The Experts below are selected from a list of 987 Experts worldwide ranked by ideXlab platform

Santi Sinha P Babu - One of the best experts on this subject based on the ideXlab platform.

  • Antifilarial activity of azadirachtin fuelled through reactive oxygen species induced apoptosis a thorough molecular study on setaria cervi
    Journal of Helminthology, 2019
    Co-Authors: Niladri Mukherjee, Nikhilesh Joardar, Santi Sinha P Babu
    Abstract:

    Efficacious therapeutic strategies against lymphatic filariasis are always sought after. However, natural products are a promising resource for developing effective Antifilarial agents. Azadirachtin, a significant tetranortriterpenoid phytocompound found in Azadirachta indica, was evaluated in vitro for Antifilarial potential against the filarial parasite Setaria cervi. Dye exclusion and MTT assay confirmed the Antifilarial potential of azadirachtin against S. cervi with a median lethal dose (LC50) of 6.28 μg/ml for microfilariae (mf), and 9.55 μg/ml for adult parasites. Morphological aberrations were prominent in the histological sections of the azadirachtin-exposed parasites. Moreover, alterations in the reactive oxygen species (ROS) parameters in treated parasites were evident. Induction of apoptosis in treated parasites was confirmed by DNA laddering, acridine orange (AO)/ethidium bromide (EtBr) double staining and in situ DNA fragmentation. The downregulation of anti-apoptotic CED-9 and upregulation of proapoptotic EGL-1, CED-4 and CED-3 at both the transcription and translation levels confirmed apoptosis execution at the molecular level. Changes in the gene expressions of nuc-1, cps-6 and crn-1 further clarified the molecular cause of DNA degradation. Furthermore, azadirachtin was found to be non-toxic in both in vitro and in vivo toxicity analyses. Therefore, the experimental evidence detailed the pharmacological effectiveness of azadirachtin as a possible therapeutic agent against filariasis.

  • polyphenol enriched ethanolic extract of cajanus scarabaeoides l thouars exerts potential Antifilarial activity by inducing oxidative stress and programmed cell death
    PLOS ONE, 2018
    Co-Authors: Anindya Sundar Ray, Suprabhat Mukherjee, Nikhilesh Joardar, Chowdhury Habibur Rahaman, Santi Sinha P Babu
    Abstract:

    Development of Antifilarial drug from the natural sources is considered as one of the most efficacious, safe, and affordable approaches. In this study, we report the Antifilarial activity of a leguminous plant Cajanus scarabaeoides (L.) Thouars. The polyphenol-rich ethanolic extract obtained from the stem part of the plant C. scarabaeoides (EECs) was found to be efficient in killing the filarial nematode Setaria cervi in all the three developmental stages viz. oocytes, microfilariae (Mf) and adults with LD50 values of 2.5, 10 and 35 μg/ml, respectively. While studying the molecular mechanism of action, we found that induction of oxidative stress plays the key role in inducing the mortality in S. cervi. The redox imbalance finally results in activation of the nematode CED pathway that executes the death of the parasite. Intriguingly, EECs was found to be selectively active against the worm and absolutely non-toxic to the mammalian cells and tissues. Taken together, our experimental data demonstrate that C. scarabaeoides can be chosen as an affordable natural therapeutic for treating filarial infection in the future with high efficacy and less toxicity.

  • chitosan biopolymer functionalized gold nanoparticles with controlled cytotoxicity and improved Antifilarial efficacy
    Advanced Composites and Hybrid Materials, 2018
    Co-Authors: Pranesh Chowdhury, Suprabhat Mukherjee, Nikhilesh Joardar, Maloy Kr Mondal, Debiprasad Roy, Niladri Mukherjee, Bishnupada Roy, Santi Sinha P Babu
    Abstract:

    Ultra-high stable chitosan functionalized gold nanoparticles (GNPs) of desired biopolymeric corona are synthesized without adding conventional hazardous reducing agents. The inherent unique set of properties like reducing ability, stabilizing effect, and mucoadhesiveness of chitosan is exhibited in the present work. Morphologies and ultra-stability of the synthesized materials are characterized by standard techniques. The mucoadhesiveness of the synthesized materials are well documented through the biological potency of the synthesized GNPs. The prominent bioactivity is evident from the Antifilarial activity. The cellular and molecular level studies on the induction of oxidative stress, DNA damage, and undesirable protein expression clearly explain the Antifilarial activities. Interestingly, the developed nanoparticle shows no detectable sign of toxicity when evaluated in vitro (rat peritoneal MФ) or in vivo (Wistar rat). Therefore, the synthesized green GNPs appear to be a substantial promise as an efficacious broad-spectrum nanotherapeutic agent with safe outcome for clinical attempt.

