Vitamin C-rich juice co-administration with artemether-lumefantrine ameliorates oxido-inflammatory responses in Plasmodium berghei-infected mice.

This study investigated the effects of co-administration of a commercial juice rich in vitamin C (Vit C) on the antimalarial efficacy of artemether-lumefantrine (AL) in Plasmodium berghei-infected mice. Fifty Balb/c mice were infected with Plasmodium berghei NK65 strain from a donor mouse. Parasitemia was established after 72 h. Animals were grouped into 6 (n = 10) and treated daily for 3 days with normal saline, chloroquine, artemether-lumefantrine (AL), AL plus 50% commercial juice (CJ), and AL plus 50% Vit C supplementation in drinks ad libitum, respectively. Body weight, parasitemia levels, and mean survival time were determined. Tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), nitrite, malondialdehyde, reduced glutathione (GSH), catalase, and superoxide dismutase (SOD) were determined in the serum and liver tissues. Spleen histopathological changes were determined by H&E staining. Parasitemia was cleared by administration of AL and was not affected by Vit C and CJ supplementation. Vit C significantly prevented body weight reduction in AL-treated mice. CJ and Vit C supplementation to AL-treated mice significantly improved survival proportion compared with AL alone animals. Vit C and CJ supplementation significantly improved reduction of TNF-α, IL-6, and malondialdehyde, and increased GSH, CAT, and SOD in AL-treated mice. Spleen cell degeneration and presence of malaria pigment were reduced in AL-treated animals. The results suggest that ad libitum co-administration of commercial juice and vitamin C with artemether-lumefantrine does not impair its antimalarial efficacy but rather improved antioxidant and anti-inflammatory effects in mice.

Serum cytokine profile of pregnant women with malaria, intestinal helminths and HIV infections in Ibadan, Nigeria.

Malaria, helminthiasis and HIV are widespread in developing countries taking a heavy toll on pregnant women. Due to similar environmental and human factors of transmission, they co-exist. The epidemiology and pathology of these diseases have been extensively studied but data on serum cytokine profile changes which is crucial in pregnancy is limited. The aim of this study was to evaluate the co-infections and their impact on peripheral blood cytokines. Blood and stool samples were collected from recruited 18-45-year-old pregnant women in different trimesters who were apparently healthy with no obvious complications in pregnancy. Pretested questionnaires were administered for personal and socio-demographic details. Malaria parasitemia in Giemsa-stained thick blood films was examined microscopically. Stool samples were screened for helminths using Kato-Katz method. Cytokine levels of TNF-α, IFN-γ, IL-1α, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-13 and IL-17 in 121 serum samples were determined using ELISA. Data were analysed using descriptive statistics and Mann-Whitney U test at α0.05. Relative to the single infections, there were significant reductions in IFN-γ and IL-13 in second and third trimesters respectively in those with Plasmodium and helminth co-infection. IFN-γ and IL-17 were elevated while IL-1α and IL-12p70 were reduced in co-infection of helminths and HIV. Co-infection of Plasmodium and HIV in second and third trimesters showed significant elevations in IL-1α, IL-10 and IL-17 while TNF-α, IL-4 and IL-12p70 were significantly reduced. HIV in pregnancy and its co-infection with Plasmodium resulted in significant distortions in the cytokine profile. However, helminth and its co-infection with Plasmodium or HIV produced less changes in the cytokine profile.

Non-Malaria Causes of Fever among under-5 Children with Negative Results for Malaria Rapid Diagnostic Test in South-Western Nigeria.

