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Gupta R.,Babu Banarasi Das National Institute of Technology and Management | Singh H.K.,Central Drug Research Institute CDRI | Singh H.K.,Azad Institute of Pharmacy and Research
Asian Pacific Journal of Tropical Disease

Objective: To ascertain the nootropic potential (memory enhancing effects) of the leaves of Alternanthera sessilis (Amaranthaceae) and Clerodendrum infortunatum (Verbenaceae) using rectangular maze and Y maze (interoceptive behavioral models). Methods: Methanolic extracts of leaves Alternanthera sessilis and Clerodendrum infortunatum dosed at 100 and 200 mg/kg each were administered to adult Swiss albino Wistar mice and the effect on acquisition, retention and retrieval of spatial recognition memory was determined. Bacopa monniera extract was used as the standard drug while Scopolamine hydrobromide served as the amnestic agent. Results: The higher doses of both the extracts exhibited a more promising nootropic potential. Maximal response was observed in the 200 mg/kg dose of Clerodendrum infortunatum methanolic extract, which closely approximated the results for the standard drug Brahmi. Both the higher doses elicited greater responses in both the models studied and were comparable to that achieved with the standard drug. Conclusions: The methanolic extracts of Clerodendrum infortunatum afforded greater memory enhancing effects in comparison to Alternanthera sessilis extract, the higher dose evoking pronounced alteration behavior and better learning assessments. © 2012 Asian Pacific Tropical Medicine Press. Source

Shameem M.,CSIR - Central Electrochemical Research Institute | Shameem M.,Central Drug Research Institute CDRI | Patel A.B.,CSIR - Central Electrochemical Research Institute

Background and Purpose: The effects of nicotine on cerebral metabolism and its influence on smoking behavior is poorly understood. An understanding of the chronic effects of nicotine on excitatory and inhibitory metabolic demand, and corresponding neurotransmission may provide clues for designing strategies for the optimal smoking cessation intervention. The objective of the current study was to investigate neuronal and astroglial metabolism in mice exposed to nicotine (0.5 and 2.0 mg/kg, sc) three times in a day for 4 weeks. Experimental Approach/Principal Findings: Metabolic measurements were carried out by co-infusing [U-13C6]glucose and [2-13C]acetate, and monitoring 13C labeling of amino acids in brain tissue extract using 1H-[13C] and 13C-[1H]-NMR spectroscopy. Concentration of 13C-labeled glutamate-C4 was increased significantly from glucose and acetate with chronic nicotine treatment indicating an increase in glucose oxidation by glutamatergic neurons in all brain regions and glutamate-glutamine neurotransmitter cycle in cortical and subcortical regions. However, chronic nicotine treatment led to increased labeling of GABA-C2 from glucose only in the cortical region. Further, increased labeling of glutamine-C4 from [2-13C]acetate is suggestive of increased astroglial activity in subcortical and cerebellum regions of brain with chronic nicotine treatment. Conclusions and Significance: Chronic nicotine exposure enhanced excitatory activity in the majority of brain regions while inhibitory and astroglial functions were enhanced only in selected brain regions. © 2012 Shameem, Patel. Source

Akhter F.,Integral University | Khan M.S.,Integral University | Singh S.,Central Drug Research Institute CDRI | Ahmad S.,Integral University

Advanced glycation end products (AGEs) are thought to contribute to the abnormal lipoprotein profiles and increased risk of cardiovascular disease in patients with diabetes and renal failure. D-ribose is one of the naturally occurring pentose monosaccharide present in all living cells and is a key component of numerous biomolecules involved in many important metabolic pathways. Formation of D-ribose derived glycated low density lipoprotein (LDL) has been previously demonstrated but no studies have been performed to assess the immune complex deposition in the kidney of rabbits immunized with glycated LDL. In this study, LDL was glycated with D-ribose, and it was further used as an immunogen for immunizing NZW female rabbits. The results showed that female rabbits immunized with D-ribose modified LDL induced antibodies as detected by direct binding and competitive ELISA. The modified LDL was found to be highly immunogenic eliciting high titer immunogen-specific antibodies, while the native forms were moderately immunogenic. The induced antibodies from modified LDL exhibited wide range of heterogeneity in recognizing various proteins and amino acids conformers. Furthermore, our histopathological results illustrated the deposits of immune complex in glomerular basement membrane in rabbits immunized with D-ribose-LDL. © 2014 Akhter et al. Source

Konwar R.,Central Drug Research Institute CDRI | Manchanda P.K.,Ohio State University | Chaudhary P.,Central Drug Research Institute CDRI | Lakshma Nayak V.,Central Drug Research Institute CDRI | And 2 more authors.
Asian Pacific Journal of Cancer Prevention

Glutathione S-transferases may be over expressed in benign prostate hyperplasia (BPH) but association of GST polymorphism with susceptibility to the disease is unclear. The objective of this study was to determine relationships between polymorphisms in the GSTM1, T1 and P1 genes with risk of symptomatic BPH and response to standard therapy. The study population comprised 160 symptomatic BPH patients with BPE (benign prostatic enlargement) and LUTS (lower urinary tract symptoms) and 200 age-matched controls. Patient inclusion criteria were: age >50 years; prostate size >30cm3; AUA (American Urological Association) score >7; and PVR volume ≤200 ml. Patients were treated with α-adrenergic blockers and 5α-reductase inhibitors for 6 months and subdivided based on significant improvement in parameters between pre and post combined therapy. The GSTT1 and GSTM1 variants genotyped with multiplex-PCR, whereas GSTP1 polymorphisms were determined with PCR-RFLP (polymerase chain reaction- restriction fragment length polymorphism). We observed a lack of any association with GSTT1 (p=0.45, OR=2.25, 95% CI=1.71-2.22) and GSTP1 (p=0.92 and 0.99) genes. There was a significant positive association with null alleles of the GSTM1 (p=0.000, OR=2.24, 95%CI =1.46-3.42) gene. Combined analysis of the three genotypes demonstrated further increase in the risk of symptomatic BPH (p=0.009, OR=8.31 95%CI=1.71-40.4). Polymorphisms of GST genes were not associated with rates for responders and non-responders. GSTM1 deletion is significantly associated with the increased risk of symptomatic BPH, but none of the GST polymorphisms appears associated with response to standard BPH therapy. Source

Manchanda P.K.,Ohio State University | Konwar R.,Central Drug Research Institute CDRI | Lakshma Nayak V.,Central Drug Research Institute CDRI | Singh V.,University of Lucknow | Bid H.K.,Central Drug Research Institute CDRI
Asian Pacific Journal of Cancer Prevention

Several genetic studies worldwide have recommended VDR as candidate gene for determining risk of benign prostate hyperplasia (BPH). We investigated the association between VDR gene polymorphisms and the risk of BPH in an Indian male population. Three polymorphic sites of VDR gene, viz., Fok-I, Taq-I and Bsm-I were genotyped in 160 BPH patients and 160 controls. Logistic regression models were used to determine the genetic effects using SPSS statistical software. A statistically significant association between VDR genotype (Taq-I and Bsm-I) and BPH (p=0.02 & 0.03) was obtained. In exploratory analyses, we also examined the association with responder and non-responder subgroups of patients for association of VDR (Taq-I) genotype with drug responsiveness. Our results established that Taq-I and Bsm-I genetic variants of VDR gene influence susceptibility BPH in Indian population. VDR genotypes specifically, Taq-I polymorphic variant is significantly associated with the improvement of BPH patients with standard drug therapy. Source

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