Safety and Efficacy of Prosopis Juliflora Leaf Extract as a Potential Treatment against Visceral Leishmaniasis
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Date
2020-03
Authors
Muendo, Charity Mutile
Journal Title
Journal ISSN
Volume Title
Publisher
Kenyatta University
Abstract
Leishmaniasis is a major health problem in the tropics and sub-tropic regions where it is endemic. The treatment of leishmaniasis is faced with several drawbacks. Up to date there is no vaccine against leishmaniasis. The current antileishmanial drugs are associated with high resistance and relapse rate. The drugs are highly costly, toxic and have to be administered in hospitals hence not freely accessible to Leishmania infected populations. Prosopis juliflora (PJ) is a locally available plant and has been tested and shown to be effective against helminthes, bacterial diseases and fungal diseases. However, no study has been done to evaluate the antileishmanial effect of PJ methanolic leaf extract. This research was therefore, aimed at testing the leishmanicidal activity and toxicity of PJ leaf extract in BALB/c mice and in in vitro test systems respectively. BALB/c mice of mixed sexes aged between 6 and 8 weeks were used for this study in groups of 8 mice each. For determination of effects of test compounds in a murine model of visceral leishmaniasis, mice were infected intraperitoneally with 2x 106 virulent Leishmania donovani parasites and observed for five weeks for disease establishment. Treatment with the plant extract was done from week 6 and involved daily oral administering by use of gavage needle while Sodium stibogluconate (SSG) for reference drug group and normal saline for infected non-treated mice group were injected intraperitoneally for 21 consecutive days. Weight changes were observed and recorded once weekly during the treatment period. Parasite load was determined by counting parasites in splenic impression smears while antileishmanial IgG antibodies were quantified from serum samples. Parasite burden data was expressed as the mean per 1000 cell nuclei of spleen cells± standard deviation. The data were subjected to One-Way Analysis of Variance (ANOVA) and Tukey post hoc test was used where applicable. A value (p<0.05) was considered significant. The in vitro test of the antileishmanial activity of the methanolic leaf extract of PJ exhibited significant (p<0.05) inhibition of L. donovani promastigotes. There was significant inhibitory effect exhibited by PJ leaf extract on promastigote growth during the in vitro test whereby up to 98 percent parasites were killed at the highest concentrations of the extract as compared to SSG which showed less inhibitory effect on the promastigotes. Both test compounds had significant (p≤ 0.05) effect on the promastigote parasite burden. The splenic amastigote counts after 21 days of administration of both PJ leaf extract and SSG showed significant reduction in the number of amastigotes in the spleen in mice treated with PJ as compared to the SSG treated group hence PJ leaf extract is a suitable candidate in development of a safe antileishmanial compound owing to its safety and efficacy. Prosopis juliflora methanolic leaf extract induced a higher total IgG level as compared to the reference drug which could be attributed to higher titre in IgG2a subtype in mice treated with the extract which was not induced in mice treated with SSG. The findings of this study conclude that PJ exhibited higher inhibitory effects against L. donovani promastigoes as well as amastigotes and induced significantly higher IgG antibody levels as compared to SSG (p<0.05). Furthermore, PJ was safer than SSG on Vero E6 cells. This study therefore, recommends that PJ leaf extract has a high potential for use as an antileishmanial agent and can be evaluated further in non human primate models before application in the treatment of clinical visceral leishmaniasis.
Description
A Thesis Submitted in Partial Fulfillment of the Requirements for the Award of the Degree of Master of Science (Applied Parasitology) in the School of Pure and Applied Sciences of Kenyatta University. March, 2020
Keywords
Safety, Efficacy, Prosopis Juliflora, Leaf Extract, Potential Treatment, Visceral Leishmaniasis