Central Drug Research Institute

About: Central Drug Research Institute is a facility organization based out in Lucknow, Uttar Pradesh, India. It is known for research contribution in the topics: Leishmania donovani & Brugia malayi. The organization has 4357 authors who have published 7257 publications receiving 143871 citations. The organization is also known as: Central Drug Research Institute, Lucknow & CDRI.

In vitro studies on the effect of certain natural products against hepatitis B virus.

Abstract: Picroliv (active principle from Picrorrhiza kurroa), its major components picroside I, catalpol, kutkoside I, kutkoside, andrographolide (active constituent of Andrographis paniculata), silymarin and Phyllanthus niruri extract were tested for the presence of anti hepatitis B virus surface antigen (anti HBs) like activity. HBsAg positive serum samples obtained from hepatitis B virus (HBV) associated acute and chronic liver diseases and healthy HBsAg carriers were used to evaluate the anti-HBs like activity of compounds/extract. The latter were mixed with serum samples and incubated at 37 degrees C overnight followed by HBsAg screening in the Elisa system. A promising anti-HBsAg like activity was noted in picroliv (and its major components) catalpol, P. niruri which differed from the classical viral neutralization. Picroliv also inhibited purified HBV antigens (HBsAg and HBsAg) prepared from healthy HBsAg carriers. The in vitro testing system appears to be a suitable model to identify an agent active against HBV, prior to undertaking detailed studies.

Immunization with the DNA-encoding N-terminal domain of proteophosphoglycan of Leishmania donovani generates Th1-type immunoprotective response against experimental visceral leishmaniasis.

Abstract: Leishmania produce several types of mucin-like glycoproteins called proteophosphoglycans (PPGs) which exist as secretory as well as surface-bound forms in both promastigotes and amastigotes. The structure and function of PPGs have been reported to be species and stage specific as in the case of Leishmania major and Leishmania mexicana; there has been no such information available for Leishmania donovani. We have recently demonstrated that PPG is differentially expressed in sodium stibogluconate-sensitive and -resistant clinical isolates of L. donovani. To further elucidate the structure and function of the ppg gene of L. donovani, a partial sequence of its N-terminal domain of 1.6 kb containing the majority of antigenic determinants, was successfully cloned and expressed in prokaryotic as well as mammalian cells. We further evaluated the DNA-encoding N-terminal domain of the ppg gene as a vaccine in golden hamsters (Mesocricetus auratus) against the L. donovani challenge. The prophylactic efficacy to the tune of ∼80% was observed in vaccinated hamsters and all of them could survive beyond 6 mo after challenge. The efficacy was supported by a surge in inducible NO synthase, IFN-γ, TNF-α, and IL-12 mRNA levels along with extreme down-regulation of TGF-β, IL-4, and IL-10. A rise in the level of Leishmania-specific IgG2 was also observed which was indicative of enhanced cellular immune response. The results suggest the N-terminal domain of L. donovani ppg as a potential DNA vaccine against visceral leishmaniasis.

Chitosan-Assisted Immunotherapy for Intervention of Experimental Leishmaniasis via Amphotericin B-Loaded Solid Lipid Nanoparticles

Abstract: Solid lipid nanoparticles (SLNs) have emerged as an excellent substitute over polymeric nanoparticles and, when incorporated with chitosan which activates the macrophage to impart an immune response, produce excellent results to fight against deleterious diseases like leishmaniasis where its parasite diminishes the immunity of the host to induce resistance. Based upon this hypothesis, chitosan-coated SLNs were developed and loaded with amphotericin B (AmB) for immunoadjuvant chemotherapy of Leishmania infection. Both uncoated and chitosan-coated AmB-loaded SLNs (AmB-SLNs) were fabricated using solvent emulsification and evaporation method. The various processes and formulation parameters involved in AmB-SLN preparation were optimized with respect to particle size and stability of the particles. In vitro hemolytic test credited the formulations to be safe when injected in the veins. The cellular uptake analysis demonstrated that the chitosan-coated AmB-SLN was more efficiently internalized into the J774A.1 cells. The in vitro antileishmanial activity revealed their high potency against Leishmania-infected cells in which chitosan-coated AmB-SLNs were distinguishedly efficacious over commercial formulations (AmBisome and Fungizone). An in vitro cytokine estimation study revealed that chitosan-coated AmB-SLNs activated the macrophages to impart a specific immune response through enhanced production of TNF-α and IL-12 with respect to normal control. Furthermore, cytotoxic studies in macrophages and acute toxicity studies in mice evidenced the better safety profile of developed formulation in comparison to marketed formulations. This study indicates that the AmB-SLNs are a safe and efficacious drug delivery system which promises strong competence in antileishmanial chemotherapy and immunotherapy.

Involvement of nitric oxide in neurodegeneration: a study on the experimental models of Parkinson's disease

Abstract: The present study was undertaken to explore involvement of nitric oxide (NO) in the experimental models of Parkinson's disease. Neurodegeneration was induced by unilateral injections of 6-hydroxydopamine (6-OHDA) or lipopolysaccharide (LPS) in the right striatum. Lesions were functionally evaluated by amphetamine-induced asymmetrical behaviour and by decrease in the tyrosine hydroxylase (TH) immunostaining. An induction in the expression of iNOS and augmentation in nitrite content was observed in both the models. The extent of increase in iNOS expression was, however, different but the elevation in the nitrite content was comparable in both the models. The increase in iNOS expression inversely correlated with the tyrosine hydroxylase (TH) immunolabeling. Animals pretreated with a NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), exhibited complete protection against amphetamine induced rotations in both the models. Thus, augmented NO availability subsequent to iNOS induction seems to play an important role in the initial phase of neurodegeneration.