Mohammed Auwal Ibrahim

Anti-trypanosomal activity of African medicinal plants: A review update

ETHNOPHARMACOLOGICAL RELEVANCE African trypanosomiasis is one of the neglected tropical diseases caused by different species of trypanosomes that affect both human and livestock with devastating consequences in the continent. Most of the affected populations commonly use traditional medicinal plants for the treatment of the disease. Consequently, this prompted ethnopharmacological research activities on the anti-trypanosomal activity of a number of these African medicinal plants in order to validate their ethnomedicinal use. Furthermore, such studies could lead to the identification of chemical leads for the development of newer anti-trypanosomal agents from those plants. This review aims to provide updated information on the ethnopharmacological evidence of African medicinal plants with anti-trypanosomal activity. METHODS Literature was collected via electronic search (PubMed, Sciencedirect, Medline and Google Scholar) from published articles that report on the in vitro or in vivo anti-trypanosomal activity of plants that were collected from different parts of Africa. RESULTS African medicinal plants investigated for in vitro and in vivo anti-trypanosomal activity from January 1993 to October 2013 are systematically compiled and all the in vivo studies are critically discussed. A total of 264 plant species belonging to 79 families were investigated for anti-trypanosomal activity. However, only 48 bioactive anti-trypanosomal compounds were successfully isolated in pure forms. Furthermore, some of the plants were investigated for possible ameliorative effects on the trypanosome-induced pathological changes out of which 18 plants were reported to be effective while a few others were not. In spite of interesting preclinical ethnopharmacological evidence for anti-trypanosomal activity, not a single African medicinal plant was investigated in a clinical study. CONCLUSION Several African medicinal plants have demonstrated promising anti-trypanosomal effects but the studies on the anti-trypanosomal potentials of these plants are not taken beyond proof of concept stage. It is hoped that the article would stimulate future clinical studies because of the paucity of knowledge in this area.

The role of antioxidants treatment on the pathogenesis of malarial infections: a review

Oxidative damage is one of the most important pathological consequences of malarial infections. It affects vital organs of the body manifesting in changes such as splenomegaly, hepatomegaly, endothelial and cognitive damages. The currently used antimalarials often leave traces of these damages after therapy, as evident in memory impairment after cerebral malaria. Hence, some research investigations have focused attention on the use of antioxidants, alone or in combination with antimalarials, as a viable therapeutic strategy aimed at alleviating plasmodium-induced oxidative stress and its associated complications. However, the practical application of this approach often yields conflicting outcomes because some antimalarials specifically act via induction of oxidative stress. This article critically reviews most of the studies conducted on the potential role of antioxidant therapy in malarial infections. The most frequently investigated antioxidants are vitamins C and E, N-acetylcystein, folate and desferroxamine. Some of the investigations measured the effects of direct administration of the antioxidants on the plasmodium parasites while others performed an adjunctive therapy with standard antimalarials. The therapeutic application of each of the antioxidants in malaria management depends on the targeted aspect of malarial pathology. It is hoped that this article will provide an informed basis for future research activities on the therapeutic role of antioxidants on malarial pathogenesis.

Senna occidentalis leaf extract possesses antitrypanosomal activity and ameliorates the trypanosome-induced anemia and organ damage.

The in vitro and in vivo antitrypanosomal effects of the ethanol extract of Senna occidentalis leaf were investigated. The crude extract exhibited an in vitro activity against Trypanosoma brucei brucei as it completely eliminated parasites’ motility within 10 minutes postincubation with 6.66 mg/ml of effective extract concentration. The extract was further used to treat experimentally T. brucei brucei infected rats at concentrations of 100 and 200 mg/kg body weight, beginning on day 5 post infections (p.i.). At the termination of the experiment on Day 11 p.i., the extract significantly (P < 0.05) kept the parasitemia lower than was recorded in the infected untreated rats. All the infected animals developed anemia, the severity of which was significantly (P < 0.05) ameliorated by the extract treatment. The infection caused significant (P < 0.05) increases in serum alanine and aspartate aminotransferases as well as serum urea and creatinine levels. However, treatment of infected animals with the extract significantly (P < 0.05) prevented the trypanosome-induced increase in these biochemical indices. Furthermore, the T. brucei infection caused hepatomegaly and splenomegaly that were significantly (P < 0.05) ameliorated by the extract administration. It was concluded that orally administered ethanol extract of S. occidentalis leaf possessed anti-T. brucei brucei activity and could ameliorate the disease-induced anemia and organ damage.

Antioxidative activity and inhibition of key enzymes linked to type-2 diabetes (α-glucosidase and α-amylase) by Khaya senegalensis.

