Anti-trypanosomal activity of crude and nano-conjugated ethanol stem bark extracts of Sterculia setigera in mice

This study was carried out to screen for anti-trypanosomal activities of Sterculia setigera crude and nano-conjugated ethanol extracts of synthesized gold nanoparticles (AuNPs). Fresh stem bark of S. setigera was separately extracted with ethanol (ES) and aqueous (AS) followed by green synthesis/reduction of ethanol extract with AuNPs, and its formulation into nano-conjugate with the addition of standard drug Diminazine aceturate (berenil). The synthesized AuNPs were also characterized. Both the extracts and drug were separately administered toTrypanosoma brucei brucei infected animals orally at 200mg/kg bodyweight for 12 consecutive days. Two separate groups were infected untreated and infected treated with Diminazine aceturate (Berenil) to serve as positive and negative controls respectively. Similarly nano conjugates of S. satigera conjugate with the addition of standard drug Diminazine aceturate(berenil). The synthesized AuNPs were also characterized. Both the extracts and drug were separately administered to Trypanosoma brucei brucei infected animals orally at200mg/kg bodyweight for 12 consecutive days. Two separate groups were infected untreated and infected treated with Diminazine aceturate (Berenil) to serve as positive and negative controls respectively. Similarly nanoconjugates of S. satigera conjugate with the addition of standard drug Diminazine aceturate (berenil). The synthesized AuNPs were also characterized. Both the extracts and drug were separately administered to Trypanosoma brucei brucei infected animals orally at 200mg/kg bodyweight for 12 consecutive days. Two separate groups were infected untreated and infected treated with Diminazine aceturate (Berenil) to serve as positive and negative controls respectively. Similarly nanoconjugates of S. satigera and berenil were also orally administered to different groups of rats for 12 days consecutively. Theresults showed that the ethanol extract treated group recorded significant decrease in parasitaemia than the aqueous treated group when compared with the untreated controlgroups (p<0.05). Furthermore, treatment with both the nanoconjugates effectively cleared the parasites from the blood circulation of the infected animal (p<0.05). Bodyweight and PCV of treated groups improved significantly in all the treated animals (p<0.05). The ethanol extract ofS. setigera exhibited trypanostatic activity while its nano-conjugated was trypanocidal.

Trypanocidal effect of aqueous and ethanolic extracts of Strychnos spinosa on white mice infected with Trypanosoma brucei brucei

The emergence of trypanocidal resistance has led to a change in the behavior and use of local plants for the treatment of parasites. The trypanocidal activity of Strychnos spinosa aqueous and ethanolic extracts on Trypanosoma brucei brucei was evaluated during ten days of treatment. Thus, the smear was used to monitor the parasitaemia of mice treated with Strychnos spinose aqueous and ethanolic extracts by gavage at doses of 250, 500, 1000 mg/kg (test groups); with 10 ml/kg of distilled water (negative control) and 1mg/kg of isometamidium chloride (positive control). The results of the pharmacological studies on the trypanocidal potential of the plant showed that On day ten (D10) a mortality rates of 32 %, 39 % and 62 % respectively for the doses 250, 500 and 1000 mg/kg with the ethanolic extract while the aqueous extract induced a mortality rates of 32 %, 37 % and 56 % respectively. Isometamidium chloride induced the highest mortality rate of 85 %. The lethal doses were 218.07 and 225.79 mg/kg for the aqueous and ethanolic extracts respectively. All these results justify at least in part the use of this plant in traditional medicine for the treatment of trypanosomiasis. Keywords: Ethanolic extracts - Aqueous extracts - Trypanocidal potential - Trypanosomes - Inhibition of parasitaemia.

Infection of West African Dwarf Rams With Trypanosoma Brucei Brucei and Trypanosoma Congolense Significantly Alter Serum Electrolytes, Redox Balance, Sperm Parameters, And Gonadal Morphology

Trypanotolerance of the West African dwarf (WAD) breeds may not rule out significant pathophysiological changes that may affect productivity. In this study, the effects of infection of WAD rams with Trypanosoma brucei brucei (Tbb) and Trypanosoma congolense (Tc) on their serum levels of electrolytes [calcium, phosphorus, sodium, potassium]; oxidative stress markers [superoxide dismutase (SOD), malondialdehyde (MDA)]; and sperm parameters [sperm count, motility, vitality, and morphology] were investigated. Fifteen WAD rams, assigned to 3 groups (A, B & C) of 5 rams each, were used for the study. Group A rams were infected with Tbb, while Group B rams were infected with Tc, both intraperitoneally, at the dose of 106 trypanosomes/animal. Group C rams served as the uninfected control. The infections were monitored for 70 days. Serum calcium levels were significantly (p < 0.05) lower in Tbb and Tc infected rams compared to the control throughout the study. Serum sodium was significantly (p < 0.05) higher in the Tb infected rams compared to the Tc infected and control rams on days 14 and 28 PI. Serum SOD activity decreased while MDA levels increased in both infected groups of rams. Tbb infected rams were azoospermic, while Tc infected rams had lower sperm motility, vitality and concentration and higher number of abnormal sperm cells compared to the control. Necrotic and inflammatory lesions occurred in the testis and epididymis of both infected rams. These results suggest that in spite of trypanotolerance, trypanosome infections in the WAD rams significantly impact on health and reproduction.

