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Dietary compounds play an important role in the prevention and treatment of many cancers, although their specific molecular mechanism is not yet known. In the present study, thirty dietary agents were analyzed on nine drug targets through in silico studies. However, nine dietary scaffolds, such as silibinin, flavopiridol, oleandrin, ursolic acid, α-boswellic acid, β-boswellic acid, triterpenoid, guggulsterone, and oleanolic acid potentially bound to the cavity of PI3K-α, PKC-η, H-Ras, and Ras with the highest binding energy. Particularly, the compounds silibinin and flavopiridol have been shown to have broad spectrum anticancer activity. Interestingly, flavopiridol was embedded in the pockets of PI3K-α and PKC-η as bound crystal inhibitors in two different conformations and showed significant interactions with ATP binding pocket residues. However, complex-based pharmacophore modeling achieved two vital pharmacophoric features namely, two H-bond acceptors for PI3K-α, while three are hydrophobic, one cat-donor and one H-bond donor and acceptor for PKC-η, respectively. The database screening with the ChemBridge core library explored potential hits on a valid pharmacophore query. Therefore, to optimize perspective lead compounds from the hits, which were subjected to various constraints such as docking, MM/GBVI, Lipinski rule of five, ADMET and toxicity properties. Henceforth, the top ligands were sorted out and examined for vital interactions with key residues, arguably the top three promising lead compounds for PI3K-α, while seven for PKC-η, exhibiting binding energy from − 11.5 to − 8.5 kcal mol−1. Therefore, these scaffolds could be helpful in the development of novel class of effective anticancer agents. © 2021, The Author(s). We are grateful to the National Natural Science Foundation of China (grant numbers: 31071152 and 31171209) for providing research fund to WG.

Epilepsy is a chronic central nervous system disorder that occurs not only with the imbalance of glutamatergic neurons and inhibitory gamma-aminobutyric acid (γ-GABA) neurons, but also with abnormal Central cholinergic neuronal regulation. Since long term usage of antiepileptic drugs cause high incidence of pharmacoresistance and untoward side effects, attention has been paid in recent years to screen bioactive compounds from natural medicinal plants for the treatment of several neurological disorders including Epilepsy. Keeping in view of relative importance of natural medicinal plants, the present study is mainly focused to characterize the anti-convulsant effect of Bacopa monnieri (BM), an Indian herb which is being extensively used in Ayurvedic treatments related to neurological complications. The present study is designed to assess the neurotoxicity of Pentylene tetrazole (PTZ), an epileptic compound with particular reference to Cholinergic system and ATPases in different brain regions of rat to explore the possible antiepileptic effect of different extracts of BM in comparison with Diazepam (DZ) (Reference control). The activity levels of Acetyl cholinesterase (AChE) and ATPases were decreased in different regions of brain during PTZ induced epilepsy which were increased in epileptic rats pretreated with different extracts of Bacopa monnieri except EAE and AE. In addition Acetylcholine (ACh), levels were increased during PTZ induced epilepsy when compared with normal control and levels were reversed on pretreatment with different extracts of BM. Recoveries of these parameters suggest that the bioactive factors present in the extracts offer neuroprotection by interrupting the pathological cascade that occurs during epileptogenesis.

Different kinds of secondary metabolites present in the medicinal plants play an important role to alleviate different human ailments including neurodegenerative disorders such as Parkinson's, Alzheimer's, epilepsy and schizophrenia etc. Recently we have isolated and characterized a novel bioactive compound viz. 3-(3,4-dimethoxy phenyl)-1-4(methoxy phenyl)prop-2-en-1-one from the methanolic extract of Celastrus paniculatus (CP) which has been widely used for the treatment of neurodegenerative diseases. The present investigation is mainly aimed to evaluate the neuroprotective potential of the above bioactive compound against ketamine-induced schizophrenia with particular reference to catecholaminergic metabolism using in vivo and in silico methods. Ketamine-induced schizophrenia caused significant elevation in biogenic amines (epinephrine, nor epinephrine, dopamine and 5-HT) and monoamine oxidase activity levels which were restored to normal during the treatment with the bioactive compound akin to the reference compound, clozapine. In addition, the compound has shown highest binding score against all the biogenic amine receptors viz. D1, D2, D3, D4 and serotonin receptor, 5-HT2A with lowest inhibition constant values than the reference compound, clozapine. The present findings suggest that modulation of CNS monoamine neurotransmitter system might partly contribute to the impairments associated with schizophrenia and the plant compound alleviates the monoaminergic abnormalities associated with the neurological dysfunction.Communicated by Ramaswamy H. Sarma.