BACKGROUND: Although the global malaria burden is decreasing, there are still concerns about overdiagnosis of malaria and the danger of misdiagnosis of non-malaria causes of fever. Clinicians continue to face the challenge of differentiating between these causes despite the introduction of malaria rapid diagnostic tests (mRDTs). AIM: To determine the prevalence and causes of non-malaria-caused fever in children in South-Western Nigeria. METHODS: Secondary analysis of data obtained to evaluate the effect of restricting antimalarial treatment to positive mRDT children in rural and urban areas of southwest Nigeria. Clinical examinations, laboratory tests for malaria parasites (including thick blood film and mRDT) and bacterial identification were performed on children aged 3-59 months (n = 511). The non-malaria group comprised febrile children who had both negative mRDT and microscopy results, while the malaria group included those who were positive for either mRDT or microscopy. We compared the causes of fever among children with non-malaria fever and those with malaria. RESULTS: The prevalence of non-malaria fever and bacteria-malaria co-infection was 37.2% and 2.0%, respectively. Non-malarial pathogens identified were viral (54.7%) and bacterial (32.1%) infections. The bacterial infections included bacteriaemia (2.7%), urinary tract infections (21.6%), skin infections (11.6%) and otitis media (2.6%). The leading bacterial isolates were Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pneumoniae. CONCLUSION: The high prevalence and wide range of non-malarial infections reinforces the need for point-of-care tests to identify bacterial and viral infections to optimize the treatment of febrile illnesses in malaria-endemic areas.

Toxicity and Protective Effect of Phenolic-Enriched Ethylacetate Fraction of Ocimum gratissimum (Linn.) Leaf against Acute Inflammation and Oxidative Stress in Rats.

Preclinical Research Ocimum gratissimum L. leaves have attracted considerable attention from researchers because of their medicinal value that include anti-inflammatory, analgesic, antimicrobial, and antioxidant activities. In the present study, the toxicity and the protective effect of phenolic extract of O. gratissimum leaf (EAFOg) against acute inflammation and oxidative stress in rats was assessed. EAFOg, enriched in phenols had no cytotoxic effect against CHO-k1 cells, and no lethality against brine shrimp eggs or mice at a dose of 2000 mg/kg. EAFOg (50 and 100 mg/kg) reduced paw edema by 47% and 61%, compared to 29% with the COX-2 inhibitor, SC58125 (1 mg/kg) and 81% with indomethacin (5 mg/kg), respectively. In the rat carrageenan-induced air pouch model, EAFOg reduced exudate volume, leucocyte count, nitrite, TNF-α, and myeloperoxidase activity. EAFOg also protected against carrageenan-induced lipid peroxidation and glutathione depletion. These results provide evidence of the protective effects of EAFOg against acute inflammation and oxidative stress in rats. Drug Dev Res 78 : 135-145, 2017. © 2017 Wiley Periodicals, Inc.

Validation and pharmacokinetic application of a high-performance liquid chromatographic technique for determining the concentrations of amodiaquine and its metabolite in plasma of patients treated with oral fixed-dose amodiaquine-artesunate combination in areas of malaria endemicity.

Artemisinin-based combination therapies (ACTs) have been adopted by most African countries, including Nigeria, as first-line treatments for uncomplicated falciparum malaria. Fixed-dose combinations of these ACTs, amodiaquine-artesunate (FDC AQAS) and artemether-lumefantrine (AL), were introduced in Nigeria to improve compliance and achieve positive outcomes of malaria treatment. In order to achieve clinical success with AQAS, we developed and validated a simple and sensitive high-performance liquid chromatography (HPLC) method with UV detection for determination of amodiaquine (AQ) and desethylamodiaquine (DAQ) in plasma using liquid-liquid extraction of the drugs with diethyl ether following protein precipitation with acetonitrile. Chromatographic separation was achieved using an Agilent Zorbax C18 column and a mobile phase consisting of distilled water-methanol (80:20 [vol/vol]) with 2% (vol/vol) triethylamine, pH 2.2, at a flow rate of 1 ml/min. Calibration curves in spiked plasma were linear from 100 to 1,000 ng/ml (r > 0.99) for both AQ and DAQ. The limit of detection was 1 ng (sample size, 20 µl). The intra- and interday coefficients of variation at 150, 300, and 900 ng/ml ranged from 1.3 to 4.8%, and the biases were between 6.4 and 9.5%. The mean extraction recoveries of AQ and DAQ were 80.0% and 68.9%, respectively. The results for the pharmacokinetic parameters of DAQ following oral administration of FDC AQAS (612/200 mg) for 3 days in female and male patients with uncomplicated falciparum malaria showed that the maximum plasma concentrations (C max) (740 ± 197 versus 767 ± 185 ng/ml), areas under the plasma concentration-time curve (AUC) (185,080 ± 20,813 versus 184,940 ± 16,370 h · ng/ml), and elimination half-life values (T 1/2) (212 ± 1.14 versus 214 ± 0.84 h) were similar (P > 0.05).