Synthesis and Biological Profiles of Some Benzimidazolyl-chalcones as Anti-leishmanial and Trypanocidal Agents

Background: Benzimidazole constitutes a starting point for the development of new antiprotozoal agents since this nucleus exists in several pharmacologically significant molecules, in particular possessing antifungal, antiviral, antibacterial, and antiparasitic properties. Objective: The present study aimed to identify a molecular hit likely to be developed as an anti-leishmanial and antitrypanosomal drug candidate. Methods: Thus, 12 hybrids of chalcone or benzimidazolyl-arylpropenones were synthesized and screened in vitro for anti-leishmanial activity against promastigotes of Leishmania donovani. The microculture tetrazolium assay was used to determine their potential to inhibit 50% of a parasite growth (IC50). Results: Two compounds among 5-chlorobenzimidazole-chalcones (4a and 4c), which exhibited potent activity (IC50<1 μM) against L. donovani and one derivative (4d) poorly effective against L. donovani (IC50>50 μM) were selected to check their trypanocidal activity. Lethal concentration (LC100) values of these compounds were estimated by using observations on the viability of trypomastigotes of Trypanosoma brucei brucei in MEM medium with Earle’s salts and L-glutamine. Seven of the tested compounds (4a, 4b, 4c, 4e, 4g, 4h, and 4j) showed particularly higher inhibitory activity than pentamidine (IC50= 7.6 μM) against L. donovani promastigotes with IC50 values in a range from 0.5 to 1.8 μM. In addition, the 2’-chlorine derivative (4c), displayed potent anti-trypanosomal activity comparable to those of melarsoprol, used as reference drug. Conclusion: These results support this series of benzimidazole holding arylpropenone group in position 2 as a starting point for future optimization to get novel agents active against leishmaniasis and trypanosomiasis.

Anti-anaemic potential of the hydro-ethanolic extract of Waltheria indica (L) in albino rats with parasitaemia – induced anaemia

Anaemia has been reported to be the key feature of trypanosomiasis and is used as the primary indicator of when to treat the infection. Therefore, this study was designed to evaluate the anti-anaemic potential of the hydro-ethanolic extract of Waltheria indica in albino rats with parasitaemia – induced anaemia. Three groups of 6 rats each were challenged with Trypanosoma brucei brucei to induce anaemia and treated with 300mg/kg bw orally for 5 days, 3.5mg/kg Berenil® once intraperitoneally and distilled water. All the rats developed anaemia, manifested by significantly reduced values of Packed Cell Volume (PCV), Haemoglobin (Hb)concentration and Red Blood Cells (RBC) count within 5 days of infection compared with the pre-infection values. Treatment with Berenil and Waltheria indica hydro-ethanolic extract at 300mg/kg bw led to remarkable improvement in the values of the PCV, Hb and RBC, however, the restoration was significantly (P < 0.05) higher in the animals treated with the ethanol extract of the plant. Results of the study also indicated the absence of the effect of both parasitaemia and treatment on the levels of erythrocyte indices (Mean Cell Volume, Mean Cell Haemoglobin and Mean Cell Haemoglobin Concentration) of the infected rats. Therefore, the plant could be of use in the management of African sleeping sickness and other ailments related to anaemia.

In vitro culture of freshly isolated Trypanosoma brucei brucei bloodstream forms results in gene copy-number changes

Most researchers who study unicellular eukaryotes work with an extremely limited number of laboratory-adapted isolates that were obtained from the field decades ago, but the effects of passage in laboratory rodents, and adaptation to in vitro culture, have been little studied. For example, the vast majority of studies of Trypanosoma brucei biology have concentrated on just two strains, Lister 427 and EATRO1125, which were taken from the field over half a century ago and have since have undergone innumerable passages in rodents and culture. We here describe two new Trypanosoma brucei brucei strains. MAK65 and MAK98, which have undergone only 3 rodent passages since isolation from Ugandan cattle. High-coverage sequencing revealed that adaptation of the parasites to culture was accompanied by changes in gene copy numbers. T. brucei has so far been considered to be uniformly diploid, but we also found trisomy of chromosome 5 not only in one Lister 427 culture, but also in the MAK98 field isolate. Trisomy of chromosome 6, and increased copies of other chromosome segments, were also seen in established cultured lines. The two new T. brucei strains should be useful to researchers interested in trypanosome differentiation and pathogenicity. Initial results suggested that the two strains have differing infection patterns in rodents. MAK65 is uniformly diploid and grew more reproducibly in bloodstream-form culture than MAK98.