Jalaja Veronica | University of Hyderabad (original) (raw)
Uploads
Papers by Jalaja Veronica
Current bioactive compounds, Jan 24, 2024
The FEBS Journal, 2019
The emergence of drug-resistant Leishmania is the major challenge to management of visceral leish... more The emergence of drug-resistant Leishmania is the major challenge to management of visceral leishmaniasis (VL) in areas in which this parasite is endemic. Miltefosine has been widely used against VL, but the emergence of resistant strains could impose a significant threat in the near future. The present study used high-throughput proteomics to determine whether proteins are differentially expressed in miltefosine-resistant (BHU875) andsensitive (DD8) L. donovani strains. Comparative proteomic analysis revealed up-regulation of iron superoxide dismutase (FeSODA) in the resistant BHU875 strain compared to the drug-sensitive DD8 strain. In accordance with the proteomic data, BHU875 showed higher FeSODA enzymatic activity relative to the sensitive strain. Molecular characterization of BHU875 parasites in which the gene encoding FeSODA was silenced demonstrated that drug sensitivity was restored and the intracellular survival of the parasite was lowered. This suggests that FeSODA activity plays a part in miltefosine resistance. Our study provides a drug target that could be used to overcome miltefosine resistance or help in rational redesigning of miltefosine-based therapy to combat Leishmania infection.
Scientific reports, Jan 7, 2017
Visceral leishmaniasis (VL) is responsible for several deaths in malnourished children accompanie... more Visceral leishmaniasis (VL) is responsible for several deaths in malnourished children accompanied by diminished circulating leptin and impaired cell-mediated immunity. Typically, leptin deficiency is associated with the Th2 polarization that markedly coincides with the pathogenesis of VL. The aim of the present study was to unravel the prophylactic role of leptin in malnutrition-coupled VL mice. Interestingly, we observed that L. donovani infection itself reduces the serum leptin levels in malnutrition. Exogenous leptin restored severe body weight loss and parasite load in the spleen and liver of malnourished infected mice compared to controls. Leptin increases functional CD8+ T-cell population, Granzyme-A expression down-regulates anergic T-cell markers such as PD-1 and CTLA-4. It was also noticed that, leptin suppresses GM-CSF mRNA expression in parasite favored monocytes and reduced arginase activity in bone marrow derived macrophage indicate macrophages dependent T-cell activat...
Frontiers in medicine, 2017
Visceral leishmaniasis (VL) causes fatal life-threatening disease, if left untreated. The current... more Visceral leishmaniasis (VL) causes fatal life-threatening disease, if left untreated. The current drugs have various limitations; hence, natural products from medicinal plants are being focused in search of new drugs to treat leishmaniasis. The aim of the present study was to evaluate the antileishmanial and immunomodulatory activities of F5 and F6 alcoholic fractions from Withania somnifera leaves and purified withaferin-A in Leishmania donovani-infected peritoneal macrophages and BALB/c mice. We observed that F5 (15 µg/mL), F6 (10 µg/mL), and withaferin-A (1.5 µM) reduce amastigote count in peritoneal macrophages and induce reactive oxygen species and significant decrease in IL-10 mRNA expression compared to control upon treatment. Subsequently, in vivo study mice were treated with F5 (25 and 50 mg/kg b.wt.), F6 (25 and 50 mg/kg b.wt.) orally, and withaferin-A (2 mg/kg b.wt.) intraperitoneally for 10 consecutive days and a drastic reduction in parasite burden in both spleen and li...
Experimental Parasitology, 2016
Leptin induces L. donovani parasite uptake by macrophages of both THP-1 and PBMCs. Leptin upregul... more Leptin induces L. donovani parasite uptake by macrophages of both THP-1 and PBMCs. Leptin upregulates the reactive oxygen species generation in infected THP-1. Leptin enhances the phosphorylation of Akt and Erk1/2 signaling in infected THP-1. Leptin enhances the proinflammatory cytokine response against L. donovani infection in both THP-1 and PBMCs.