Perceptions and recommendations by scientists for a potential release of genetically modified mosquitoes in Nigeria.

BACKGROUND: The use of genetically modified mosquitoes (GMMs) for the control of malaria and other mosquito-borne diseases has been proposed in malaria-endemic countries, such as Nigeria, which has the largest burden in Africa. Scientists are major stakeholders whose opinions and perceptions can adversely affect the success of the trials of GMMs if they are not involved early. Unfortunately, information on the awareness of Nigerians scientists and their overall perception of the GMMs is practically non-existent in the literature. Therefore, this study aimed at understanding how receptive Nigerian scientists are to a potential release of GMMs for the control of malaria. METHODS: The sample consisted of 164 scientists selected from academic and research institutions in Nigeria. Data were collected from participants using a semi-structured, self-administered questionnaire. Questions were asked about the cause and prevention of malaria, genetic modification and biotechnology. Specific questions on perception and acceptable conditions for the potential release of GM mosquitoes in Nigeria were also covered. RESULTS: All participants cited mosquitoes as one of several causes of malaria and used various methods for household control of mosquitoes. The main concerns expressed by the scientists were that GMMs can spread in an uncontrolled way beyond their release sites (89%) and will mate with other mosquito species to produce hybrids with unknown consequences (94.5%). Most participants (92.7%) agreed that it was important that before approving the release of GMMs in Nigeria, there had to be evidence of contingency measures available to remove the GMMs should a hazard become evident during the course of the release. In general, a majority (83.5%) of scientists who participated in this study were sceptical about a potential release in Nigeria, while 16.5% of the participants were in support. CONCLUSIONS: Although a majority of the participants are sceptical about GMMs generally, most encourage the use of genetic modification techniques to make mosquitoes incapable of spreading diseases provided that there are contingency measures to remove GMMs if a hazard becomes evident during the course of the release.

Increased cancer risk in HIV-infected individuals occupationally exposed to chemicals: Depression of p53 as the key driver.

The growing exposure to occupational chemicals and the spread of human immunodeficiency virus (HIV) infection are major global health issues. However, there is little data on the carcinogenic risk profile of HIV-infected individuals who have been occupationally exposed to chemical mixtures. This study therefore investigated the levels of cancer risk biomarkers in HIV-infected individuals exposed to occupational chemicals, exploring the relationship between apoptotic regulatory and oxidative response markers as a measure of cancer risk. Study participants (mean age 38.35±0.72 years) were divided into four groups according to their HIV status and occupational chemical exposure: 62 HIV-positive exposed (HPE), 66 HIV-positive unexposed (HPU), 60 HIV-negative exposed (HNE), and 60 HIV-negative unexposed (HNU). Serum p53, ß-cell lymphoma-2 (bcl2), 8-hydroxydeoxyguanosine (8-OHdG), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured using standard methods. Clusters of differentiation 4 (CD4+) T-lymphocytes were enumerated using flow cytometry. Serum p53 and bcl2 levels in HPE (0.91±0.11ng/ml and 122.37±15.77ng/ml) were significantly lower than HNU (1.49±0.15ng/ml and 225.52±33.67ng/ml) (p < 0.05), respectively. Wildtype p53 and bcl2 were positively and significantly correlated with 8-OHdG (r = 0.35, p<0.001; r = 0.36, p<0.001) and SOD (r = 0.38, p<0.001; r = 0.39, p<0.001). After controlling for gender, age, BMI, and cigarette smoking, both HIV status and SOD activity were significantly associated with wildtype p53 and bcl2 (p < 0.05). Malondialdehyde was significantly higher in the HPE (0.72 ± 0.01 mg/ml) than in the HNE (0.68 ± 0.01 mg/ml) and HNU (0.67 ± 0.01 mg/ml) groups (p < 0.05). The HPE group showed significantly lower CD4 counts than the HNE and HNU groups. Individuals who are HIV-infected and occupationally exposed to chemicals have a constellation of depressed immunity, elevated oxidative stress, and loss of tumour suppressive functions, which together intensify cancer risk, providing valuable scientific and public health bases for preventive measures in this vulnerable population.

