Joseph O. Adebayo

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.

Testing of Natural Products and Synthetic Molecules Aiming at New Antimalarials

The search for new antimalarials, which in the past relied on animal models, is now usually performed with cultures of Plasmodium falciparum (PF) blood parasites by evaluation of parasite growth inhibition. Field isolates of PF human malaria parasite, parasite strains and clones, well characterized for their susceptibility to chloroquine and other standard antimalarials are available for the in vitro tests. The simplest method to evaluate parasite growth is the determination of parasitemias in Giemsa stained blood smears through light microscopy. Other methodologies have proven to be more precise and allow mass screening of new compounds against PF blood stages, such as: (i) measuring the incorporation of radioactive hypoxanthine by the parasites; (ii) indirect colorimetric assays in which specific parasite enzyme activities, and histidine-rich protein II (HRP2) production are measured with the help of monoclonal antibodies; (iii) the beta-haematin formation, and; (iv) assays using green fluorescent protein (GFP) in gene-expressing parasites. The advantages and disadvantages of the different in vitro screening methods, as well as the different in vivo models for antimalarial tests, are described in this review. Such tests can be used for the evaluation of medicinal plants, synthetic and hybrid molecules or drug combinations.

Effect of ethanolic extract of Khaya senegalensis on some biochemical parameters of rat kidney.

The effect of administration of ethanolic extract of Khaya senegalensis (2mg/kg body weight) on some biochemical parameters of rat kidney were investigated. Experimental animals were randomly divided into the control, those administered with the extract for 6 days and those administered with extract for 18 days, respectively. The prolonged administration of the extract resulted in significant reduction in the alkaline phosphatase activities of the kidney and its body weight ratio (P<0.05). In contrast, the same prolonged administration of the extract resulted in significant increase in the serum sodium ion concentration (P<0.05) while there was no significant difference in serum potassium ion concentration when compared to control (P>0.05). Administration of the extract for 6 days produced no significant difference from the control values in all the parameters investigated except in serum urea concentration which produced a significant increase (P<0.05). The available evidence in this study suggest that the ethanolic extract of Khaya senegalensis exerted more deleterious effect on the kidney when administered continuously over a prolonged period than a short one and this will adversely affect the functioning of the kidney.

Effects of Aqueous Extracts of Petals of Red and Green Hibiscus sabdariffa. on Plasma Lipid and Hematological Variables in Rats

Abstract The effects of administrating aqueous extracts of the petals of red and green Hibiscus sabdariffa. (1.0 and 1.5 mg/kg body weight) on hematological and plasma lipid variables were examined in rats. Animals were randomly divided into group A (control), groups B and C (treated with 1.0 and 1.5 mg/kg body weight, respectively, of the extract of petals of red Hibiscus sabdariffa.), and groups D and E (treated with 1.0 and 1.5 mg/kg body weight, respectively, of the extract of petals of green Hibiscus sabdariffa.). The chronic administration of both extracts for 28 days resulted in significant decreases in the plasma total cholesterol levels at 1.5 mg/kg body weight (p < 0.05) while the extracts led to significant decreases in LDL-cholesterol levels at both 1.0 and 1.5 mg/kg body weight only (p < 0.05). In contrast, the administration of the extracts did not have any significant effect on HDL-cholesterol, triglycerides, hematocrit, hemoglobin, red blood cell count, white blood cell count, and platelet count values when compared with the controls (p > 0.05). These results indicate that the lowered plasma total cholesterol concentrations induced by aqueous extracts of either red or green Hibiscus sabdariffa. petals is strongly associated with decreased LDL-cholesterol concentrations. Thus, both extracts could exert similar cardiovascular protective effects.

Chronic Administration of Aqueous Extract of Hibiscus sabdariffa. Enhances Na+-K+-ATPase and Ca2+-Mg2+-ATPase Activities of Rat Heart

Abstract The effect of oral administration of an aqueous extract of Hibiscus sabdariffa. Linn petals on Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities of rat heart have been investigated in Sprague-Dawley rats. The extract was administered orally in doses of 25.0 and 50.0 mg/kg body weight for 28 days. Results showed that Hibiscus sabdariffa. treatment led to significant increases (p < 0.001) of Na+-K+-ATPase and Ca2+-Mg2+-ATPase at both doses. Cardiac weight index of rats treated with H. sabdariffa. at a dose of 50 mg/kg body weight was significantly reduced (p < 0.01) compared with those of the control and rats treated with H. sabdariffa. at a lower dose. Administration of the extract at both doses did not show any signs of cardiotoxicity and hepatotoxicity as judged by biochemical “marker” enzymes (alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase) activities in plasma, heart, and liver of rats. These results demonstrate that aqueous extract of H. sabdariffa. enhances cardiac Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities and supports the public belief that H. sabdariffa. may be a safe cardioprotective agent.

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.

