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Apoptosis mediated leishmanicidal activity of Azadirachta indica bioactive fractions is accompanied by Th1 immunostimulatory potential and therapeutic cure in vivo

Overview of attention for article published in Parasites & Vectors, March 2015
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Title
Apoptosis mediated leishmanicidal activity of Azadirachta indica bioactive fractions is accompanied by Th1 immunostimulatory potential and therapeutic cure in vivo
Published in
Parasites & Vectors, March 2015
DOI 10.1186/s13071-015-0788-3
Pubmed ID
Authors

Garima Chouhan, Mohammad Islamuddin, Muzamil Y Want, Malik Z Abdin, Hani A Ozbak, Hassan A Hemeg, Dinkar Sahal, Farhat Afrin

Abstract

Exploration of immunomodulatory antileishmanials of plant origin is now being strongly recommended to overcome the immune suppression evident during visceral leishmaniasis (VL) and high cost and toxicity associated with conventional chemotherapeutics. In accordance, we assessed the in vitro and in vivo antileishmanial and immunomodulatory potential of ethanolic fractions of Azadirachta indica leaves (ALE) and seeds (ASE). A. indica fractions were prepared by sequential extraction of the powdered plant parts in hexane, ethanol and water. Erythrosin B staining was employed to appraise the anti-promastigote potential of ALE and ASE. Cytostatic or cytocidal mode of action was ascertained and alterations in parasite morphology were depicted under oil immersion light microscopy. Study of apoptotic correlates was performed to deduce the mechanism of induced cell death and anti-amastigote potential was assessed in Leishmania parasitized RAW 264.7 macrophages. In vivo antileishmanial effectiveness was evaluated in L. donovani infected BALB/c mice, accompanied by investigation of immunomodulatory potential of ALE and ASE. Adverse toxicity of the bioactive fractions against RAW macrophages was studied by MTT assay. In vivo side effects on the liver and kidney functions were also determined. Plant secondary metabolites present in ALE and ASE were analysed by Gas chromatography-mass spectrometry (GC-MS). ALE and ASE (500 μg ml(-1)) exhibited leishmanicidal activity in a time- and dose-dependent manner (IC50 34 and 77.66 μg ml(-1), respectively) with alterations in promastigote morphology and induction of apoptosis. ALE and ASE exerted appreciable anti-amastigote potency (IC50 17.66 and 24.66 μg ml(-1), respectively) that was coupled with profound in vivo therapeutic efficacy (87.76% and 85.54% protection in liver and 85.55% and 83.62% in spleen, respectively). ALE exhibited minimal toxicity with selectivity index of 26.10 whereas ASE was observed to be non-toxic. The bioactive fractions revealed no hepato- and nephro-toxicity. ALE and ASE potentiated Th1-biased cell-mediated immunity along with upregulation of INF-γ, TNF-α and IL-2 and decline in IL-4 and IL-10 levels. GC-MS analysis revealed several compounds that may have contributed to the observed antileishmanial effect. Dual antileishmanial and immunostimulatory efficacy exhibited by the bioactive fractions merits their use alone or as adjunct therapy for VL.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 40 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Indonesia 1 3%
Unknown 39 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 18%
Student > Master 5 13%
Student > Postgraduate 4 10%
Researcher 4 10%
Student > Bachelor 4 10%
Other 7 18%
Unknown 9 23%
Readers by discipline Count As %
Agricultural and Biological Sciences 8 20%
Immunology and Microbiology 5 13%
Biochemistry, Genetics and Molecular Biology 4 10%
Chemistry 3 8%
Pharmacology, Toxicology and Pharmaceutical Science 3 8%
Other 7 18%
Unknown 10 25%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 January 2016.
All research outputs
#5,920,325
of 6,908,690 outputs
Outputs from Parasites & Vectors
#1,599
of 1,872 outputs
Outputs of similar age
#245,405
of 301,592 outputs
Outputs of similar age from Parasites & Vectors
#132
of 153 outputs
Altmetric has tracked 6,908,690 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,872 research outputs from this source. They receive a mean Attention Score of 3.6. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 153 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.