Effect of chloroquine, methylene blue and artemether on red cell and hepatic antioxidant defence system in mice infected with Plasmodium yoelii nigeriensis.

Reactive oxygen species are mediators of tissue injury and are involved in malaria infection. In this study, the status of red cell and hepatic oxidative stress and antioxidant defence indices were investigated during Plasmodium yoelii nigeriensis (P. yoelii) infection, and treatment with chloroquine (CQ), methylene blue (MB) or artemether (ART) in mice. P. yoelii infection caused a significant (p < 0.05) increase in oxidative stress as evidenced by the elevated level of malondialdehyde. This was followed by a significant decrease (p < 0.05) in hepatic antioxidant defence indices, viz. reduced glutathione (GSH) and glutathione-S-transferase (GST). Also, the red cell catalase activity was significantly (p < 0.05) lower in malaria infection, while there was no significant difference (p > 0.05) in the superoxide dismutase (SOD) activity of infected mice when compared to untreated normal. Treatment of infected mice with the three antimalarials showed that the drugs suppressed the parasitaemia in the order CQ > ART > MB. CQ, MB and ART treatment of infected mice caused a significant (p < 0.05) increase in the levels of hepatic GSH and GST. Specifically, CQ, MB and ART increased the levels of hepatic GSH by 108, 124 and 98 %, respectively, at day 6. Also, ART treatment of infected mice significantly (p < 0.05) elevated the red cell SOD level by 200 % at day 3. Taken together, the findings suggest that the antimalarial effect of CQ, MB and ART countered the P. yoelii-induced oxidative stress leading to the elevation of enzymatic and non-enzymatic antioxidants in the host system.

Evaluation of the performances of two rapid diagnostic tests (Cyscope®mini and Paracheck-Pf®) in the diagnosis of malaria among febrile children in southwest Nigeria.

OBJECTIVE: The aim of this study was to test the diagnostic performances of Cyscope®mini and Paracheck-Pf® for Plasmodium falciparum relative to microscopy. SUBJECTS AND METHODS: 209 children aged 6 months to 12 years presenting with symptoms suggestive of malaria were enrolled at the University College Hospital, Ibadan, Nigeria, within a period of 6 months. Malaria parasites were identified in capillary blood samples using Cyscope®mini (parasite DNA-based fluorescence microscope) and Paracheck-Pf® (an HRP-II-based test) with microscopy of Giemsa-stained thick blood films as reference gold standard. The overall performances were calculated using OpenEpi version 2.3 statistical package. 209 samples were performed for Cyscope®mini and light microscopy while 140 samples were done by Paracheck-Pf®. RESULTS: The prevalence of malaria parasitaemia by light microscopy was 22.0% (46/209), while those of Cyscope®mini and Paracheck-Pf® were 85.2% (178/209) and 32.1% (45/140), respectively. Parasite density ranged from 40 to 203,883/µl. Cyscope®mini and Paracheck-Pf® had sensitivities of 91.3 and 86.21%, respectively. The respective specificities were 16.56 and 81.98% for Cyscope®mini and Paracheck-Pf® with diagnostic accuracies of 33.01 and 82.86%. The diagnostic performances of the two rapid diagnostic tests were significantly different. CONCLUSION: Paracheck-Pf® performed better than Cyscope®mini for diagnosis of falciparum malaria and will be a good diagnostic tool for field studies.

Ananas comosus (L) Merrill (pineapple) fruit peel extract demonstrates antimalarial, anti-nociceptive and anti-inflammatory activities in experimental models.