  • Scheme depicting mechanism of Antifilarial activity of EECs.
    2018
    Co-Authors: Anindya Sundar Ray, Suprabhat Mukherjee, Nikhilesh Joardar, Chowdhury Habibur Rahaman, Santi Sinha P Babu
    Abstract:

    Scheme depicting mechanism of Antifilarial activity of EECs.

  • Evaluation of Antifilarial activity in different solvent extracts (crude) of Cajanus scarabaeoides.
    2018
    Co-Authors: Anindya Sundar Ray, Suprabhat Mukherjee, Nikhilesh Joardar, Chowdhury Habibur Rahaman, Santi Sinha P Babu
    Abstract:

    Evaluation of Antifilarial activity in different solvent extracts (crude) of Cajanus scarabaeoides.

Shailja Misrabhattacharya - One of the best experts on this subject based on the ideXlab platform.

  • resolution absolute configuration and Antifilarial activity of coumarinyl amino alcohols
    Tetrahedron-asymmetry, 2017
    Co-Authors: Sweta Misra, Shailja Misrabhattacharya, Ray J Butcher, Diksha Katiyar
    Abstract:

    Abstract The resolution of racemic coumarinyl amino alcohols 5–10 was achieved by using the inexpensive and readily accessible chiral resolving agent N-carbethoxy- l -proline (S)-11. Direct esterification of rac-5–10 with (S)-11 furnished diastereomeric esters, which were easily separated by column chromatography. The obtained diastereomers yielded the desired enantiopure coumarinyl amino alcohols (S)-(+)-5–10 and (R)-(−)-5–10 in good yields with high enantiomeric excess on saponification. The absolute configurations were determined by X-ray crystal analysis and/or by comparison of the specific rotations. Furthermore, in in vitro Antifilarial motility inhibition assays, enantiopure coumarins (S)-(+)-9, (R)-(−)-9 and (S)-(+)-10, (R)-(−)-10 were found to be less efficient in affecting the viability of macrofilariae of Brugia malayi than their racemic forms 9 and 10, respectively, indicating the synergistic effect of the enantiomers in evoking Antifilarial action.

  • synthesis and biological evaluation of 4 oxycoumarin derivatives as a new class of Antifilarial agents
    European Journal of Medicinal Chemistry, 2015
    Co-Authors: Sweta Misra, Shailja Misrabhattacharya, Jyoti Gupta, L Singh, Diksha Katiyar
    Abstract:

    A series of 4-oxycoumarin derivatives was synthesized, characterized and evaluated in vitro and in vivo for Antifilarial activity against the human lymphatic filarial parasite, Brugia malayi. A majority of the compounds studied showed potent in vitro activity with low IC50 values in the micro molar (μM) range (0.014-1.73 and 0.0056-0.43) against adult worms and microfilariae, respectively. Compounds 8 and 9 were identified to be the most promising Antifilarial candidate molecules exhibiting activity in the nanomolar (nM) range. The IC50 values for compound 8 were 14 nM and 5.6 nM while for compound 9 were 94 nM and 13 nM, respectively, for adult worm and microfilaria. These two compounds also displayed promising adulticidal activity (74.9 ± 4.8% and 69.4 ± 2.8%, respectively) in the primary rodent (jird) screen. This study also serves as a starting point for investigating structure-activity relationship with different amino substituents.

  • improved Antifilarial activity of ivermectin in chitosan alginate nanoparticles against human lymphatic filarial parasite brugia malayi
    Parasitology Research, 2013
    Co-Authors: Mohammad Ali, Shailja Misrabhattacharya, Meenakshi Verma, Mohammad Afzal, Farhan Jalees Ahmad, Amit K Dinda
    Abstract:

    The current Antifilarial treatments are not up to the mark partly due to deep location of filarial parasites in the human lymphatic system. We report here on the improvement in the Antifilarial activity of ivermectin (IVM) using chitosan–alginate nanoparticles prepared by modified complex coacervation method. The nanoparticles were spherical having 155 nm size and 4.56 and 75.67 % loading and entrapment efficiency respectively for IVM. The delivery system maintained the sustained release and significantly augmented the microfilaricidal (MIF) activity at a single low dose (200 μg/kg body weight, subcutaneously) in contrast to much higher dose of free ivermectin (400 μg/kg body weight, subcutaneously) against human lymphatic filariid, Brugia malayi in rodent host, Mastomys coucha. To substantiate increase in MIF activity, pharmacokinetics study was designed on Wistar rats which revealed a greater peak plasma concentration (45.3 ± 1.79 ng/ml), area under the concentration curve (298 ± 38.7 ng d/ml) and extended mean residence time (23.4 ± 8.56 days)of IVM in chitosan–alginate nanoparticles. Administration of 25 mg/kg of diethylcarbamazine following nanoparticle therapy significantly improved the MIF and macrofilaricidal action of encapsulated drug and was considered superior in this study.

  • Antifilarial activity of marine sponge haliclona oculata against experimental brugia malayi infection
    Experimental Parasitology, 2012
    Co-Authors: Jyoti Gupta, Sweta Misra, Shishir Srivastava, Vijai Lakshmi, S K Mishra, Mahendra Nath Srivastava, Shailja Misrabhattacharya
    Abstract:

    Abstract The present study incorporates the findings on in vitro and in vivo Antifilarial activity in the marine sponge, Haliclona oculata using an experimental rodent infection of human lymphatic filarial parasite, Brugia malayi . The in vitro Antifilarial action was determined on both adult female worms as well as microfilariae using two parameters viz. adverse effect on motility and inhibition in MTT reduction by the treated adult parasite over control worm. The Antifilarial activity could be located in the methanol extract and one of its four fractions (chloroform). Bioactivity guided fractionation of chloroform fraction led to localization of in vitro activity in one of its eight chromatographic fractions. Methanol extract, chloroform fraction and one of the chromatographic fractions revealed IC 50 values of 5.00, 1.80, and 1.62 μg/ml, respectively when adult B. malayi were exposed to these test samples for 72 h at 37 °C. Under similar exposure conditions, the IC 50 values for microfilariae were 1.88, 1.72 and 1.19 μg/ml, respectively. The active test samples were found to be safe revealing >10 selectivity indices (SI) on the basis of cytotoxicity to Vero cells (monkey kidney cells) and therefore selected for in vivo evaluation against primary (adult B. malayi intraperitoneal transplanted jird) and secondary (subcutaneous infective larvae induced mastomys) screens. In primary jird model, the three test samples at 100 mg/kg for five consecutive days by subcutaneous route demonstrated significant macrofilaricidal efficacy to the tune of 51.3%, 64% and 70.7% by methanol extract, chloroform and chromatographic fraction, respectively. The three samples demonstrated 45–50% macrofilaricidal activity with moderate embryostatic effect in secondary model at 5 × 500, 5 × 250 and 5 × 125 mg/kg by oral route. Chromatographic fraction possessing highest Antifilarial action was primarily found to be a mixture of four alkaloids Mimosamycin, Xestospongin-C, Xestospongin-D and Araguspongin-C in addition to few minor compounds.

  • rnai mediated silencing of atpase rna helicase gene in adult filarial parasite brugia malayi impairs in vitro microfilaria release and adult parasite viability
    Journal of Biotechnology, 2012
    Co-Authors: Meghna Singh, Prashant Kumar Singh, Shailja Misrabhattacharya
    Abstract:

    The DExD/H box families of RNA helicases are a multifunctional group of proteins involved in unwinding of inter- and intra-molecular base-paired regions. Successful knockdown of DEAD box RNA helicase gene (BmL3-Helicase) of human lymphatic filarial parasite Brugia malayi was done with specifically designed and chemically synthesized siRNA of <20 bp to observe the role of enzyme in parasite biology and its worth as an Antifilarial drug target. We made efforts to deliver siRNA into parasite by both electroporation and soaking that resulted into diminished helicase gene expression associated with decreased parasite motility, viability (97%) and release of microfilariae (81.0% reduction) from adult females in vitro. The specific gene knockdown also resulted into death of adult male worms in addition to phenotypic deformities in female worm intrauterine stages. RT-PCR of siRNA treated worms revealed a complete knockdown of BmL3-Helicase transcription within 16 h. The present findings thus illustrate that targeting helicase gene of B. malayi would not only interfere with embryogenesis and microfilarial production but also result into decreased motility and viability of microfilariae and adult parasites. The B. malayi helicase enzyme thus represents a possible Antifilarial drug target.

