-plasmodial activity against Plasmodium falciparum strains.

Biodiversity prospecting in Nigeria: seeking equity and reciprocity in intellectual property rights through partnership arrangements and capacity building.

The regulation of genetic materials in Nigeria for the isolation of biologically active compounds and/or their exportation from the country fall under the purview of several government departments and parastatals. In principle, biological resources are considered similar to any other natural resource with different levels of stake holders. Specific restrictions, however, apply to the export of food crops. Nigeria is a traditional society where most of biodiversity belongs to what could be appropriately classified as public domain. It has therefore not been easy to carve out property rights from what is generally regarded as communal resources. Private access and occupancy of land and tenure are derived mainly from rights of membership of kindred groups or as custodian of "family' inheritance. The multi-state federal structure allows for negotiations to be conducted mainly at the level of the various State Government Departments responsible for forest resources, and the Federal Government providing the necessary policy guidelines and regulations. The Bioresources Development and Conservation Programme (BDCP), an international NGO based in Nigeria, has adopted an innovative model for biological prospecting based on establishing strategic partnerships and capacity building.

Biological activity of saponins from two Dracaena species.

Many species of the west African "soap tree" Dracaena are used in traditional medicine for the treatment of a variety of diseases. In continuation of our search for anti-infective agents from plants implicated in traditional medicine, we evaluated the biological activities of saponins from extracts of Dracaena mannii and Dracaena arborea by using a battery of test systems such as radiorespirometry, Cytosensor bioautography, and agar dilution methods and molluscicidal tests. Bioassay-directed fractionation of the methanol extracts of seed pulp using a combination of chromatographic techniques, gel filtration, droplet countercurrent chromatography (DCCC), and low-pressure liquid chromatography (Lobar), led to the isolation and characterization of spiroconazole A, a pennogenin triglycoside [3 beta-O-[(alpha-L-rhamnopyranosyl(1-->2), alpha-L-rhamnopyranosyl(1-->3)-beta-D-glucopyranosyl]-17 alpha-hydroxyl-spirost-5-ene] (Fig. 1). As the active constituent, spiroconazole A exhibited pronounced antileishmanial, antimalarial, and molluscicidal activities. This paper also reports on the fungistatic, fungicidal and bacteriostatic activity of spiroconazole A against 17 species of fungi and 4 of bacteria.

Natural product drug discovery and development: new perspectives on international collaboration.

Until recently, the prevailing attitude in developed nations regarded the world's genetic resources, which are mainly concentrated in the developing world, as a common resource of humankind, to be exploited freely irrespective of national origin. With the devastation being wreaked in the tropical rainforests and the resurgence in interest in recent years in the discovery of novel drugs from natural sources, particularly plants and marine organisms, the international scientific community has realized that the conservation of these global genetic resources and the indigenous knowledge associated with their use are of primary importance if their potential is to be fully explored. With this realization has come a recognition that these goals must be achieved through collaboration with, and fair and equitable compensation of, the scientists and communities of the genetically rich source countries. The signing of the United Nations Convention on Biological Diversity by nearly all of the World's nations has emphasized the need for the implementation of such policies. In this review, the articles of the Convention of relevance to the activities and practices of the natural products scientific community are briefly discussed. This discussion is followed by a summary of policies for international collaboration and compensation being implemented by several developed country organizations, and the perspectives on the current developments given by representatives of some of the source countries located in the regions of greatest biodiversity.

African medicinal plants in the search for new drugs based on ethnobotanical leads.

In the African world view the natural environment is a living entity whose components are intrinsically bound to mankind. Dietary plants, spices and common herbs dominate the materia medica, in contrast with modern orthodox medicine which uses many regulated poisons. Drug development based on ethnobotanical leads has followed two paths: the classical approach of identification of single plant species with biologically active compounds and the characterization and standardization of traditional recipes for reformulation as medicines. The first approach has led to the recognition of many African plants as medicines and the isolation of several biologically active molecules; examples range from the well physostigmine (from Physostigma venonosum) used for the treatment of glaucoma to the recently identified antiviral agents from Ancistrocladus abbreviatus. The second approach which aims at optimization of mixed remedies as formulated dosage forms is perhaps more relevant to the needs of the poor rural populations but has remained largely ignored. Drug development programmes based on ethnobotanical leads must provide for just and fair compensation for individual informants and local communities.

Medicinal plants in the fight against leishmaniasis.