ETHNOPHARMACOLOGY RELEVANCE: Pineapple (Ananas comosus) peel is a major waste in pineapple canning industry and it is reported to be used in ethnomedicine as a component of herbal remedies for malarial management. This study aimed to evaluate the antimalarial, antinociceptive and anti-inflammatory properties of Ananas comosus peel extract (PEAC). METHODS: Ananas comosus peel was extracted with 80% methanol. PEAC (100, 200 and 400 mg/kg) was investigated for antimalarial effect using Peter's 4-day suppressive test (4-DST) model in mice. Antinociceptive activity of PEAC was investigated in hot plate, acetic acid-induced writhing and formalin tests in mice. The anti-inflammatory activity was evaluated using the lipopolysaccharides-induced sickness behavior in mice and carrageenan-induced air pouch in rats' models. RESULTS: PEAC could not significantly (p > 0.05) suppressed parasitemia level at 7-day post-infection in 4-DST. PEAC (400 mg/kg) mildly prolongs survival of infected mice up till day 21. PEAC demonstrated significant (p < 0.05) antinociceptive activity by increasing latency to jump on the hot plate, reduced number of writhings in acetic acid test and reduced paw licking time in 2nd phase of formalin test. PEAC significantly reduced anxiogenic and depressive-like symptoms of sickness behavior in LPS-injected mice. PEAC demonstrated significant anti-inflammatory activity in carrageenan-induced air pouch experiment by reducing exudates formation, inflammatory cell counts, and nitrite, tumor necrosis factor-alpha and interleukin-6 levels. CONCLUSION: Ananas comosus peel extract demonstrated mild antimalarial activity but significant anti-nociceptive and anti-inflammatory properties probably mediated via inhibition of pro-inflammatory mediators.

Antimalarial and antioxidant activities of methanolic extract of Nigella sativa seeds (black cumin) in mice infected with Plasmodium yoelli nigeriensis.

The antimalarial and antioxidant activities of methanolic extract of Nigella sativa seeds (MENS) were investigated against established malaria infection in vivo using Swiss albino mice. The antimalarial activity of the extract against Plasmodium yoelli nigeriensis (P. yoelli) was assessed using the Rane test procedure. Chloroquine (CQ)-treated group served as positive control. The extract, at a dose of 1.25 g/kg body weight significantly (p<0.05) suppressed P. yoelli infection in the mice by 94%, while CQ, the reference drug, produced 86% suppression when compared to the untreated group after the fifth day of treatment. P. yoelli infection caused a significant (p<0.05) increase in the levels of red cell and hepatic malondialdehyde (MDA), an index of lipid peroxidation (LPO) in the mice. Serum and hepatic LPO levels were increased by 71% and 113%, respectively, in the untreated infected mice. Furthermore, P. yoelli infection caused a significant (p<0.05) decrease in the activities of superoxide dismutase, catalase, glutathione-S-transferase and the level of reduced glutathione in tissues of the mice. Treatment with MENS significantly (p<0.05) attenuated the serum and hepatic MDA levels in P. yoelli-infected mice. In addition, MENS restored the activities of red cell antioxidant enzymes in the infected mice to near normal. Moreover, MENS was found to be more effective than CQ in parasite clearance and, in the restoration of altered biochemical indices by P. yoelli infection. These results suggest that N. sativa seeds have strong antioxidant property and, may be a good phytotherapeutic agent against Plasmodium infection in malaria.

Malaria, Helminth Infections and Clinical Status Among HIV-Infected Pregnant Women.

BACKGROUND OR OBJECTIVES: Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) is widespread in sub-Saharan Africa with similarity in geographical distribution of major pathogens of public health interest. The aim of this study was to assess the effect of malaria and helminths on CD4 count, hematocrit values and viral load among HIV-infected pregnant women. METHODS: One hundred and ninety-seven HIV-infected pregnant women aged 18-45 years were recruited from a registered HIV clinic and questionnaires were administered for socio-demographic details. Screening for malaria parasites in blood was through microscopy while helminths were identified in stool using Kato-Katz method. Hematocrit levels were determined through centrifugation of blood collected in capillary tubes. At the time of recruitment, most recent CD4 count and viral load was obtained from the patients' case notes. RESULTS: About three-quarters (73.6%) of the women had above primary school level of education while more than half (60.2%) were petty traders. The prevalence of malaria parasites in the blood samples was 24.9%, while 3% were infected with helminths. There was only a single case of malaria, helminths and HIV co-infection in the study group. Prevalence of anemia was 75.6% with eight cases (4.1%) of severe anemia. About 86.6% of the women with anemia had low CD4 count (χ2= 8.801, p=0.032). The mean CD4 count was significantly lower among those with co-infection of malaria and HIV. CONCLUSION AND GLOBAL HEALTH IMPLICATIONS: Malaria or helminth infection among HIV-infected women lowers the CD4 count and increases the viral load with little changes in hematocrit values. Routine screening of HIV-infected women for probable multiple infections will aid in improving their overall health and well-being.