P. K. Murthy - One of the best experts on this subject based on the ideXlab platform.

  • Antifilarial diarylheptanoids from alnus nepalensis leaves growing in high altitude areas of uttarakhand india
    Phytomedicine, 2013
    Co-Authors: Deepti Yadav, P. K. Murthy, Richa Verma, K C Saxena, Subhash C Singh, R K Verma, Madan M Gupta
    Abstract:

    Lymphatic filariasis continues to be a major health problem in tropical and subtropical countries. A macrofilaricidal agent capable of eliminating adult filarial parasites is urgently needed. Platyphyllenone (A), alusenone (B), hirustenone (C) and hirsutanonol (D) are important biologically active diarylheptanoids present in Alnus nepalensis. In the present study, we report the Antifilarial activity in diarylheptanoids isolated from the leaves of A. nepalensis. Out of four compounds (A-D) tested in vitro one has shown promising anti-filarial activity both in vitro and in vivo studies. This is the first ever report on Antifilarial efficacy of a compound of the plant and warrants further studies around this scaffold. In addition, a sensitive, selective and robust densitometric high-performance thin-layer chromatographic method was developed and validated for the above four biomarker compounds. The separation was performed on silica gel 60F(254) high-performance thin layer chromatography plates using chloroform:methanol (9:1, v/v) as mobile phase. The quantitation of marker compounds was carried out using densitometric reflection/absorption mode at 600 nm after post-chromatographic derivatization using vanillin-sulfuric acid reagent. The method was validated for peak purity, precision, robustness, limit of detection (LOD) and quantitation (LOQ) etc., as per the International Conference on Harmonization (ICH) guidelines.

  • in vitro and in vivo Antifilarial activity evaluation of 3 6 epoxy 1 5 dioxocines a new class of Antifilarial agents
    Bioorganic & Medicinal Chemistry Letters, 2012
    Co-Authors: Koneni V. Sashidhara, Vikas Kushwaha, K C Saxena, Abdhesh Kumar, Bhaskara K Rao, P. K. Murthy
    Abstract:

    Abstract A series of 3,6-epoxy [1,5]dioxocines were synthesized and evaluated for their Antifilarial activity against adult parasites of human lymphatic filarial parasite Brugia malayi (sub-periodic strain) in vitro. Out of these, six compounds (4a–f) possessed improved in vitro anti-filarial activity and examples 4d and 4f were also found to be active in the in vivo experiments. These results demonstrate that 3,6-epoxy [1,5]dioxocines exhibits potent Antifilarial activity and might be developed into a new class of Antifilarial drug.

  • Antifilarial activity of gum from moringa oleifera lam on human lymphatic filaria brugia malayi
    Chronicles of Young Scientists, 2011
    Co-Authors: Vikas Kushwaha, Vijai Lakshmi, K C Saxena, S K Verma, Rolee Sharma, P. K. Murthy
    Abstract:

    Aim: Currently available Antifilarial drugs diethylcarbamazine, ivermectin and albendazole and their combinations, are not able to control lymphatic filariasis. Therefore, a better Antifilarial agent is urgently required for proper management of the disease. Materials and Methods: In this study, we evaluated the Antifilarial activity of gum extract of plant Moringa oleifera Lam. against the human lymphatic filarial parasite Brugia malayi using adult worms and microfilariae (mf) in two in vitro assays (motility and inhition in MTT reduction) for viability and two animal models, primary (Meriones unguiculatus implanted with B. malayi adult worms in the peritoneal cavity) and secondary (subcutaneous B. malayi infective larvae induced Mastomys coucha, the model closer to the natural human filarial infection) screens. Results: The gum extract inhibited 100% motility (irreversible loss of motility) of mf and inhibited more than 56% MTT reduction potential of the adult female worms. The extract was safe in cytotoxicity test using Vero cell line, therefore followed in vivo in primary and secondary screens. In primary screen, the extract (5×500 mg/kg) caused 69% macrofilaricidal and 83% sterilization of female worms and 44% macrofilaricidal activity in secondary screen (5 × 1000 mg/kg) by oral route. Conclusion: Thus, it is concluded that the gum of the plant is macrofilaricidal in both in vitro and in vivo and may provide valuable leads for design and development of new Antifilarial agents. This is the first ever report on the Antifilarial efficacy of M. oleifera.

