Evaluation of leishmanicidal activity and cytotoxicity of Ricinus communis and Azadirachta indica extracts from western Kenya: in vitro and in vivo assays

Abstract

Background: Despite advances to targeted leishmanicidal chemotherapy, defies around severe toxicity, recent emergence of resistant variants and absence of rational vaccine still persist. This necessitates search and/or progres‑ sive validation of accessible medicinal remedies including plant based. The study examined both in vivo and in vitro response of L. major infection to combined therapy of Ricinus communis and Azadirachta indica extracts in BALB/c mice as the mouse model. A comparative study design was applied. Results: BALB/c mice, treated with combination therapy resulted in significantly (p < 0.05) larger reduction of lesion than those treated with monotherapies. The spleno-somatic index was found to be significantly low with combina‑ tion therapy than monotherapies. Antiparasitic effect of A. indica and R. communis on amastigote with a 50 % inhibi‑ tory concentration (IC50) was of 11.5 and 16.5 µg mL−1 respectively while combination therapy gave 9.0 µg ml−1 compared to the standard drugs, Pentostam and amphotericin B which had an IC50 of 6.5 and 4.5 µg ml−1 respec‑ tively. Optimal efficacy of A. indica and R. communis was 72 and 59.5 % respectively, combination therapy gave 88 %, while Pentostam and amphotericin B had 98 and 92 % respectively against amastigotes. Against promastigotes A. indica and R. Communis gave an IC50 of 10.1, 25.5 µg mL−1 respectively, while combination, 12.2 µg mL−1 against 4.1 and 5.0 µg ml−1 for Pentostam and amphotericin B respectively. The optimal efficacy of the compounds against promastigotes was 78.0, 61.5 and 91.2 % (A. indica, R. communis and A. indica + R. communis respectively) against 96.5 and 98 % for Pentostam and amphotericin B respectively. The concentrations at optimal efficacy were significantly different (p < 0.05) among the test compounds. An evaluation of the IC50 values of the combination therapies clearly reveals synergistic effects. Conclusion: Combination therapy of A. indica and R. communis had best antileishmanial activity than the monother‑ apies. The active ingredients of both R. communis and A. indica need to be fractionated, and studied further for activity against Leishmania parasites.