An exegesis of bacteriophage therapy: An emerging player in the fight against anti-microbial resistance.

Bacteriophages (simply referred to as Phages) are a class of viruses with the ability to infect and kill prokaryotic cells (bacteria), but are unable to infect mammalian cells. This unique ability to achieve specific infectiousness by bacteriophages has been harnessed in antibacterial treatments dating back almost a decade before the antibiotic era began. Bacteriophages were used as therapeutic agents in treatment of dysentery caused by Shigella dysenteriae as far back as 1919 and in the experimental treatment of a wide variety of other bacterial infections caused by Vibrio cholerae, Staphylococcus sp., Pseudomonas sp. etc, with varying degrees of success. Phage therapy and its many prospects soon fell out of favour in western medicine after the Second World War, with the discovery of penicillin. The Soviet Union and other countries in Eastern Europe however mastered the craft of bacteriophage isolation, purification and cocktail preparation, with phage-based therapeutics becoming widely available over-the-counter. With the recent rise in cases of multi-drug resistant bacterial infections, the clamour for a return to phage therapy, as a potential solution to the anti-microbial resistance (AMR) crisis has grown louder. This review provides an extensive exposé on phage therapy, addressing its historical use, evidences of its safety and efficacy, its pros and cons when compared with antibiotics, cases of compassionate use for treating life-threatening antibiotic-resistant infections, the limitations to its acceptance and how these may be circumvented.

Contributions of malaria, helminths, HIV and iron deficiency to anaemia in pregnant women attending ante-natal clinic in SouthWest Nigeria.

BACKGROUND: Iron deficiency is a dominant source of anaemia in many settings. To evaluate the key cause of anaemia in the study area, the prevalence of anaemia due to major public health diseases was compared with anaemia due to iron deficiency. METHODS: Pregnant women were recruited from ante-natal (n=490) and HIV clinics (n=217) with their personal data documented using a questionnaire. Microscopy of Giemsa-stained thick smears was used for detection of malaria parasites while helminths in stools were detected using direct smear method. Haematocrit values were determined by capillary method. Serum ferritin levels were determined using enzyme-linked immunosorbent assay. Data was analysed using SPSS version 22.0. RESULTS: The mean age of the recruited women was 28.6±5.4 years old. There were 68.1% cases of anaemia of which 35.5% was due to infections only predominantly HIV and malaria, 14.9% from unknown sources while anaemia due to iron deficiency only was 7.1%. CONCLUSION: It can safely be inferred that malaria and HIV predispose to anaemia than iron deficiency in the study area. Although pregnant women are dewormed and given IPTp for helminths and malaria treatment respectively, there should be complementary routine malaria screening at ANC visits for those with HCT values <33% and those infected with HIV.

Flavonoid-Rich Fraction of Ocimum gratissimum Attenuates Lipopolysaccharide-Induced Sickness Behavior, Inflammatory and Oxidative Stress in Mice.