Journal of enzyme inhibition and medicinal chemistry, Jan 25, 2015
Withaferin A is an abundant withanolide present in Withania somnifera leaves and to some extent i... more Withaferin A is an abundant withanolide present in Withania somnifera leaves and to some extent in roots. It has been known for its profound anti-cancer properties, but its role in counteracting the Leishmania donovani infection has to be explored. Pteridine reductase 1 (PTR1) is involved in pteridine salvage and an important enzyme for the parasite growth, which could be targeted for the development of an efficient antileishmanial drug. We employed molecular docking studies to identify the binding mode of withaferin A with PTR1 in silico. We further cloned, expressed, and purified PTR1 of L. donovani and performed the enzyme kinetics using the Michaelis-Menten equation and enzyme inhibition studies with withaferin A by plotting the Lineweaver-Burk graph, which followed an uncompetitive mode of inhibition. We also showed the inhibition of the enzyme in the crude lysate of treated parasites. Thus, our study contributes towards understanding the mode of action of withaferin A against ...
Experimental parasitology, Jan 3, 2015
The toxicity and emergence of resistance to available chemical drugs against visceral leishmanias... more The toxicity and emergence of resistance to available chemical drugs against visceral leishmaniasis is evoking to explore herbal treatment. One such attempt with the Neem is being reported here. The current study is primarily focused to evaluate the anti-leishmanial effects of Neem leaf extracts. Among which, ethyl acetate fraction (EAF) alone was found to exhibit leishmanicidal effect validated through cytotoxicity assay and estimated its IC50 to be 52.4 µg/ml on the promastigote stage. Propidium iodide (PI) staining of dead cells substantiated the aforementioned activity. Carboxy fluorescein-diaceate succinimidyl ester (CFSE) staining of promastigotes has affirmed its anti-proliferation activity. The characteristic features such as DNA fragmentation, reduced mitochondrial membrane potential, increased sub G0/G1 phase parasites and increased reactive oxygen species (ROS) production in EAF treated promastigotes indicate the apoptosis like death. In addition, the reduced parasite bur...
Parasitology International, 2013
The aim of this study was to isolate and evaluate the withanolides in inducing apoptotic like dea... more The aim of this study was to isolate and evaluate the withanolides in inducing apoptotic like death in Leishmania donovani in vitro. Withanolides were fractionated and isolated from the leaves of Withania somnifera and LC-MS/MS analysis of two fractions namely, F5 and F6 of ethanolic extracts, obtained through column chromatography with silica gel, was performed. The antileishmanial effect of withanolides on L. donovani promastigotes was assessed in vitro using PI dye exclusion test. The effect of withanolides on promastigote morphology was determined by scanning electron microscopy. To understand their mode of action against L. donovani, DNA fragmentation, quantification of parasites at sub G 0 /G 1 phase, determination of phosphatidylserine externalization, measurement of reactive oxygen species (ROS) and mitochondrial membrane potential (Ψ m) were done. Results showed that LC-MS/MS analysis confirmed the presence of withanolides in isolated fractions. Treatment with withanolides resulted in morphological alterations from spindle to round shape and loss of flagella/cell integrity in promastigotes. Moreover, it induced DNA nicks, cell cycle arrest at sub G 0 /G 1 phase and externalization of phosphatidylserine in dose and time dependent manner via increase in ROS and decrease in Ψ m. Results of this study indicate that withanolides induce apoptotic like death through the production of ROS from mitochondria and disruption of Ψ m in promastigotes of L donovani.
Medical Hypotheses, 2011
Human visceral leishmaniasis (VL) is frequently found in poor population who are suffering from m... more Human visceral leishmaniasis (VL) is frequently found in poor population who are suffering from malnutrition in endemic areas. Therefore, obviously they may have reduced levels of leptin due to reduction in number of adipocytes which are major source of leptin production. Human pathogenesis of VL and reduced levels of leptin both are associated with increase in Th2 type immune response, characterized by secretion of cytokines such as IL-4 and IL-10. Whereas, the protective immune response during visceral leishmaniasis is associated with effective Th1 type immune response characterized by secretion of IFN-c, IL-2 and IL-12, which correlates with leptin induction of T cells polarizing to Th1 population and secretion of proinflammatory cytokines, and also inhibition of Th2 type response. Therefore, we hypothesized that leptin might be effective in treatment of visceral leishmaniasis alone or VL patients who have co-infection with other immune deficiency syndromes such as AIDS/diabetes/autoimmune disorders by regulation of Th1/Th2 homeostasis.
Experimental Parasitology, 2012
h i g h l i g h t s " FCM is a non-flourimetric tool to study stage differentiation in Leishmania... more h i g h l i g h t s " FCM is a non-flourimetric tool to study stage differentiation in Leishmania donovani. " FCM was validated using different molecular and enzymatic assays. " Partial CDS sequence (472 bp) of amastin gene was submitted in GenBank (HQ840734). " Successful differentiation and propagation of LEM 138 were established.
