Iloneoside, an antimalarial pregnane glycoside isolated from Gongronema latifolium leaf, potentiates the activity of chloroquine against multidrug resistant Plasmodium falciparum.

The rapid spread of drug resistant malaria parasites has necessitated the search for novel antimalarials and chemosensitizers capable of reversing drug resistance in the parasites. A number of studies have revealed the resistance reversal activities of pregnane glycosides and the antimalarial activity of a pregnane glycoside obtained from Gongronema species. However, the pregnane (2) and pregnane glycosides (1, 3-4) isolated from Gongronema latifolium leaf have not been evaluated for these activities. This study was therefore carried out to evaluate the antiplasmodial and chloroquine resistance reversal activities of a pregnane and three pregnane glycosides isolated from G. latifolium leaf in vitro. The compounds were evaluated for their inhibitory activities against P. falciparum 3D7 (a chloroquine-sensitive strain) and P. falciparum W2 (a chloroquine-resistant clone) in vitro. The activities of chloroquine in separate combination with each of the compounds against P. falciparum W2 were also evaluated. Moreover, the interaction of the active compounds (1 and 4) with selected P. falciparum proteins (PfProteins) were evaluated in silico. The results revealed that only 1 and 4 were active against P. falciparum 3D7 and P. falciparum W2. Also, 2 and 3 did not exhibit chloroquine resistance reversal activity. Activity of chloroquine against P. falciparum W2 was potentiated by 1 by 3200% at concentrations higher than 0.625 µg/mL. Also, 1 and 4 demonstrated similar binding patterns and higher binding tendencies to the selected PfProteins compared to chloroquine. Thus, 1 (iloneoside) is an antimalarial pregnane glycoside which can potentiate the activity of chloroquine against multidrug resistant P. falciparum.

Morinda lucida Benth (Rubiaceae): A review of its ethnomedicine, phytochemistry and pharmacology.

ETHNOMEDICINAL RELEVANCE: Natural products derived from plants have served the primary healthcare needs of millions of indigenous people for centuries, many of which have been documented and scientifically validated. Morinda lucida Benth (Rubiaceae), also referred to as brimstone tree, is an ethnomedicinal plant which has been widely used in traditional medicine for several decades, particularly in the African continent. Various parts of the plant, including stem bark, leaves and root, have been applied in traditional medicine for the management of various pathological conditions such as malaria, diabetes, hypertension, inflammation, typhoid fever, cancer, cognitive disorders, sickle cell disease, trypanosomiasis, onchocerciasis and various fevers. In this review, we critically evaluated the relationship between traditional uses, laboratory pharmacological activities and clinical studies on M. lucida so as to unveil opportunities for the development of relevant therapeutic agents against diseases that threaten mankind. MATERIALS AND METHODS: A search for relevant data on M. lucida was done using scientific databases (Google Scholar, Mendeley, ScienceDirect, PubMed, Asian Science Citation Database, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chinese Scientific Journal Database, Chinese Science Citation Database, other web sources (such as The Plant List and PROTA), books and other literature sources. RESULTS: A hundred compounds have been isolated from M. lucida. Many of the reported secondary metabolites include alkaloids, tannins, anthraquinones, sterols, saponins, polyphenols, terpenoids, phenols and cardiac glycosides. The in vitro and in vivo experimental studies on various extracts, fractions and isolated compounds of M. lucida support the acclaimed pharmacological activities of the plant, such as antimalarial, antidiabetic, hypotensive, anti-inflammatory, immunostimulatory, antioxidant, antimicrobial, antiproliferative, cognitive-enhancement, anti-sickling, anti-trypanosomal, anti-onchocercal, muscle relaxant, antifungal and anti-leishmanial activities. These evidence-based scientific reports lend credence to their traditional uses. However, the safety of extracts of M. lucida is a cause for concern following reported toxicities such as antispermatogenic effect, genotoxicity and in vitro inhibition of human cytochrome P450 3A subfamily. CONCLUSION: Documented evidence suggests that M. lucida remains a rich source of extracts and chemical compounds with diverse bioactivities that are of therapeutic benefit to man and this justifies its traditional uses for the primary healthcare needs of indigenous populations across tropical Africa. Due to the fact that M. lucida extracts may not be safe at some reported doses, more in-depth studies on their toxicities are required to better understand safer approaches to their traditional uses. In addition, mechanistic studies on the isolated compounds with known pharmacological activities are quite limited, thus necessitating future research efforts to be focused on the mechanisms of action of these active principles in order to facilitate their potential enlistment for rational drug design.

Enhancing the antimalarial activity of artesunate.

