"Mango in all her majesty"-the potential of mangiferin and its analogues in the inhibition of Eimeria tenella hexokinase-a computational approach.

The potential of natural products in mitigating infections and diseases are being considered lately. Herein, via in silico methods, we report the possible molecular mechanism of mangiferin (isolated from the fruit, peel, bark and leaves of mango tree) and its derivatives in inhibiting Eimeria tenella hexokinase. We evaluated the binding affinity of these inhibitors to the glucose binding site of EtHK and thereafter proceeded to molecular dynamics simulation. The Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) reveals that three of the derivatives (CPAMM, MxPAMM and NAMM) had better total binding free energy than mangiferin. The ADMET and physicochemical properties assessed shows that inhibitors also hold a potential to be drug-likely. Finally, in mediating their inhibitory potentials, the ligands stabilize both the global and local structures of the protein. This study provides a theoretical premise on which the anti-coccidial propensities of mangiferin most especially its derivatives can be investigate in vitro and in vivo.Communicated by Ramaswamy H. Sarma.

Anthelmintic activity and non-cytotoxicity of phaeophorbide-a isolated from the leaf of Spondias mombin L.

ETHNOPHARMACOLOGICAL RELEVANCE: Helminthosis (worm infection) is a disease of grazing livestock, with significant economic implications. Increasing resistance to existing synthetic anthelmintics used to control helminthosis and the unwanted presence of residues of the anthelmintics reported in meat and dairy products present a serious global health challenge. These challenges have necessitated the development of novel anthelmintics that could combat drug resistance and exhibit better safety profiles. Spondias mombin L. (Anacardiaceae) is a plant that has been used traditionally as a worm expeller. AIM OF STUDY: The aim of the work reported herein was to isolate and characterise anthelmintic compound(s) from S. mombin leaf, establishing their bioactivity and safety profile. MATERIALS AND METHODS: Adult Haemonchus placei motility assay was used to assess anthelmintic bioactivity. Bioassay-guided chromatographic fractionation of acetone extract of S. mombin leaf was carried out on a silica gel stationary phase. The structure of the compound was elucidated using spectroscopy (1H and 13C NMR) and Liquid Chromatography-Mass Spectrometry (LC-ESI-MS). Screening to exclude potential cytotoxicity against mammalian cells (H460, Caco-2, MC3T3-E1) was done using alamar blue (AB) and CellTitreGlo (CTG) viability reagents. RESULTS: The acetone extract yielded an active fraction 8 (Ethyl acetate: methanol 90:10; anthelmintic LC50: 3.97 mg/mL), which yielded an active sub-fraction (Ethyl acetate: Methanol 95:5; anthelmintic LC50: 53.8 µg/mL), from which active compound 1 was isolated and identified as phaeophorbide-a (LC50: 23.0 µg/mL or 38.8 µM). The compound was not toxic below 200 µM but weakly cytotoxic at 200 µM. CONCLUSIONS: Phaeophorbide-a (1) isolated from S. mombin leaf extract and reported in the plant for the first time in this species demonstrated anthelmintic activity. No significant toxicity to mammalian cells was observed. It therefore represents a novel anthelmintic pharmacophore as a potential lead for the development of novel anthelmintics.

Pleurotus ostreatus extract inhibits Eimeria species development in naturally infected broiler chickens.

Coccidian organisms of poultry have proved very hard to control due to their abilities to resist most anticoccidial drugs. Pleurotus ostreatus (Fr.) Jacq. ex (Pleurotaceae), a medicinal mushroom, was investigated in vivo against Eimeria spp. Ninety-six broilers (day-old) naturally infected with Eimeria spp. were divided into eight groups (12 birds per group). Group A was infected untreated (negative control) and group B was treated with toltrazuril (positive control) while groups C-H were gavaged with graded doses of P. ostreatus extract at 100, 200, 300, 400, 500, and 600 mg/kg, respectively. The phytochemical analysis of the aqueous extract of P. ostreatus which revealed saponins, flavonoids, anthraquinones, and alkaloids was evaluated for anticoccidial activity by assessing the inhibition of oocyst output, lesion score, faecal score, weight differences, haematological parameters, and leucocyte differential counts. The acute toxicity study showed extract of P. ostreatus to be non-toxic at 600 mg/kg. The weight of the groups treated with the extracts and toltrazuril increased significantly (P < 0.05) compared with the untreated control. Treated groups significantly (P < 0.05) reduced oocyst output except groups C and D. The therapeutic best-fit ED50 value for the extract was 448 mg/kg. The post-treatment mean packed cell volume and red blood cell count were significantly higher (P < 0.05) than the untreated group, while the WBC count was significantly higher (P < 0.05) in the untreated group. Pleurotus ostreatus therefore could be a potential source of new anticoccidial medicine which could find application in the control of avian coccidiosis.