Current bioactive compounds, Jan 24, 2024
The FEBS Journal, 2019
The emergence of drug-resistant Leishmania is the major challenge to management of visceral leish... more The emergence of drug-resistant Leishmania is the major challenge to management of visceral leishmaniasis (VL) in areas in which this parasite is endemic. Miltefosine has been widely used against VL, but the emergence of resistant strains could impose a significant threat in the near future. The present study used high-throughput proteomics to determine whether proteins are differentially expressed in miltefosine-resistant (BHU875) andsensitive (DD8) L. donovani strains. Comparative proteomic analysis revealed up-regulation of iron superoxide dismutase (FeSODA) in the resistant BHU875 strain compared to the drug-sensitive DD8 strain. In accordance with the proteomic data, BHU875 showed higher FeSODA enzymatic activity relative to the sensitive strain. Molecular characterization of BHU875 parasites in which the gene encoding FeSODA was silenced demonstrated that drug sensitivity was restored and the intracellular survival of the parasite was lowered. This suggests that FeSODA activity plays a part in miltefosine resistance. Our study provides a drug target that could be used to overcome miltefosine resistance or help in rational redesigning of miltefosine-based therapy to combat Leishmania infection.
Scientific reports, Jan 7, 2017
Visceral leishmaniasis (VL) is responsible for several deaths in malnourished children accompanie... more Visceral leishmaniasis (VL) is responsible for several deaths in malnourished children accompanied by diminished circulating leptin and impaired cell-mediated immunity. Typically, leptin deficiency is associated with the Th2 polarization that markedly coincides with the pathogenesis of VL. The aim of the present study was to unravel the prophylactic role of leptin in malnutrition-coupled VL mice. Interestingly, we observed that L. donovani infection itself reduces the serum leptin levels in malnutrition. Exogenous leptin restored severe body weight loss and parasite load in the spleen and liver of malnourished infected mice compared to controls. Leptin increases functional CD8+ T-cell population, Granzyme-A expression down-regulates anergic T-cell markers such as PD-1 and CTLA-4. It was also noticed that, leptin suppresses GM-CSF mRNA expression in parasite favored monocytes and reduced arginase activity in bone marrow derived macrophage indicate macrophages dependent T-cell activat...
Frontiers in medicine, 2017
Visceral leishmaniasis (VL) causes fatal life-threatening disease, if left untreated. The current... more Visceral leishmaniasis (VL) causes fatal life-threatening disease, if left untreated. The current drugs have various limitations; hence, natural products from medicinal plants are being focused in search of new drugs to treat leishmaniasis. The aim of the present study was to evaluate the antileishmanial and immunomodulatory activities of F5 and F6 alcoholic fractions from Withania somnifera leaves and purified withaferin-A in Leishmania donovani-infected peritoneal macrophages and BALB/c mice. We observed that F5 (15 µg/mL), F6 (10 µg/mL), and withaferin-A (1.5 µM) reduce amastigote count in peritoneal macrophages and induce reactive oxygen species and significant decrease in IL-10 mRNA expression compared to control upon treatment. Subsequently, in vivo study mice were treated with F5 (25 and 50 mg/kg b.wt.), F6 (25 and 50 mg/kg b.wt.) orally, and withaferin-A (2 mg/kg b.wt.) intraperitoneally for 10 consecutive days and a drastic reduction in parasite burden in both spleen and li...
Experimental Parasitology, 2016
Leptin induces L. donovani parasite uptake by macrophages of both THP-1 and PBMCs. Leptin upregul... more Leptin induces L. donovani parasite uptake by macrophages of both THP-1 and PBMCs. Leptin upregulates the reactive oxygen species generation in infected THP-1. Leptin enhances the phosphorylation of Akt and Erk1/2 signaling in infected THP-1. Leptin enhances the proinflammatory cytokine response against L. donovani infection in both THP-1 and PBMCs.
Journal of enzyme inhibition and medicinal chemistry, Jan 25, 2015
Withaferin A is an abundant withanolide present in Withania somnifera leaves and to some extent i... more Withaferin A is an abundant withanolide present in Withania somnifera leaves and to some extent in roots. It has been known for its profound anti-cancer properties, but its role in counteracting the Leishmania donovani infection has to be explored. Pteridine reductase 1 (PTR1) is involved in pteridine salvage and an important enzyme for the parasite growth, which could be targeted for the development of an efficient antileishmanial drug. We employed molecular docking studies to identify the binding mode of withaferin A with PTR1 in silico. We further cloned, expressed, and purified PTR1 of L. donovani and performed the enzyme kinetics using the Michaelis-Menten equation and enzyme inhibition studies with withaferin A by plotting the Lineweaver-Burk graph, which followed an uncompetitive mode of inhibition. We also showed the inhibition of the enzyme in the crude lysate of treated parasites. Thus, our study contributes towards understanding the mode of action of withaferin A against ...
