title: 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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biological Science (Parasitology), University of Eldoret, P.O Box 1125-30100, Eldoret, Kenya. benjumba@yahoo.co.uk.|Applied Science Department, Sigalagala National Polytechnic, P. O. Box 2966, Kakamega, Kenya. benjumba@yahoo.co.uk.|Department of Medical Laboratory Sciences, Masinde Muliro University of Science and Technology, P.O Box 190, Kakamega, 50100, Kenya. benjumba@yahoo.co.uk.
authors.forename: Bernard N
authors.initials: BN
authors.lastname: Jumba
authors.affiliation: Centre for Biotechnology Research and Development (CBRD), Kenya Medical Research Institute (KEMRI), P.O Box 54840-00200, Nairobi, Kenya. canjili@kemri.org.
authors.forename: Christopher O
authors.initials: CO
authors.lastname: Anjili
authors.affiliation: Department of Biological Science (Parasitology), University of Eldoret, P.O Box 1125-30100, Eldoret, Kenya. jmakwali@yahoo.com.
authors.forename: Judith
authors.initials: J
authors.lastname: Makwali
authors.affiliation: Centre for Biotechnology Research and Development (CBRD), Kenya Medical Research Institute (KEMRI), P.O Box 54840-00200, Nairobi, Kenya. jjingonga@yahoo.co.uk.
authors.forename: Johnstone
authors.initials: J
authors.lastname: Ingonga
authors.affiliation: Zoology Department, Jomo Kenyatta University of Agriculture and Technology (JKUAT), P.O. Box 62000-00200, Nairobi, Kenya. nyamaorose2010@gmail.com.
authors.forename: Rose
authors.initials: R
authors.lastname: Nyamao
authors.affiliation: Department of Biological Science (Parasitology), University of Eldoret, P.O Box 1125-30100, Eldoret, Kenya. marangosylvia@yahoo.com.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Marango
authors.affiliation: University of Kabianga, P.O. Box 2030-20200, Kericho, Kenya. chogekjoseph@gmail.com.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Choge
authors.affiliation: Centre for Biotechnology Research and Development (CBRD), Kenya Medical Research Institute (KEMRI), P.O Box 54840-00200, Nairobi, Kenya. christorwan@gmail.com.|Institute of Tropical Medicine and Infectious Diseases-KEMRI (ITROMID-KEMRI), Jomo Kenyatta University of Agriculture and Technology (JKUAT), P.O. Box 62000-00200, Nairobi, Kenya. christorwan@gmail.com.|African Population and Health Research Center (APHRC), P.O. Box 10787-00100, Nairobi, Kenya. christorwan@gmail.com.
authors.forename: Christopher
authors.initials: C
authors.lastname: Khayeka-Wandabwa
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D031601:Azadirachta / Q000737:chemistry*; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006790:Host-Parasite Interactions / Q000187:drug effects; D020128:Inhibitory Concentration 50; D018320:Leishmania major / Q000187:drug effects* / Q000502:physiology; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D012278:Ricinus / Q000737:chemistry*; D013154:Spleen / Q000187:drug effects / Q000469:parasitology / Q000473:pathology; D014709:Vero Cells
chemical_list: D000981:Antiprotozoal Agents; D010936:Plant Extracts; D009569:Nitric Oxide