肯尼亚西部蓖麻和印楝提取物的杀利什曼原虫活性及细胞毒性评估：体内外试验

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

作者信息

Jumba Bernard N, Anjili Christopher O, Makwali Judith, Ingonga Johnstone, Nyamao Rose, Marango Sylvia, Choge Joseph K, Khayeka-Wandabwa Christopher

机构信息

Department of Biological Science (Parasitology), University of Eldoret, P.O Box 1125-30100, Eldoret, Kenya.

Applied Science Department, Sigalagala National Polytechnic, P. O. Box 2966, Kakamega, Kenya.

出版信息

BMC Res Notes. 2015 Nov 5;8:650. doi: 10.1186/s13104-015-1605-y.

DOI:10.1186/s13104-015-1605-y

PMID:26541197

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4635543/

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 progressive 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 combination therapy than monotherapies. Antiparasitic effect of A. indica and R. communis on amastigote with a 50 % inhibitory 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) respectively. 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 monotherapies. The active ingredients of both R. communis and A. indica need to be fractionated, and studied further for activity against Leishmania parasites.

摘要

背景

尽管针对利什曼原虫的化疗取得了进展，但仍存在严重毒性、耐药变体的出现以及缺乏合理疫苗等问题。这就需要寻找和/或逐步验证包括植物来源在内的可及药物疗法。本研究以BALB/c小鼠为模型，检测了大劣按蚊感染对蓖麻和印楝提取物联合治疗的体内和体外反应。采用了比较研究设计。

结果

联合治疗的BALB/c小鼠病变减少幅度显著大于单药治疗的小鼠（p < 0.05）。联合治疗的脾体指数显著低于单药治疗。印楝和蓖麻对无鞭毛体的抗寄生虫作用，其50%抑制浓度（IC50）分别为11.5和16.5 μg mL⁻¹，而联合治疗为9.0 μg mL⁻¹，相比之下，标准药物喷他脒和两性霉素B的IC50分别为6.5和4.5 μg mL⁻¹。印楝和蓖麻的最佳疗效分别为72%和59.5%，联合治疗为88%，而喷他脒和两性霉素B对无鞭毛体的疗效分别为98%和92%。针对前鞭毛体，印楝和蓖麻的IC50分别为10.1、25.5 μg mL⁻¹，联合治疗为12.2 μg mL⁻¹，而喷他脒和两性霉素B分别为4.1和5.0 μg mL⁻¹。这些化合物对前鞭毛体的最佳疗效分别为78.0%、61.5%和91.2%（分别为印楝、蓖麻和印楝+蓖麻），而喷他脒和两性霉素B分别为96.5%和98%。各受试化合物在最佳疗效时的浓度差异显著（p < 0.05）。对联合治疗IC50值的评估清楚地显示出协同作用。