PROTECTIVE ROLE OF BACOPA MONNIERI ON INDUCED PARKINSON'S DISEASE WITH PARTICULAR REFERENCE TO CATECHOLAMINE SYSTEM

Objective: Parkinson's disease (PD) is the second most neurodegenerative disorder. Bacopa monnieri (BM), an Indian herb extensively used in Ayurveda, used in treatments related to neurological complications was used now in our study. Methods: In the present experiment, rats were divided into four groups of six in each group: group 1 received saline water, group 2 received rotenone (RT) through i.p. for 60 days to induce PD, group 3 received for 20 days orally before induction of PD and group 4 received Levodopa (Reference drug; LD) orally. Results: The levels Dopamine (DA), Serotonin (5-HT), Epineprine (EP), Nor-epineprine (NEP) were decreased and Monoamine oxidase (MAO) activity was increased in different brain regions such as Cerebral cortex (CC), Cerebellum (CB), Mid brain (MB) and Pons medulla (PM) during induced PD compared with controls. These results were reversed after treatment with ethanolic extract of BM on par with reference drug (LD). Conclusion: Our results suggest the ability of BM extract to modulate catecholamine system in different brain regions of RT induced rodent model of PD and thus offers protection. When compared overall the BM is better than the LD drug. The BM may provide a platform for future drug discoveries and novel treatment strategies in PD and can act as antiparkinsonian agent

HOMOLOGY MODELING AND DEVELOPMENT OF DIHYDRODIPICONILATE REDUCTASE INHIBITORS OF KLEBSIELLA PNEUMONIA: A COMPUTATIONAL APPROACH

Objective: In order to development of novel, potent and selective inhibitors of Dihydropiconilate reductase (KpDHDPR) of multidrug resistant Klebsiella pneumonia. Methods: Protein sequence of KpDHDPR was retrieved from the UNIPROT and the primary and secondary structure was analyzed using Prot Param, SOPMA, GOR4 and Chou and Fasman. Afterword's, 3D structure of KpDHDPR was built by using MODELLEER9.14. The Molecular dynamics simulation was carried out using NAMD2.9 with CHARMM27 force field for 10 picoseconds and production run with for 400 picoseconds time period covered with water box. Molecular docking and virtual screening was carried out using Auto Dock Vina4.0 with PyRx interface. Bond angles, bond lengths, bond distances and binding interactions were analyzed using PyMol. Toxicity assessment and Lipinski rule of five of ligand were assessed using MOLINSPIRATION and OSIRIS Server. Results: 3D structure of KpDHDPR was resolved on the basis of EcDHDPR that revealed N-terminal nucleotide domain and C-terminal substrate binding domain which are connected by a short hinge region. Nucleotide binding domain is formed with seven α-helices and the Substrate binding domain is composed with three α-helices and Rossman fold is observed with four α-helices and seven β-strands. Molecular docking analysis revealed that NADPH has exhibited more binding affinity to KpDHDPR than NADH. As results of virtual screening and docking, six compounds viz. ZINC04280533, ZINC04280532, ZINC04280468, ZINC33378709, ZINC05280538 and ZINC25694354 were identified. Bioavailability of these inhibitors are comply with the Lipinski rule of five, good pharmacokinetic and drug likeness properties. Conclusion: In conclusion, in silico studies revealed that these lead scaffolds could helpful in the development of KpDHDP R inhibitors. Hence, these drug candidates might be promoted as promising antibacterial agents for the treatment of drug resistant gram negative bacterial infections

Isolation and characterization of a novel lepidopteran-selective toxin from the venom of South Indian red scorpion, Mesobuthus tamulus

BACKGROUND: Scorpion venom contains insect and mammal selective toxins. We investigated the venom of the South Indian red scorpion, Mesobuthus tamulus for the purpose of identifying potent insecticidal peptide toxins. RESULTS: A lepidopteran-selective toxin (Buthus tamulus insect toxin; ButaIT) has been isolated from this venom. The primary structure analysis reveals that it is a single polypeptide composed of 37 amino acids cross-linked by four disulfide bridges with high sequence homology to other short toxins such as Peptide I, neurotoxin P2, Lqh-8/6, chlorotoxin, insectotoxin I5A, insect toxin 15 and insectotoxin I1. Three dimensional modeling using Swiss automated protein modeling server reveals that this toxin contains a short α-helix and three antiparallel β-strands, similar to other short scorpion toxins. This toxin is selectively active on Heliothis virescens causing flaccid paralysis but was non-toxic to blowfly larvae and mice. CONCLUSION: This is the first report of a Heliothine selective peptide toxin. Identification of diverse insect selective toxins offer advantages in employing these peptides selectively for pest control