Abstract This study evaluated the in vitro antioxidative activity of Khaya senegalensis extracts and inhibitory effects of some solvent fractions on α-glucosidase and α-amylase activities. The stem bark, root and leaf samples of the plant were sequentially extracted with ethyl acetate, ethanol and water and then tested for antioxidative activity. Our findings revealed that the ethanolic extract of the root had the highest antioxidative activity. Solvent-solvent fractionation of the root ethanolic extract yielded a butanol fraction that showed higher antioxidative activity than other fractions. Furthermore, the butanol fraction had significantly higher (p < 0.05) α-glucosidase and α-amylase inhibitory activities with IC50 values of 2.89 ± 0.46 and 97.51 ± 5.72 μg mL-1, respectively. Enzyme kinetic studies indicated that the butanol fraction is a non-competitive inhibitor for α-glucosidase with an inhibition binding constant Ki of 1.30 μg mL-1 and a competitive inhibitor of α-amylase with a Ki of 7.50 μg mL-1. GC-MS analysis revealed that the butanol fraction contained two chromones, p-anilinophenol and 3-ethyl-5-(3- ethyl-(3H)-benzothiazol-2-ylidene)-2-(p-tolylvinylamino)- 4-thiazolidinone. Data obtained in the study suggest that the butanol fraction derived from the ethanolic extract of K. senegalensis root possessed excellent antioxidative as well as α-glucosidase and a-amylase inhibitory activities while chromones and/or p-anilinophenol could be the main bioactive compounds responsible for the observed activities.

A systematic review of pentacyclic triterpenes and their derivatives as chemotherapeutic agents against tropical parasitic diseases.

Parasitic infections are among the leading global public health problems with very high economic and mortality burdens. Unfortunately, the available treatment drugs are beset with side effects and continuous parasite drug resistance is being reported. However, new findings reveal more promising compounds especially of plant origin. Among the promising leads are the pentacyclic triterpenes (PTs) made up of the oleanane, ursane, taraxastane, lupane and hopane types. This paper reviews the literature published from 1985 to date on the in vitro and in vivo anti-parasitic potency of this class of phytochemicals. Of the 191 natural and synthetic PT reported, 85 have shown high anti-parasitic activity against various species belonging to the genera of Plasmodium, Leishmania, Trypanosoma, as well as various genera of Nematoda. Moreover, structural modification especially at carbon 3 (C3) and C27 of the parent backbone of PT has led to improved anti-parasitic activity in some cases and loss of activity in others. The potential of this group of compounds as future alternatives in the treatment of parasitic diseases is discussed. It is hoped that the information presented herein will contribute to the full exploration of this promising group of compounds as possible drugs for parasitic diseases.

Induction of Haemolysis and DNA Fragmentation in a Normal and Malarial-Infected Blood by Commonly - used Antimalarial Drugs in the North-Western Region of Nigeria.

BACKGROUND Antimalarial drugs are medicines that are used to prevent or treat malaria effectively at different stages in the life cycle of the malarial parasites. In spite of this, a good number of these drugs have the potential to cause harm when they are misused or abused. OBJECTIVE This study was undertaken to evaluate the effects of commonly-used antimalarial drugs in the North Western region of Nigeria on haemolysis and DNA fragmentation in the blood of normal and malarial infected humans ex vivo. METHOD The drugs used were artemisinine, artesunate, chloroquine, coartem and quinine (0.5-8.0 mg/ml). Haemolysis, haemoglobin status and DNA fragmentations were assayed for using standard procedures. RESULTS It was observed that all the drugs induced a remarkable dose-dependent haemolysis with more pronounced effects on apparently healthy humans. There was a significant (P < 0.05) decrease in the level of haemoglobin in normal blood samples when compared with control samples. Contrariwise, in the malaria-infected blood, the haemoglobin level significantly (P < 0.05) increased as compared with control. The drugs caused an exceptional significant (P < 0.05) induction of DNA fragmentation when compared with control. CONCLUSION Commonly-used antimalarial drugs induced haemolysis and altered haemoglobin status which may spontaneously increases the cellular iron levels; a substrate for Fenton and Haber Weiss reactions, and eventually induces DNA fragmentation. Hence, adequate care should be taken during prescription with total avoidance for self medications and/or drugs abuse as a result of their adverse effects within the red blood cells and its immediate microenvironment.