Dataset on continuous passages of Trypanosoma brucei in different laboratory animals.

Scientist in developing countries maintain trypanosomes in laboratory animals for in vivo experiments. We generated data on the adaptation of Trypanosoma brucei (NITR201 strain) in balb/c mice (forty-five, 18-23 g), wistar rats (fifteen, 180-220 g) and New Zealand white and chinchilla rabbits (fifteen, 2.8-3.0 kg) in a controlled experimental system. The weight, haematological parameters, course of parasitaemia, temperature, mean survival time and survival proportions of laboratory animals in groups A-E were collected and analysed for differences in response to the same challenge of quantity, strain and species of T. brucei. Trypanosome pleomorphism of long, intermediate to short-stumpy forms were among the dataset counts for parasitaemia. Statistical data after analysis were summarised in the supplementary file to show the differences and corresponding reaction of multiple passages.

Novel trypanocide from an extract of Pleurotus sajor-caju against Trypanosoma congolense.

CONTEXT: Control of African trypanosomiasis relies on chemotherapy, but the development of resistance and the problem of drug residues require research for alternatives. Triterpenes and phenolics, the major constituents of Pleurotus sajor-caju (Fr.) Singer (Pleurotaceae), are reported to be effective against trypanosomiasis. OBJECTIVE: Trypanocidal effect of whole Pleurotus sajor-caju aqueous extract was investigated in vivo against Trypanosoma congolense. MATERIALS AND METHODS: Mice (25-32 g) were divided into seven groups of six animals. Mice in groups A-F received 2.5 × 104 trypanosomes, while group G was uninfected. Extracts (100-250 mg/kg) were administered intraperitoneally for 5 days to groups A-D while diminazine aceturate (group E) and normal saline (group F) served as positive and negative controls, respectively. Parasitemia, survival time, body weight and haematological parameters were monitored for 60 days post-treatment. RESULTS: Parasitemia decreased significantly (p < 0.01) post-treatment with 200 and 250 mg/kg of the extract and became undetectable by day 16 and 12 post-infection, respectively; the ED50 was 221.5 mg/kg. The packed cell volume (PCV) and the weight of mice treated with 250 mg/kg extract were 46.20 ± 2.6% and 32.05 ± 3.63 g, respectively, which is higher than the group treated with diminazine aceturate. The mean survival time of animals in groups D and E was >60 days, while that of group F was <4 days. Differential leucocyte count on day 68 post-infection in groups C, D and E were not significantly different. CONCLUSION: Pleurotus sajor-caju therefore could be a potential source of new trypanocidal drugs.

Absence of detectable benzimidazole-resistance associated alleles in Haemonchus placei in cattle in Nigeria revealed by pyrosequencing of ß-tubulin isotype 1.

Trichostrongyles are gastrointestinal parasites that occur globally and can cause subclinical to severe, sometimes life-threatening, infections in ruminants, particularly young animals. Benzimidazoles (BZ) are commonly used for the treatment of gastrointestinal parasites in ruminants. Increasing spread of worm populations with anthelmintics resistance has been reported and is considered a consequence of highly frequent and longstanding use of anthelmintics. To obtain initial information regarding the occurrence of putatively BZ-resistant Nigerian Haemonchus populations, screening based on the molecular analysis of BZ-resistance-associated ß-tubulin isotype 1 gene sequence polymorphisms was undertaken. Genomic DNA was isolated from pooled adult Haemonchus sp. from 35 animals from each of the six states of southwestern Nigeria. Sequencing of internal transcribed spacer 2 (ITS-2) and external transcribed spacer (ETS) regions was used to determine the Haemonchus species. Pyrosequencing assays were used for detection of single-nucleotide polymorphisms (SNPs) in the ß-tubulin isotype 1 genes of the worms at codons 200 and 167 (TTC/TAC) or 198 (GAA/GCA). Exclusively, Haemonchus placei was detected and allele frequencies obtained at all three positions showed no evidence for the presence of resistance-related alleles. For Lagos State, pools of 10 worms from 30 different animals were analyzed separately for the codon 200 SNP, successfully excluding the presence of resistance-associated SNPs in very low frequencies. These positive findings, showing absence of elevated frequencies of BZ-resistance-associated ß-tubulin alleles, have considerable significance since it suggests that farmers can still rely on the efficacy of this important drug class when used for controlling trichostrongyle infections in cattle in Nigeria.