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.

Background: The recent treatment challenges posed by the widespread emergence of pathogenic multidrug-resistant (MDR) bacterial strains cause huge health problems worldwide. Infections caused by MDR organisms are associated with longer periods of hospitalization, increased mortality, and inflated healthcare costs. Staphylococcus aureus is one of these MDR organisms identified as an urgent threat to human health by the World Health Organization. Infections caused by S. aureus may range from simple cutaneous infestations to life-threatening bacteremia. S. aureus infections easily escalate in severely ill, hospitalized, and or immunocompromised patients with an incapacitated immune system. Also, in HIV-positive patients, S. aureus ranks amongst one of the most common comorbidities where it can further worsen a patient’s health condition. At present, anti-staphylococcal therapy is typically reliant on chemotherapeutics that are gaining resistance and pose unfavorable side-effects. Thus, newer drugs are required that can bridge these shortcomings and aid effective control against S. aureus. Objective: In this review, we summarize drug resistance exhibited by S. aureus, lacunae in current anti-staphylococcal therapy and nanoparticles as an alternative therapeutic modality. The focus lies on various green synthesized nanoparticles, their mode of action, and their application as potent antibacterial compounds against S. aureus. Conclusion: The use of nanoparticles as anti-bacterial drugs has gained momentum in the recent past, and green synthesized nanoparticles, which involve microorganisms and plants or their byproducts for the synthesis of nanoparticles, offer a potent, as well as environment friendly solution in warfare against MDR bacteria.