The global challenge to the treatment of malaria is mainly the occurrence of resistance of malaria parasites to conventionally used antimalarials. Artesunate, a semisynthetic artemisinin compound, and other artemisinin derivatives are currently used in combination with selected active antimalarial drugs in order to prevent or delay the emergence of resistance to artemisinin derivatives. Several methods, such as preparation of hybrid compounds, combination therapy, chemical modification and the use of synthetic materials to enhance solubility and delivery of artesunate, have been employed over the years to improve the antimalarial activity of artesunate. Each of these methods has advantages it bestows on the efficacy of artesunate. This review discussed the various methods employed in enhancing the antimalarial activity of artesunate and delaying the emergence of resistance of parasite to it.

Cuprizone toxicity and Garcinia kola biflavonoid complex activity on hippocampal morphology and neurobehaviour.

Cuprizone-induced neurotoxicity has been employed to study the biology of remyelination in experimental models of multiple sclerosis. This study was aimed at determining the role of kolaviron, a biflavonoid from Garcinia kola, in mitigating the damaging effects of cuprizone on behaviour and the hippocampus. Twenty-four male albino mice aged 6-8 weeks were categorised into 4 equal groups: Group A (Control) received regular diet; Group B received 200 mg/kg/d of kolaviron in addition to their regular diet; Group C received 0.2% cuprizone diet only, while Group D received both kolaviron and cuprizone diet. The treatment lasted for 35 days after which behavioural tests (Morris water maze, Y maze and open field tests) were conducted and brain tissues were processed for histology, histochemistry (Nissl staining), immunohistochemistry (glial fibrillary acidic protein) and biochemistry (malondialdehyde, superoxide dismutase and glutathione peroxidase). Results showed that cuprizone toxicity led to weight loss, impairment in memory and exploratory drive, oxidative stress, chromatolysis and reactive astrocytosis; meanwhile administration of kolaviron prevented cuprizone-induced weight loss, memory decline, oxidative stress and neuromorphological alterations. In conclusion, administration of kolaviron might be useful in limiting the effects of cuprizone toxicity on the morphology and functions of the hippocampus.

Antimalarial Activity of Cocos nucifera Husk Fibre: Further Studies.

In this study, the antimalarial and toxicity potentials of husk fibre extracts of five Nigerian varieties of Cocos nucifera were evaluated in vitro. The only active extract fraction, West African Tall (WAT) ethyl acetate extract fraction, was then evaluated for its phytochemical constituents, antimalarial and toxicity potentials at varying doses (31.25-500 mg/kg body weight) using various organ function indices. The results revealed that WAT ethyl acetate extract fraction (WATEAEF) contained alkaloids, tannins, and flavonoids and was active against Plasmodium falciparum W2 strain maintained in continuous culture, with a selectivity index of 30.3. The same extract fraction was active in vivo against Plasmodium berghei NK65, causing more than 50% reduction in parasitaemia on days 4 and 6 after inoculation at various doses administered. WATEAEF did not significantly alter (P > 0.05) function indices of the liver and cardiovascular system at all doses administered but significantly increased (P < 0.05) plasma creatinine concentration at 250 and 500 mg/Kg body weight compared to controls. The results of this study suggest that WATEAEF possesses antimalarial activity and may not adversely affect normal liver function nor predispose subjects to cardiovascular diseases but may impair normal kidney function at higher doses. Further studies are underway to isolate the active principles.

Evaluation of the antiplasmodial and cytotoxicity potentials of husk fiber extracts from Cocos nucifera, a medicinal plant used in Nigeria to treat human malaria.

Nigeria is an African country where transmission of malaria occurs all year round and where most inhabitants use plants as remedies against parasitic diseases, including malaria. Some of such medicinal plants have their antimalarial efficacies already demonstrated experimentally, active compounds isolated and the mechanism of drug action suggested. Decoction of Cocos nucifera husk is used in the middle belt region of Nigeria as an antimalarial remedy. In our current studies, we tested extracts from husks of four varieties of C. nucifera, all collected in Brazil, where the plant fruit is popularly named 'coco'. The husks of coco mestiço, amarelo, anão and gigante collected in the Northeast of Brazil were used to prepare extracts at the Chemistry Department, Federal University of Alagoas (UFAL), which were then tested for their antiplasmodial activities, cytotoxicities and hemolytic activities in vitro. Only the hexane extract of coco mestiço was active against the blood forms of Plasmodium falciparum human malaria parasite maintained in continuous culture. Most extracts presented selectivity indices of <10, while hexane extract of coco mestiço had a selectivity index of 35, meaning that the extract is not toxic. The isolation of the active compounds from coco mestiço husks has not yet been done.

Effects of co-administration of artesunate and amodiaquine on some cardiovascular disease indices in rats.