PURPOSE: Ocimum gratissimum L. leaves has been traditionally used for management of febrile illnesses and symptoms typified of sickness behavior. In this work we investigated the modulatory effect of flavonoid-rich fraction of O. gratissimum leaves (EAFOg) on sickness behavior, inflammatory and oxidative stress responses in LPS-challenged mice. METHOD: O. gratissimum leaf was first extracted with n-hexane, chloroform and methanol, and EAFOg was obtained by ethylacetate partitioning of a sequentially resultant methanol extract. The effect of EAFOg (25-100 mg/kg) on acute LPS-induced neurobehavioral impairment in an open field test (OFT) and depressive-like behavior in forced swimming test (FST) was investigated. Serum nitrite and TNF-α, as well as myeloperoxidase (MPO), malondialdehyde (MDA), and reduced glutathione (GSH) levels were determined in liver and brain tissues. RESULT: EAFOg prevented the reduction in locomotor and rearing activity in OFT and the increase in immobility time in FST. The fraction significantly attenuated the elevation of serum TNF- α and nitrite levels. EAFOg reversed LPS-induced increase in MDA, MPO, and nitrite levels and attenuated GSH depletion in liver and brain tissues of mice. CONCLUSION: Flavonoid-rich fraction of O. gratissimum leaf demonstrated significant modulation of LPS-induced sickness behavior, inflammatory and oxidative stress response in mice. This suggests an important therapeutic strategy in slowing down LPS-mediated hepatic and neuronal disease processes.

Ocimum gratissimum Linn. Leaf extract inhibits free radical generation and suppressed inflammation in carrageenan-induced inflammation models in rats.

BACKGROUND: Ocimum gratissimum leaf is used in managing rheumatism and other inflammatory conditions. In this study, we investigated the antioxidant and anti-inflammatory effects of phenolic extract obtained by sequential methanol extraction of O. gratissimum leaves (MEOg). METHODS: The methanol extract (MEOg) was obtained after sequential maceration (n-hexane, chloroform and methanol) of dried O. gratissimum leaves. The fingerprint of the extract was obtained using a high-performance liquid chromatrographic method. In vitro effects were tested by 1,1-Diphenyl-2-picryl-hydrazyl (DPPH), nitric oxide (NO) free radical scavenging, lipoxygenase, and xanthine oxidase inhibitory assays. MEOg was studied for anti-inflammatory activity in carrageenan-induced paw edema and air pouch inflammation in rats. RESULTS: HPLC fingerprint of the extract shows the presence of caffeic acid, rutin, ferulic acid, apigenin, and quercetin. Antioxidant activity of MEOg revealed an IC50 value in DPPH (31.5±0.03 µg/mL) and NO assay (201.6±0.01 µg/mL), respectively. The extract demonstrated strong xanthine oxidase inhibitory and weak antilipoxygenase activities. MEOg (100 mg/kg) significantly inhibited carrageenan-induced paw edema by 43.2%. Furthermore, MEOg (50 and 100 mg/kg) significantly reduced exudate volume, leucocyte count, neutrophil infiltration, TNF-α, nitrites, myeloperoxidase, and malondialdehyde in carrageenan-induced air pouch inflammation. MEOg also elevated the glutathione levels in the inflammatory exudates. CONCLUSIONS: MEOg shows potential therapeutic benefits in slowing down inflammation and oxidative stress in chronic diseases, such as arthritis.

Potential antimalarial activity of Methyl Jasmonate and its effect on lipid profiles in Plasmodium Berghei infected mice.

BACKGROUND: The antimalarial activity and lipid profiles of Methyl Jasmonate (MJ) were investigated against established malaria infection in vivo using BALB/c mice. METHODS: Arteether (AE) and chloroquine (CQ) were used as reference drugs while ethanol was used as the vehicle for drug delivery for MJ. RESULTS: Mice treated with 10 and 25 mg/kg MJ showed a remarkable reduction in percentage parasitemia by 68.3% and 78.2% on day 10(post treatment) respectively while 45.4% and 87.2% reduction in percentage parasitemia were observed in the group treated with 50 mg/kg on day 3 and 10 (post treatment) respectively. The highest mean survival time was observed in CQ followed by AE and MJ in dose-dependent manner. A progressive decrease in packed cell volume (PCV) was observed in infected untreated mice which led to the death of all the mice by day 9 (post treatment). Infected mice treated with MJ showed reduced level of HDL and LDL compared with infected untreated group. As the dose of MJ increased in infected mice cholesterol levels increased while there was reduction in triglyceride. CONCLUSION: Overall there was marked decrease in parasitemia in Plasmodium berghei infected mice treated with graded doses of MJ but appears to have reduced antimalarial activity compared with CQ and AE.