Saponins-rich fraction of Calotropis procera leaves elicit no antitrypanosomal activity in a rat model

OBJECTIVE To examine the in vitro and in vivo anti-Trypanosoma evansi (T. evansi ) activity of saponins-rich fraction of Calotropis procera (cpsf) leaves as well as the effect of the fraction on the parasite-induced anemia. METHODS A 60-minutes time course experiment was conducted with various concentrations of the fraction using a 96-well microtiter plate technique, and subsequently used to treat experimentally T. evansi infected rats at 100 and 200 mg/kg body weight. Index of anemia was analyzed in all animals during the experiment. RESULTS The cpsf did not demonstrate an in vitro antitrypanosomal activity. Further, the cpsf treatments did not significantly (P>0.05) keep the parasites lower than the infected untreated groups. At the end of the experiment, all T. evansi infected rats developed anemia whose severity was not significantly (P>0.05) ameliorated by the cpsf treatment. CONCLUSIONS It was concluded that saponins derived from Calotropis procera leaves could not elicit in vitro and in vivo activities against T. evansi.

The chemotherapeutic potential of chalcones against leishmaniases: a review

Leishmaniases are endemic diseases in tropical and sub-tropical regions of the world and are considered by the World Health Organization (WHO) to be among the six most important neglected tropical diseases. The current therapeutic arsenal against the disease is associated with a series of chemotherapeutic setbacks. However, since the early 1990s, naturally occurring chalcones with promising antileishmanial effects have been reported, and several other synthetic chalcones and chalcone-hybrid molecules have been confirmed to possess potent activity against various Leishmania species. This paper is a comprehensive review covering the antileishmanial activity of 34 naturally occurring chalcones, 224 synthetic/semisynthetic chalcones and 54 chalcone-hybrid molecules. Several chalcones in the synthetic/semisynthetic category had IC50 values < 5 µM, with very good selectivity against parasites, and the structure-activity relationships as well as the proposed mechanism of action are discussed. We identified knowledge-gaps with the hope of providing future direction for the discovery of novel antileishmanial drugs from chalcones.

Alteration of redox status by commonly used antimalarial drugs in the north-western region of Nigeria

This study was designed to investigate the alteration of redox status by commonly used antimalarials in Nigeria. Drugs used were artemisinin, artesunate, chloroquine, coartem and quinine at the final concentrations of 0.5–8.0 mg/mL. Blood samples were collected from malarial patients and apparently healthy humans for comparison. Reduced glutathione, catalase, superoxide dismutase (SOD) activities, protein content and lipid peroxidation were determined. All drugs significantly (p < 0.05) increases the protein level relative to control in normal blood, whereas in the infected, a significant (p < 0.05) reduction was observed. In normal blood, the antimalarials dose dependently decreased (p < 0.05) SOD and catalase activities with significant (p < 0.05) increase in the infected. The level of glutathione in normal blood significantly (p < 0.05) increases as compared with control, whereas in the infected, similar observation was made except that the levels were less, relative to control sample. Malondialdehyde level significantly (p < 0.05) increases with increase in drugs concentration even though less than the level in the control with few exceptions. These effects were dose dependent and more pronounced in non-malarial conditions. Commonly used antimalarials might alter the redox status in both healthy and non-healthy subjects thereby inducing oxidative stress.

Antioxidant Therapy Against Trypanosome Infections: A Review Update

Trypanosomiasis is a serious parasitic disease that affects humans and animals resulting in heavy health and economic burdens. Disturbance of redox equilibrium represents a classical challenge for both the host and the parasite during infections with either extracellular African or intracellular American trypanosomes species. This is in spite of existing detoxification mechanisms in both the host and the parasite for maintaining oxidative balance. However, oxidative stress still plays vital roles in the induction of numerous host-associated pathological damages such as anemia, hepatic and renal damages as well as cardiomyopathy while on the other hand, drugs that specifically induce oxidative stress to the parasite have been effective. Therefore, antioxidants have been deemed to play a role in modulating trypanosome infections. This review provides a current update on most of the studies conducted on the potential use of antioxidants as therapeutic agents against trypanosomes. The most frequently studied plant-derived phenolic antioxidants are resveratrol, cucurmin, gallic acid and quercetin while other antioxidants such as vitamins (A, C, E) and trace elements (selenium and iron) have been investigated. Some of the investigations monitored the direct trypanocidal or trypanostatic effects of the antioxidants while others studied the potentials of the antioxidants as adjuncts to trypanocidal drugs. So far, none of these approaches has sufficient data to allow a definite statement on the actual therapeutic potential of antioxidants in the treatment of clinical trypanosomiasis. Therefore, suggestions are made on the most therapeutically and clinically relevant role of antioxidants in trypanosome infections.