The effects of co-administration of artesunate and amodiaquine on some cardiovascular disease indices were investigated in albino rats (Rattus novergicus). The experimental animals were randomly divided into four groups: those administered distilled water (control), those administered artesunate (2 mg/kg body weight), those administered amodiaquine (6.12 mg/kg body weight) and those co-administered artesunate (2 mg/kg body weight) and amodiaquine (6.12 mg/kg body weight). The drugs were orally administered twice daily for three days after which the serum lipid profile, heart MDA content and heart ALP and ACP activities were determined. Artesunate significantly reduced (P<0.05) total cholesterol and HDL-cholesterol concentrations in the serum with no significant effects (P>0.05) on other parameters compared to controls. Amodiaquine, on the other hand, significantly reduced (P<0.05) serum total cholesterol concentration while it significantly increased (P<0.05) serum LDL-cholesterol and heart ACP activity compared to controls. Co-administration of artesunate and amodiaquine significantly reduced (P<0.05) total cholesterol and HDL-cholesterol concentrations in the serum while significantly increasing (P<0.05) serum LDL-cholesterol concentration, atherogenic index (LDL-C/HDL-C) and ACP activity in the heart compared to controls. The results obtained suggest that co-administration of artesunate and amodiaquine to patients with coronary heart disease should be with caution.

Potential antimalarials from Nigerian plants: a review.

Malaria, caused by parasites of the genus Plasmodium, is one of the leading infectious diseases in many tropical regions, including Nigeria, a West African country where transmission occurs all year round. Many of the inhabitants use plants as remedies against fever and other symptoms of acute malaria, as reported herein. Some of these plants have their antimalarial efficacies scientifically demonstrated and the active compounds isolated with their probable mechanisms of action studied. Medicinal plants are used to treat diseases also where the biodiversity of plants occur in parallel with endemic transmission of malaria. This review focuses on medicinal plants which are used to treat malaria in Nigeria, and on antimalarial testing of extracts and purified compounds from plants. Some show intense activity against malaria parasites in vitro and in experimentally infected mice. The search for new drugs based on plants is important due to the emergence and widespread of chloroquine-resistant and multiple drug-resistant malaria parasites, which require the development of new antimalarials. An acquaintance with antimalarial plants may be a springboard for new phytotherapies that could be affordable to treat malaria, especially among the less privileged native people living in endemic areas of the tropics, mostly at risk of this devastating disease.

Effect of caffeine on the risk of coronary heart disease- A re-evaluation.

The effect of caffeine intake on the risk of coronary heart disease was studied. Twenty-one rats used were randomly divided into three experimental groups, the first group served as the control while the second and third groups were administered caffeine orally at doses of 10mg/kg body weight and 20mg/kg body weight respectively for fourteen days. Caffeine, at 10mg/kg body weight, significantly increased (P<0.05) serum LDL- cholesterol concentration and coronary heart disease risk ratio while it significantly reduced (P<0.05) serum triacylglycerol concentration when compared with controls. At 20mg/kg body weight, caffeine significantly increased (P<0.05) coronary heart disease risk ratio while it significantly reduced (P<0.05) serum HDL-cholesterol concentration and serum triacylgycerol concentration when compared with controls. No dose response effect was observed possibly suggestive of a threshold effect. These results suggest that caffeine predisposes consumers of caffeine containing beverages to coronary heart disease.

Haematological evaluation of ethanolic extract of Allium ascalonicum in male albino rats.

The haematological effect of ethanolic extract of Allium ascalonicum was evaluated in male albino rats during a 21 day administration at the doses of 50, 100 and 200 mg/kg b.w, orally. Parameters evaluated include the serum lipids, red and white cell indices. The results showed that the extract administered decreased most of the parameters relating to red cell and increased most of those parameters relating to white cells. It also decreased the total cholesterol (TCH), high density lipoprotein cholesterol (HDL) and low density lipoprotein cholesterol (LDL) with no significant effect on the triglyceride levels.

Campylobacter jejuni as a bacterial cause of diarrhoea in Ile-Ife, NIgeria.

A total of 495 diarrhoea and non-diarrhoea patients whose ages ranged between 5 and 39 years were examined for the presence of Campylobacter jejuni, Salmonella and Shigella species. About 12% of the specimens from diarrhoea patients were positive for Campylobacter jejuni compared with 6% and 10% for Salmonella and Shigella species. In contrast 2%, 0% and 1% of the samples from non-diarrhoea patients were positive for Campylobacter jejuni, Salmonella and Shigella species respectively. Most (62%) of the Campylobacter jejuni from diarrhoea patients were isolated from children under the age of 10 years. This compared with 26% and 37% for Salmonella and Shigella species in this age group. The frequency of isolation of Campylobacter jejuni in diarrhoea patients was highest during the dry months of the year. This study demonstrates the importance of Campylobacter jejuni as a major bacterial cause of diarrhoea in this part of the world.