Carbamates of sulfathiazole and methyl tryptophanate: Synthesis, antimicrobial activity and docking studies against DNA gyrase A

1384-1397It is well demonstrated that bacteria have become resistant to common medications recently and it is considered to be one of the major threats to human health. The research on innovative antimicrobial agents explores a vast and interesting subject area. Therefore, a series of new carbamate derivatives of sulfathiazole 6a-e, a common oral antimicrobial drug and methyl tryptophanate 8a-e, N-methyl α-amino acid ester containing indole moiety have been synthesized. Structures of the title products have been elucidated by spectral analyses like IR, NMR (1H and 13C), mass and elemental composition. The compounds have been evaluated for their in vitro antimicrobial activity including minimum inhibitory concentrations (MICs). Whereas, three carbamate derivatives of sulfathiazole 6a, 6b and 6e and one derivative of methyl tryptophanate 8a show promising antibacterial activity in the range of MIC 2.88-8.14 µg/mL and it is a comparable activity of streptomycin (MIC = 3.14-7.43 µg/mL). Most of the compounds provide potent activity against E. coli which is equivalent to streptomycin (MIC = 3.14 µg/mL). The title compounds have been docked into the active site of E. coli DNA gyrase A enzyme to ensure the binding mode and the results demonstrate that a few compounds show better binding energies with enzyme than that of standard, streptomycin and associated with antibacterial activity

ZnBr2-SiO2 catalyzed green synthesis of tetrazoles: Molecular docking and antioxidant activity studies

A series of 5-substituted and 1,5-disubstituted tetrazoles were synthesized in high yields from various biologically active substituted nitriles with sodium azide under heterogeneous catalysed (ZnBr2-SiO2) [2+3] cycloaddition conditions. This reaction gave an excellent yield in the presence of catalytic amount of 0.2 g of ZnBr2-SiO2, glycerol solvent system under microwave irradiation conditions. All the prepared compounds were characterized by elemental analysis 1H NMR, 13C NMR, FT-IR, and mass spectral data. The newly synthesized compounds were investigated for their respective molecular target using molecular docking studies. The results reveal that compounds 5a, 5c, 5e and 3e have conferred with multi target property. The compounds 5a, 5c and 5e have shown the highest binding affinities of -10.1, -9.7 and -10.6 with reverse transcriptase, -8.5, -8.2 and -8.9 with Aurora B, respectively. The compounds 5a, 5e and 3e have shown -8.9, -8.5 and 8.4 with Aromatase, respectively. In addition, the antioxidant activity data reveals that all the compounds showed good antioxidant activity, particularly the compounds 3d, 5d, and 5e exhibited promising radical scavenging activity

Evaluation of Microbial Enzymes in Normal and Abnormal Cervicovaginal Fluids of Cervical Dysplasia: A Case Control Study

The aim of the present study was to evaluate the role of microbial enzymes in normal and abnormal cervicovaginal fluids of cervical dysplasia. The cervicovaginal infections were evaluated through the estimation of microbial enzymes in patients with and without abnormal cervical cytology like bacterial and fungal infections. The patients were categorized based on infection caused by organism and stages of dysplasia. The pH, Whiff test, and Pap smear tests were conducted for normal and abnormal cervical swabs based on standard protocols. Microbial enzymes include mucinase, sialidases, and proteases of the cervical swabs and are estimated according to standard methods. The results of abnormal cervical cytological smears showed increased pH and the presence of amines with different levels of Pap smear test. Increased levels of microbial enzymes were observed in patients with abnormal cytology than normal cytology. Three microbial enzymes mucinase, sialidase, and protease were significantly (P<0.01) more elevated in patients with bacterial infections (8.97±0.64, 10.39±0.28, 8.12±0.64) than without dysplasia (2.02±0.8, 1.98±0.3, 1.96±0.8). The results reinforce that the microbial infection seems to be more prone to cervical dysplasia and may act as risk-factor for the development of cervical cancer along with HPV infection

EVALUATION OF ROTENONE INDUCED PARKINSON&apos;S DISEASE ON GLUTAMATE METABOLISM AND PROTECTIVE STRATEGIES OF BACOPA MONNIERI