Mechanism-Based Inhibition of Myeloperoxidase by Hydrogen Peroxide: Enhancement of Inactivation Rate by Organic Donor Substrates

The effects of two hydrazine derivatives (isoniazid and hydralazine) on the inactivation of myeloperoxidase by H2O2 were investigated. Incubation of 20 nM myeloperoxidase with 0.25 mM H2O2 alone caused a time-dependent irreversible loss of tetramethylbenzidine oxidation activity with a pseudo-first order inactivation rate constant of 0.057 min -1 . The hydrazine derivatives increased the inactivation rate in a concentration-dependent manner. Inactivation of the enzyme by H2O2 with or without the hydrazides showed a saturation kinetics pattern. Steady state kinetics analysis suggests that the hydrazides likely inactivate myeloperoxidase using a similar inactivating species as does H2O2. A bimolecular rate constant, specific inactivation rate enhancement factor (k*enh) is proposed as a formal description of the inactivation rate stimulation by the hydrazides. This parameter potentially avoids confounding the finite inactivation due to H2O2 with that caused by the presence of the hydrazides. The relevance of these findings and the constants derived to the analysis of suicide inactivation of peroxidases by reductant substrates are discussed.

In vivo antimalarial activity and toxicological effects of methanolic extract of Cocos nucifera (Dwarf red variety) husk fibre

OBJECTIVE Phytochemical constituents as well as antimalarial and toxicity potentials of the methanolic extract of the husk fibre of Dwarf Red variety of Cocos nucifera were evaluated in this study. METHODS The dried powdered husk fibre was exhaustively extracted with hexane, ethyl acetate and methanol successively and the methanolic extract was screened for flavonoids, phenolics, tannins, alkaloids, steroids, triterpenes, phlobatannins, anthraquinones and glycosides. A 4-day suppressive antimalarial test was carried out using Plasmodium berghei NK65-infected mice, to which the extract was administered at doses of 31.25, 62.5, 125, 250 and 500 mg/kg body weight (BW). Toxicity of the extract was evaluated in rats using selected hematological parameters and organ function indices after orally administering doses of 25, 50 and 100 mg/kg BW for 14 d. RESULTS Phytochemical analysis revealed the presence of alkaloids, tannins, phenolics, saponins, glycosides, steroids and anthraquinones in the extract. Moreover, the extract reduced parasitemia by 39.2% and 45.8% at doses of 250 and 500 mg/kg BW respectively on day 8 post-inoculation. Various hematological parameters evaluated were not significantly altered (P>0.05) at all doses of the extract, except red blood cell count which was significantly elevated (P<0.05) at 100 mg/kg BW. The extract significantly increased (P<0.05) urea, creatinine, cholesterol, high-density lipoprotein-cholesterol and bilirubin concentrations in the serum as well as atherogenic index, while it reduced albumin concentration significantly (P<0.05) at higher doses compared to the controls. Alanine aminotransferase activity was reduced in the liver and heart significantly (P<0.05) but was increased in the serum significantly (P<0.05) at higher doses of the extract compared to the controls. CONCLUSION The results suggest that methanolic extract of the Dwarf red variety has partial antimalarial activity at higher doses, but is capable of impairing normal kidney and liver function as well as predisposing subjects to cardiovascular diseases.

Cysteine-stabilised peptide extract of Morinda lucida (Benth) leaf exhibits antimalarial activity and augments antioxidant defense system in P. berghei-infected mice.

ETHNOPHARMACOLOGICAL RELEVANCE Cysteine-stabilised peptides (CSP) are majorly explored for their bioactivities with applications in medicine and agriculture. Morinda lucida leaf is used indigenously for the treatment of malaria; it also contains CSP but the role of CSP in the antimalarial activity of the leaf has not been evaluated. AIM OF THE STUDY This study was therefore performed to evaluate the antimalarial activity of partially purified cysteine-stabilised peptide extract (PPCPE) of Morinda lucida leaf and its possible augmentation of the antioxidant systems of liver and erythrocytes in murine malaria. MATERIALS AND METHODS PPCPE was prepared from Morinda lucida leaf. The activity of PPCPE was evaluated in vitro against Plasmodium falciparum W2 and its cytotoxicity against a BGM kidney cell line. PPCPE was also evaluated for its antimalarial activity and its effects on selected liver and erythrocyte antioxidant parameters in P. berghei NK65-infected mice. RESULTS PPCPE was not active against P. falciparum W2 (IC50: >50µg/ml) neither was it cytotoxic (MLD50: >1000µg/ml). However, PPCPE was active against P. berghei NK65 in vivo, causing 51.52% reduction in parasitaemia at 31.25mg/Kg body weight on day 4 post-inoculation. PPCPE significantly reduced (P < 0.05) malondialdehyde concentrations in the liver and erythrocyte at higher doses compared to untreated controls. PPCPE increased glutathione concentration and activities of glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase in a dose-dependent manner, which was significant (P < 0.05) at higher doses compared to the untreated controls. CONCLUSION The results suggest that PPCPE may require bioactivation in vivo in order to exert its antimalarial effect and that PPCPE may augment the antioxidant defense system to alleviate the reactive oxygen species-mediated complications of malaria.

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.