  • Antifilarial activity in vitro and in vivo of some flavonoids tested against brugia malayi
    Acta Tropica, 2010
    Co-Authors: Vijai Lakshmi, Malaya K. Sahoo, Sunil Kumar Mishra, Shishir Srivastava, S K Verma, Sujith K Joseph, V Dube, P. K. Murthy
    Abstract:

    We evaluated the Antifilarial activity of 6 flavonoids against the human lymphatic filarial parasite Brugia malayi using an in vitro motility assay with adult worms and microfilariae, a biochemical test for viability (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT)-reduction assay), and two animal models, Meriones unguiculatus (implanted adult worms) and Mastomys coucha (natural infections). In vitro, naringenin and hesperetin killed the adult worms and inhibited (>60%) MTT-reduction at 7.8 and 31.2 μg/ml concentration, respectively. Microfilariae (mf) were killed at 250-500 μg/ml. The half maximal inhibitory concentration (IC(50)) of naringenin for motility of adult females was 2.5 μg/ml. Flavone immobilized female adult worms at 31.2 μg/ml (MTT>80%) and microfilariae at 62.5 μg/ml. Rutin killed microfilariae at 125 μg/ml and inhibited MTT-reduction in female worms for >65% at 500 μg/ml. Naringin had adulticidal effects at 125 μg/ml while chrysin killed microfilariae at 250 μg/ml. In vivo, 50 mg/kg of naringenin elimiated 73% of transplanted adult worms in the Meriones model, but had no effect on the microfilariae in their peritoneal cavity. In Mastomys, the same drug was less effective, killing only 31% of the naturally acquired adult worms, but 51%, when the dose was doubled. Still, effects on the microfilariae in the blood were hardly detectable, even at the highest dose. In summary, all 6 flavonoids showed Antifilarial activity in vitro, which can be classed, in a decreasing order: naringenin>flavone=hesperetin>rutin>naringin>chrysin. In jirds, naringenin and flavone killed or sterilized adult worms at 50mg/kg dose, but in Mastomys, where the parasite produces a patent infection, only naringenin was filaricidal. Thus naringenin and flavone may provide a lead for design and development of new Antifilarial agent(s). This is the first report on Antifilarial efficacy of flavonoids.

  • synthesis of 2 sulfanyl 6 methyl 1 4 dihydropyrimidines as a new class of Antifilarial agents
    European Journal of Medicinal Chemistry, 2008
    Co-Authors: Brajesh K. Singh, Mridul Mishra, Nisha Saxena, Gaya P Yadav, Prakas R Maulik, Rajiv L Gaur, Malaya K. Sahoo, P. K. Murthy, Rama P Tripathi
    Abstract:

    Abstract A series of 2-sulfanyl-6-methyl-1,4-dihydropyrimidines ( 8 – 21 ) were synthesized in good yields by alkylation of 5-methyl-6-phenyl-2-thioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid ethyl esters ( 2 – 7 ) with different alkyl or aralkyl halides in the presence of a combination of anhydrous K 2 CO 3 and catalytic amount of tetrabutyl ammonium bromide. The title compounds were evaluated for their Antifilarial activity against adult parasites of human lymphatic filarial parasite Brugia malayi (sub-periodic strain) in vitro and in vivo at various concentrations. One of the compounds ( 18 ) showed promising Antifilarial activity.

Priya Roy - One of the best experts on this subject based on the ideXlab platform.

  • exploration of Antifilarial activity of gold nanoparticle against human and bovine filarial parasites a nanomedicinal mechanistic approach
    Colloids and Surfaces B: Biointerfaces, 2018
    Co-Authors: Priya Roy, Swadhin K Saha, Pranesh Chowdhury, P K Gayen, Santi Sinha P Babu
    Abstract:

    Abstract The present work seeks to explore the Antifilarial activity of biopolymer functionalized gold nanoparticles (AuNPs) against human filarial parasite (Wuchereria bancrofti) through Nrf2 signaling for the first time. A natural polymer, chitosan is used along with Terminalia chebula extract to synthesize AuNPs following the principles of green chemistry. The probable mode of action of AuNPs as filaricidal agent has been investigated in detail using model filarial parasite, Setaria cervi (bovine parasite). Biopolymers inspired AuNPs exhibit superior Antifilarial activity against both human and bovine filarial parasites, and are able to induce oxidative stress and apoptotic cell death in filarial parasites mediated through mitochondria. AuNPs also alter the Nrf2 signaling. In addition, the synthesized nanomaterials appear to be nontoxic to mammalian system. Thus the present mechanistic study, targeting human filarial parasites, has the potential to increase the therapeutic prospects of AuNPs to control lymphatic filariasis in the upcoming days.