ABSTRACT: Bacopa monnieri (BM; Family: Scrophulariaceae), also referred as Brahmi has been used for centuries in Ayurvedic system of medicine as a brain tonic, memory enhancer, revitaliser of sensory organs, antianxiety, cardio-tonic, diuretic, antidepressant and anticonvulsant agent, and the pharmacological actions are mainly attributed to the saponin compounds present in the alcoholic extract of the plant. The present study was carried out with a specific aim to examine the neuroprotective effect of Rotenone (RT) induced Parkinson&apos;s disease (PD) with particular reference to glutamate metabolism in different regions of rat brain. The rats were divided into four groups of six in each, group 1 received Saline water, group 2 received RT through i.p. route for 60 days to induce PD. The BM extract was given orally 20 days before induction of the PD to group 3 and group 4 received Levodopa (LD) orally, referred as drug control. The levels of Glutamine content, Glutamate dehydrogenase (GDH), Glutamine synthetase (GS) and Glutaminase were measured. Glutamine content and activity levels of GDH, GS were significantly depleted and elevated Glutaminase activity was found in different brain regions of rat during RT induced PD when compared to control rats. Treatment with BM and LD caused significant elevation in Glutamine content and the activity levels of GDH, GS and depletion in glutaminase activity in different brain regions of rats when compared to induced PD rats. Our results suggest the ability of BM extract to modulate glutamate metabolism in different brain regions of induced rodent model of PD

Protective role of Bacopa monnieri against Rotenone- induced Parkinson’s disease in PC 12 cell lines

 Parkinson disease (PD) is a chronic neurodegenerative disorder characterized by the loss of dopaminergic (DA) neurons in the substantia nigra, decreased striatal dopamine (DA) levels, and consequent extrapyramidal motor dysfunction. PC 12 cells originate from pheochromocytoma cells of rat adrenal medulla and share many common characteristics with substantia nigra cells. They produce DA, several growth factors, such as nerve growth factor, fibroblast growth factor and transforming growth factor, and express DA receptors. Hence, these cells are being used to study the alterations in dopaminergic neurons, in vitro, that occur during Parkinson’s disease. Since long term usage of antiparkinsonian drugs cause high incidence of pharmacoresistence and untoward side effects, attention has been paid in recent years to screen bioactive compounds from natural medicinal plants for treatment of several neurological disorders including Parkinson’s disease. Keeping in view of relative importance of natural medicinal plants, the present study is mainly focused to characterize the anti-parkinsonian effect of Bacopa monnieri (BM), an Indian herb which is being extensively used in Ayurveda treatments related to neurological complications. The present study was designed to assess the neurotoxicity of rotenone on DA-producing PC12 cells and explore the possible antiparkinsonian effect of BM in comparing with Levodopa (LD) (Reference control). The survivability studies of PC 12 cell-lines were analysed using MTT assay. Pre-treatment with BM extract significantly ameliorated morphological damage, cell viability, and apoptosis of PC12 cells exposed to RT. Hence BM extract can be effectively used in the treatment of PD and other related neurological disorders

Antiviral activity and Antioxidant role of phenolics from Sophora interrupta Bedd in NDV induced oxidative stress in chickens

The present investigation is taken up to evaluate the antiviral efficacy of phenolics isolated from Sophora interrupta Bedd and their antioxidant role in the brain and lungs of chicken during Newcastle disease virus (NDV) induced oxidative stress. The activity levels of selected antioxidant enzymes such as superoxide dismutase (SOD), catalyse (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) levels were significantly decreased in brain and lung tissues of  NDV infected animals over controls causing oxidative stress. In addition, histopathological alterations disclosed that lungs of NDV infected chicken were affected severely as evidenced by the alterations in alveolar cell morphology, congestion, necrotic and degenerative changes whereas degeneration of Purkinje cells, neuronal necrosis, degeneration in myelin sheath and compression of cells were observed in the brain of NDV infected chickens. These reduced antioxidant defence mechanisms and histopathological abnormalities were restored to normal when chicken were pre-treated with the phenolics isolated from Sophora interrupta Bedd at the dose of 300 mg/Kg Bw/day for one week. Pre-treatment with the phenolics isolated from the above medicinal plant also caused significant reduction in the titre levels of NDV. These results suggest that pre-treatment with the phenolics isolated from Sophora interrupta Bedd exhibited significant antiviral activity and thus the plant extract may be used as a prophylactic treatment for the prevention of NDV infection in chicken