Experimental parasitology, Jan 3, 2015
The toxicity and emergence of resistance to available chemical drugs against visceral leishmanias... more The toxicity and emergence of resistance to available chemical drugs against visceral leishmaniasis is evoking to explore herbal treatment. One such attempt with the Neem is being reported here. The current study is primarily focused to evaluate the anti-leishmanial effects of Neem leaf extracts. Among which, ethyl acetate fraction (EAF) alone was found to exhibit leishmanicidal effect validated through cytotoxicity assay and estimated its IC50 to be 52.4 µg/ml on the promastigote stage. Propidium iodide (PI) staining of dead cells substantiated the aforementioned activity. Carboxy fluorescein-diaceate succinimidyl ester (CFSE) staining of promastigotes has affirmed its anti-proliferation activity. The characteristic features such as DNA fragmentation, reduced mitochondrial membrane potential, increased sub G0/G1 phase parasites and increased reactive oxygen species (ROS) production in EAF treated promastigotes indicate the apoptosis like death. In addition, the reduced parasite bur...
Parasitology International, 2013
The aim of this study was to isolate and evaluate the withanolides in inducing apoptotic like dea... more The aim of this study was to isolate and evaluate the withanolides in inducing apoptotic like death in Leishmania donovani in vitro. Withanolides were fractionated and isolated from the leaves of Withania somnifera and LC-MS/MS analysis of two fractions namely, F5 and F6 of ethanolic extracts, obtained through column chromatography with silica gel, was performed. The antileishmanial effect of withanolides on L. donovani promastigotes was assessed in vitro using PI dye exclusion test. The effect of withanolides on promastigote morphology was determined by scanning electron microscopy. To understand their mode of action against L. donovani, DNA fragmentation, quantification of parasites at sub G 0 /G 1 phase, determination of phosphatidylserine externalization, measurement of reactive oxygen species (ROS) and mitochondrial membrane potential (Ψ m) were done. Results showed that LC-MS/MS analysis confirmed the presence of withanolides in isolated fractions. Treatment with withanolides resulted in morphological alterations from spindle to round shape and loss of flagella/cell integrity in promastigotes. Moreover, it induced DNA nicks, cell cycle arrest at sub G 0 /G 1 phase and externalization of phosphatidylserine in dose and time dependent manner via increase in ROS and decrease in Ψ m. Results of this study indicate that withanolides induce apoptotic like death through the production of ROS from mitochondria and disruption of Ψ m in promastigotes of L donovani.
Medical Hypotheses, 2011
Human visceral leishmaniasis (VL) is frequently found in poor population who are suffering from m... more Human visceral leishmaniasis (VL) is frequently found in poor population who are suffering from malnutrition in endemic areas. Therefore, obviously they may have reduced levels of leptin due to reduction in number of adipocytes which are major source of leptin production. Human pathogenesis of VL and reduced levels of leptin both are associated with increase in Th2 type immune response, characterized by secretion of cytokines such as IL-4 and IL-10. Whereas, the protective immune response during visceral leishmaniasis is associated with effective Th1 type immune response characterized by secretion of IFN-c, IL-2 and IL-12, which correlates with leptin induction of T cells polarizing to Th1 population and secretion of proinflammatory cytokines, and also inhibition of Th2 type response. Therefore, we hypothesized that leptin might be effective in treatment of visceral leishmaniasis alone or VL patients who have co-infection with other immune deficiency syndromes such as AIDS/diabetes/autoimmune disorders by regulation of Th1/Th2 homeostasis.
Experimental Parasitology, 2012
h i g h l i g h t s " FCM is a non-flourimetric tool to study stage differentiation in Leishmania... more h i g h l i g h t s " FCM is a non-flourimetric tool to study stage differentiation in Leishmania donovani. " FCM was validated using different molecular and enzymatic assays. " Partial CDS sequence (472 bp) of amastin gene was submitted in GenBank (HQ840734). " Successful differentiation and propagation of LEM 138 were established.