Studies on neuropharmacological profile of ethanol extract of Moringa oleifera leaves in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Moringa oleifera (family Moringaceae), commonly called Horseradish or tree of life, is traditionally used for the treatment of epilepsy and neurologic conditions. AIM OF THE STUDY: The objective of this study is to investigate the neurobehavioural and anticonvulsant properties of the ethanol extract from the leaves of Moringa oleifera. MATERIALS AND METHODS: Neurobehavioural properties were evaluated using the open field, hole board, Y-maze, elevated plus maze (EPM) and pentobarbitone-induced hypnosis. Pentylenetetrazole (leptazol), picrotoxin and strychnine induced convulsion tests were used to investigate the anti-convulsive actions of Moringa oleifera. RESULTS: The result showed that the extract (250-2000mg/kg) caused a significant dose-dependent decrease in rearing, grooming, head dips and locomotion (P<0.001). It also enhanced learning and memory and increased anxiogenic effect. In addition, the extract (2000mg/kg) protected mice against pentylenetetrazol induced convulsion, but has no effect on picrotoxin and strychnine induced convulsion. The effects of the extract in the various models were comparable to those of the standard drugs used except in Y-maze, EPM and picrotoxin and strychnine induced convulsion. The LD50 obtained for the acute toxicity studied using oral route of administration was >6.4g/kg. CONCLUSION: The findings from this study suggest that the ethanol extract of Moringa oleifera leaves possesses CNS depressant and anticonvulsant activities possibly mediated through the enhancement of central inhibitory mechanism involving release γ-amino butyric acid (GABA). The results partially justified the traditional use of the extract for the treatment of epilepsy.

Changes in antioxidant status and biochemical indices after acute administration of artemether, artemether-lumefantrine and halofantrine in rats.

Artemether, artemether-lumefantrine, or coartem and halofantrine are alternative antimalarial drugs to chloroquine. Their efficacy and potential to delay drug resistance in falciparum malaria had led to their increased use. Although these drugs have proven to be well tolerated, there are adverse effects associated with them. This study was designed to examine the toxic potential of acute administration of these drugs in rats. Twenty-four rats were divided into four groups: group I (control) received distilled water; group II received artemether for 5 days with an initial dose of 3.2 g/kg body weight on day 1 and 1.6 mg/kg body weight on days 2-5; group III received coartem (27 mg/kg body weight/day) for 3 days, which was divided into two equal portions per day; and group IV received halofantrine (24 mg/kg body weight/day) in three equal portions. Administration of artemether, coartem and halofantrine caused significant decrease (P < 0.05) in reduced glutathione levels in the liver by 29%, 21% and 26%, respectively. In contrast, there were no significant differences (P > 0.05) in the kidney glutathione levels. Furthermore, artemether, coartem and halofantrine decreased the liver- and kidney-enzymatic antioxidant status of the animals. Precisely, artemether, coartem and halofantrine decreased liver superoxide dismutase and catalase activities by 45%, 50% and 57%; and 20%, 29% and 23%, respectively. While the kidney catalase activities were decreased by 41%, 28% and 30%, respectively, the drugs however did not produce significant effect (P > 0.05) on the kidney superoxide dismutase activities. In addition, artemether, coartem and halofantrine decreased the hepatic levels of glutathione S-transferase by 64%, 51% and 53%, respectively. Administration of artemether, coartem and halofantrine significantly increased (P < 0.05) liver and kidney lipid peroxidation levels by 67%, 50% and 81%; and 58%, 43% and 31%, respectively. This indicates that the liver is considerably more affected than the kidneys. Similarly, halofantrine treatment caused significant elevation (P < 0.05) in the levels of serum creatinine, aspartate and alanine aminotransferases and blood urea nitrogen by 73%, 66%, 61% and 63%, respectively. These data indicate that oral administration of artemether, coartem and halofantrine has adverse effects on both enzymic and non-enzymatic antioxidant status of the animals.