Despite the tremendous progress mode in the understanding o f the molecular biology of Leishmania and the clinical possibilities presented by some experimental chemotherapeutic agents, no new drugs have been developed for the treatment of leishmaniasis since the introduction of the pentovalent antimoniols more than 50 years ago. As reviewed here by Maurice M. Iwu, Joan E. Jackson and Brion G. Schuster, recognition of the current extensive use of herbal therapy in Leishmania-endemic regions has renewed interest in evaluation of plant remedies used in traditional medicine as sources of potential antileishmanials.

Evaluation of plant extracts for antileishmanial activity using a mechanism-based radiorespirometric microtechnique (RAM).

Extracts of eleven plants used in Nigerian traditional medicine have been evaluated for possible antileishmanial activity using a radiorespirometric microtest technique based on in vitro inhibition of catabolism of 14CO2 from a battery of 14C-substrates by promastigotes. Of 13 methanol extracts tested, 5 from Gongronema latifolia, Dorstenia multiradiata, Picralima nitida, Cola attiensis, and Desmodium gangeticum, were active at concentrations of 50 micrograms/ml or less against a visceral Leishmania isolate.

Evaluation of the in vitro antimalarial activity of Picralima nitida extracts.

Extracts of Picralima nitida seeds, fruit rind, and stem bark have been investigated in vitro for antimalarial activity. The extracts showed remarkable inhibitory activity against drug resistant clones of Plasmodium falciparum at doses of 1.23-32 micrograms/ml. The dichloromethane extract of the fruit rind was the most active of the crude extracts, with IC50 values of 1.61 micrograms/ml for the Indochina (W-2), clone and 2.41 micrograms/ml for the Sierra Leone (D-6), clone. An alkaloid fraction obtained from the methanol extract of the stem bark gave an IC50 value of 2.00 micrograms/ml and 1.23 micrograms/ml in the W-2 and D-6 clones, respectively. The result supports the continued ethnomedical exploration of the plant as a potential antimalarial drug.

Hypoglycaemic activity of dioscoretine from tubers of Dioscorea dumetorum in normal and alloxan diabetic rabbits.

Dioscoretine isolated from the aqueous fraction of the methanol extract of Dioscorea dumetorum tubers when administered intra-peritoneally to normal and alloxan diabetic rabbits produces significant hypoglycaemic effects at a dose of 20 mg/kg. The fasting blood sugar in normoglycaemic rabbits was reduced from 112 mg/100 ml to 55 mg/100 ml after 4 hours. In alloxan diabetic rabbits, the blood sugar was lowered from 520 mg/100 ml to 286 mg/100 ml at the same time interval. The aqueous fraction of the methanol extract produced comparable effects at 100 mg/kg. The chloroform fraction of the same extract raised the fasting blood sugar of normal rabbits to 196 mg/100 ml after 6 h. The acute toxicity studies gave LD50 values of 1.4 g/kg for the aqueous fraction and 0.58 g/kg for dioscoretine when tested on mice. The hypoglycaemic effects were compared to those of tolbutamide.

Antidiabetic and aldose reductase activities of biflavanones of Garcinia kola.

Kolaviron, a mixture of C-3/C-8 linked biflavonoids obtained from Garcinia kola produces significant hypoglycaemic effects when administered intraperitoneally to normal and alloxan diabetic rabbits at a dose of 100 mg kg-1. The fasting blood sugar in normoglycaemic rabbits was reduced from 115 mg/100 mL to 65 mg/100 mL after 4 h. In alloxan diabetic rabbits, the blood sugar was lowered from 506 mg/100 mL to 285 mg/100 mL at 12 h. The hypoglycaemic effects have been compared with those of tolbutamide. Kolaviron inhibited rat lens aldose reductase (RLAR) activity, with an IC50 value of 5.4 x 10(-6). The significance of these findings in the potential use of kolaviron as an antidiabetic agent is discussed.

Evaluation of the antihepatotoxic activity of the biflavonoids of Garcinia kola seed.

Seeds of Garcinia kola enjoy a folk reputation in Africa as a poison antidote. Their antihepatotoxic properties have been evaluated using four experimental toxins, namely carbon tetrachloride, galactosamine, alpha-amanitin and phalloidin. Kolaviron, a fraction of the defatted ethanol extract, and two biflavones of Garcinia kola seeds (GB1 and GB2) significantly modified the action of all these hepatotoxins. At 100 mg/kg orally, the test substances reduced thiopental-induced sleep in CCl4-poisoned rats. The microsomal enzyme levels in the serum of mice poisoned with phalloidin were significantly protected by treatment with Garcinia extractives. The probable mechanism of the antihepatotoxic action is briefly discussed.