  • development of chitosan based gold nanomaterial as an efficient Antifilarial agent a mechanistic approach
    Carbohydrate Polymers, 2017
    Co-Authors: Swadhin K Saha, Priya Roy, Maloy Kr Mondal, Debiprasad Roy, Prajna Gayen, Pranesh Chowdhury, Santi Sinha P Babu
    Abstract:

    The gold nanoparticles (AuNPs) have been synthesized biogenically by using black pepper (Piper nigrum) extract according to the principles of green chemistry in presence and absence of a biopolymer, chitosan. A comprehensive study (up to cellular level) on the Antifilarial (against Setaria cervi) activity of AuNPs has been made for the first time with a view to use it clinically. The bioactivity of biopolymer capped biogenic AuNP increases significantly compared to simple biogenic AuNP. The biopolymer plays an important role in inspiring AuNP through its inherent positive charges and hydrophobicity. The developed nanomaterial boosts the production of ROS (reactive oxygen species) and misbalances the antioxidant parameters of parasites such as GSH, GST, GPx, SOD and catalase. The produced ROS ultimately induces oxidative stress, which leads to apoptotic cell death in filarial worms. The synthesized nanomaterials exhibit negligible toxicity towards human PBMCs. The present study may serve as a fruitful platform to explore biopolymer capped gold nanoparticles as efficient Antifilarial therapeutics.

  • evidence of reactive oxygen species ros mediated apoptosis in setaria cervi induced by green silver nanoparticles from acacia auriculiformis at a very low dose
    Experimental Parasitology, 2016
    Co-Authors: Prasanta Saini, Swadhin K Saha, Priya Roy, Pranesh Chowdhury, Santi Sinha P Babu
    Abstract:

    Green synthesis of silver nanomaterial plays a pivotal role in the growing field of nanotechnology. Development of anti-parasitic drugs from plant metabolites has been in regular practice from the ancient period but most of them were discarded due to their inefficiency to control diseases effectively. At present, nanoparticles are used for developing anti-parasitic therapy for their unique properties such as smallest in size, bio-ability, bio-compatibility and penetration capacity into a cell. The present study aims at synthesis of silver nanoparticles (AgNPs) by using funicles extract of Acacia auriculiformis and tests its efficacy as Antifilarial. Experimental evidence show that AgNPs are effective at a very low concentration compared to crude plant extracts. Synthesis of these nanoparticles is a single-step, biogenic, cost effective and eco-friendly process. Synthesized nanoparticles were characterized by UV-Vis spectroscopy, TEM, SAED, FTIR, EDX, FESEM and Z-potential. The Antifilarial efficacy of AgNPs was tested against different life cycle stages of bovine filarial parasite Setaria cervi by morphological study, motility assessment and viability assay. These nanoparticles are found to have Antifilarial activity with LC50 of 5.61 μg/mL and LC90 of 15.54 μg/mL against microfilaria of S. cervi. The microscopic findings and the detailed molecular studies confirmed that green synthesized AgNPs were effective enough to induce apoptosis through up regulation of ROS (reactive oxygen species).

  • Antifilarial effects of polyphenol rich ethanolic extract from the leaves of azadirachta indica through molecular and biochemical approaches describing reactive oxygen species ros mediated apoptosis of setaria cervi
    Experimental Parasitology, 2014
    Co-Authors: Niladri Mukherjee, Suprabhat Mukherjee, Priya Roy, Prasanta Saini, Santi Sinha P Babu
    Abstract:

    Abstract Lymphatic filariasis, a global cause of morbidity needs much more attention in developing potent therapeutics that can be effective against both microfilariae (mf) and adults. Efficient botanicals that can induce apoptosis of filarial parasites possibly can provide a direction towards developing new class of Antifilarials. In this work we have evaluated the Antifilarial efficacy of an optimized polyphenol rich ethanolic extract of Azadirachta indica leaves (EEA). A. indica A. Juss has been widely used in the traditional Indian medicinal system ‘Ayurveda’ for the treatment of a variety of ailments. A thorough investigation towards biochemical and molecular mechanisms describing ROS mediated apoptosis in Setaria cervi was performed. Motility reduction, MTT reduction assay and dye exclusion test have confirmed the micro- and macrofilaricidal potential of EEA. Alterations were visible in mf and trichrome stained section of EEA-treated adult worms. We have found cellular disturbances in EEA-treated parasites characterized by chromatin condensation, in situ DNA fragmentation and nucleosomal DNA laddering. Depletion in worm GSH level and elevation in parasite GST, SOD, catalase, GPx and superoxide anion indicated the generation of ROS. Our results provided experimental evidence supporting that EEA causes a decreased expression of anti-apoptotic genes and increased pro-apoptotic gene expression at the level of both transcription and translation. Here we are reporting for the first time that Antifilarial activity of EEA is mediated by ROS up regulation and apoptosis.

Patrick J. Lammie - One of the best experts on this subject based on the ideXlab platform.

  • Longitudinal Monitoring of the Development of Antifilarial Antibodies and Acquisition of Wuchereria bancrofti in a Highly Endemic Area of Haiti
    2016
    Co-Authors: Katy L Hamlin, Mark L. Eberhard, Thomas B. Nutman, Thomas G Streit, Joseph Kubofcik, Delynn M Moss, Jeffrey W Priest, Katherine Gass, Jacquelin Roberts, Patrick J. Lammie
    Abstract:

    Antifilarial antibody testing has been established as a sensitive and specific method of diagnosing lymphatic filariasis. However, the development of serological responses to specific filarial antigens and their relationship to acquisition of infection is poorly understood. In order to evaluate whether the development of antigen specific Antifilarial antibodies precedes microfilaremia and antigenemia, we compared the antibody responses of serum samples collected between 1990 and 1999 from a cohort of 142 Haitian children followed longitudinally. Antigen status was determined using the Og4C3 ELISA and the presence of microfilaremia was detected using microscopy. Antibody responses to Wb123, a Wuchereria bancrofti L3 antigen, were measured using a Luciferase Immunoprecipitation System (LIPS) assay. Antibody responses to Bm14 and Bm33, Brugia malayi antigens and to a major surface protein (WSP) from Wolbachia were analyzed using a multiplex bead assay. Over follow-up, 80 (56%) of the children became antigen-positive and 30 (21%) developed microfilaremia. Detectable antibody responses to Bm14, Bm33, Wb123, and WSP developed in 95%, 100%, 92%, and 29 % of children, respectively. With the exception of WSP, the development of antibody responses generally preceded detection of filarial antigen. Our results show that Antifilarial antibody responses can serve as an important epidemiological indicator in a sentinel population of young children and thus, may be valuable as tool for surveillance in the context of lymphatic filariasi

  • longitudinal monitoring of the development of Antifilarial antibodies and acquisition of wuchereria bancrofti in a highly endemic area of haiti
    PLOS Neglected Tropical Diseases, 2012
    Co-Authors: Katy L Hamlin, Mark L. Eberhard, Thomas B. Nutman, Jacquelin M. Roberts, Thomas G Streit, Joseph Kubofcik, Delynn M Moss, Jeffrey W Priest, Katherine Gass, Patrick J. Lammie
    Abstract:

    Antifilarial antibody testing has been established as a sensitive and specific method of diagnosing lymphatic filariasis. However, the development of serological responses to specific filarial antigens and their relationship to acquisition of infection is poorly understood. In order to evaluate whether the development of antigen specific Antifilarial antibodies precedes microfilaremia and antigenemia, we compared the antibody responses of serum samples collected between 1990 and 1999 from a cohort of 142 Haitian children followed longitudinally. Antigen status was determined using the Og4C3 ELISA and the presence of microfilaremia was detected using microscopy. Antibody responses to Wb123, a Wuchereria bancrofti L3 antigen, were measured using a Luciferase Immunoprecipitation System (LIPS) assay. Antibody responses to Bm14 and Bm33, Brugia malayi antigens and to a major surface protein (WSP) from Wolbachia were analyzed using a multiplex bead assay. Over follow-up, 80 (56%) of the children became antigen-positive and 30 (21%) developed microfilaremia. Detectable antibody responses to Bm14, Bm33, Wb123, and WSP developed in 95%, 100%, 92%, and 29% of children, respectively. With the exception of WSP, the development of antibody responses generally preceded detection of filarial antigen. Our results show that Antifilarial antibody responses can serve as an important epidemiological indicator in a sentinel population of young children and thus, may be valuable as tool for surveillance in the context of lymphatic filariasis elimination programs.

  • influence of infection with non filarial helminths on the specificity of serological assays for Antifilarial immunoglobulin g4
    Transactions of The Royal Society of Tropical Medicine and Hygiene, 2003
    Co-Authors: Andrew Muck, M L Pires, Patrick J. Lammie
    Abstract:

    Serological assays based on the detection of immunoglobulin (Ig) G4 antibodies to crude filarial extracts are widely used for epidemiological and diagnostic purposes. We tested 195 samples collected in 1998 from an area of Brazil where filariasis is not endemic and 13 (6.7%) had levels of Antifilarial IgG4 antibodies that were defined as positive. Both Strongyloides infection and the presence of Strongyloides antibody responses were associated with higher Antifilarial antibody responses. None of the specimens had a positive response to the Brugia malayi recombinant antigen (Bm14). These data suggest that serodiagnostic assays based on the use of crude filarial antigens should be interpreted with caution because of the potential for cross-reactivity with Strongyloides.

  • Reactivity to bacterial, fungal, and parasite antigens in patients with lymphedema and elephantiasis.
    The American Journal of Tropical Medicine and Hygiene, 2002
    Co-Authors: Jill B Baird, Jacquelin M. Roberts, Thomas G Streit, Jacky Louis Charles, David G. Addiss, Patrick J. Lammie
    Abstract:

    Both secondary infections and Antifilarial immunity are thought to play roles in the development and progression of lymphedema. To investigate this issue, immune responses to a panel of bacterial, fungal, and parasite antigens were examined for women with lymphedema and elephantiasis (n = 28) and for women with no clinical evidence of lymphatic dysfunction who were either microfilaremic (Mf+, n = 23) or microfilaria- and filarial antigen-negative (Ag-, n = 24). The prevalence and intensity of delayed-type hypersensitivity (DTH) responses was similar for most recall antigens; for individual antigens, lymphedema patients were significantly more likely to be reactive only to Proteus. Lymphedema patients with a history of three or more attacks of adenolymphangitis in the last 18 months showed increased DTH reactivity to Trichophyton. Proliferative responses to fungal and bacterial antigens were similar for all three groups; however, antigen-negative women, independent of disease status, mounted greater responses to filarial antigen. In contrast, lymphedema patients had higher levels of Antifilarial specific IgG1, IgG2, and IgG3 and higher IgG responses to streptolysin O than either Ag- or Mf+ women. In persons with lymphatic filariasis, immune reactivity is influenced by disease status as well as infection status.

  • longitudinal analysis of the development of filarial infection and Antifilarial immunity in a cohort of haitian children
    American Journal of Tropical Medicine and Hygiene, 1998
    Co-Authors: Patrick J. Lammie, Jacquelin M. Roberts, Merryl D Reiss, Kathleen A Dimock, Thomas G Streit, Mark L. Eberhard
    Abstract:

    Longitudinal studies are being conducted in Leogane, Haiti to investigate the relationship between acquisition of filarial infection and development of Antifilarial immunity as well as the impact of maternal infection on this relationship. Children (0-24 months of age) residing in Leogane were enrolled and were examined periodically to monitor parasitologic status and to collect serum for antigen and Antifilarial antibody determinations. To examine the development of filarial antigenemia and Antifilarial antibody responses in this cohort, serum samples were selected from a cross section of the population at two (n = 82) and four years of age (n = 76). Antigen prevalence increased from 6% among two-year-olds to more than 30% among four-year-olds, but in only one four-year-old child were microfilaria detected in a 20-microl smear. The proportion of antigen-positive children born to antigen-positive mothers was higher than the proportion of antigen-positive children born to antigen-negative mothers (9.8% versus 0% for two-year-olds; P = 0.15; and 39.6% versus 22.7% for four-year-olds; P = 0.18). Antifilarial IgG4 levels were significantly higher among antigen-positive children at both two and four years of age (P < 0.001). In analyses of paired samples, Antifilarial IgG4 responses increased significantly more among children who acquired infection by four years of age than among children who remained antigen negative, whereas Antifilarial IgG1 and IgG2 responses changed equally for antigen-positive and -negative children. Antifilarial antibody levels were not influenced by maternal infection status, but were significantly influenced by age, antigen status, and the neighborhood within the community. These results provide evidence that children acquire infection early in life and suggest that Antifilarial antibody responses may peak in early childhood.