Synthesis of a series of new urea and thiourea compounds have been accomplished by the reaction of 2,3-dihydro-1H-inden-1-amine with various phenyl isocyanates and isothiocyanates. These compounds were evaluated for their antioxidant activity by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and nitric oxide (NO) radical scavenging assay methods including IC50 values. Some of the compounds exhibited potential activity in the two tested methods. Among the series of compounds, urea derivative linked with 4-bromo phenyl ring (4b), and thiourea derivatives bonded with phenyl ring (4e), 4-fluoro phenyl ring (4f) and 4-nitro pheyl ring (4h) were found to exhibit promising anti oxidant activity with low IC50 values. Where four of the title comounds exhibited higher bindig energies than the reference compound (Imatinib) in in silico molecular docking studies with Aromatase. All the synthesized compounds were characterized by IR, 1H, 13C NMR and mass spectral data.

A simple method was employed for the synthesis of dihydropyrano[3, 2-b]chromenedione derivatives (4a-o) in high yields by condensation of 5, 5-dimethylcyclohexane-1, 3-dione(1), different aromatic aldehydes (2a-o), and 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one(3), using meglumine as a stable and reusable catalyst. Meglumine, an amino sugar, was employed as an environmentally benign catalyst, due to its splendid properties such as being inexpensive, recyclable, and biodegradable. The accomplished protocol employs low catalyst loading and easy work-up for the synthesis of 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one derivatives. A great asset is that without any significant loss, the catalyst could be recovered and reused for extended synthetic steps. This offer huge advantage to overcome recyclability issues. Our synthesized compounds were analyzed by IR, 1H, 13C NMR, mass spectra and evaluated for their antioxidant properties by 1, 1-diphenyl-2-picryl hydrazyl radical (DPPH), hydrogen peroxide(H2O2), and nitric oxide (NO) scavenging methods. The correlation in exhibition of antioxidant activity was effective at all doses. The binding interactions and molecular docking studies for entitled compounds were studied against 3MNG protein; 4k exhibited marked binding affinity with excellent docking score of −7.6 Kcal/mol and emerged as a lead compound. © 2019 Wiley Periodicals, Inc. Ural Federal University, UrFU The authors G. Sravya and N. Bakthavatchala Reddy are thankful to Ural Federal University, Yekaterinburg, Russia, for postdoctoral fellowship.

Different kinds of secondary metabolites present in the medicinal plants play an important role to alleviate different human ailments including neurodegenerative disorders such as Parkinson's, Alzheimer's, epilepsy and schizophrenia etc. Recently we have isolated and characterized a novel bioactive compound viz. 3-(3,4-dimethoxy phenyl)-1-4(methoxy phenyl)prop-2-en-1-one from the methanolic extract of

Epilepsy, a common chronic neurological disorder characterized by repeated, spontaneous seizures, also known as seizure disorder. Seizure related neuronal injury has been assumed to be mediated by glutamate, the excitatory amino acid, in the central nervous system that causes a sudden imbalance between the inhibitory and excitatory signals in the brain with glutamate, γ-aminobutyric acid (GABA), noradrenaline, serotonin, and dopamine. Since long term usage of antiepileptic 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 Epilepsy. Keeping in view of relative importance of natural medicinal plants, the present study is mainly focused to characterize the anti-convulsant effect of Bacopa monnieri (BM), an Indian herb which is being extensively used in Ayurvedic treatments related to neurological complications. The present study is designed to assess the neurotoxicity of Pentylene tetrazole (PTZ), an epileptic compounds, on the Glutamate metabolism and Amino transferases in different brain regions (Cerebral cortex, Cerebellum, Pons medulla and Hippocampus) of rat and to explore the possible antiepileptic effect of different extracts (Ethanol, n-Hexane, Chloroform, Ethyl acetate, n-Butanol and Aqueous extracts) of BM in comparison with Diazepam (DZ) (Reference control). The activities of glutamate dehydrogenase (GDH), glutamine synthetase (GS) and glutamine content were decreased in different regions of brain during PTZ induced epilepsy which were increased in epileptic rats pretreated with different extracts of Bacopa monnieri except EAE and AE. Glutaminase activity was increased in PTZ induced epilepsy and decreased on pretreatment with all the extracts of BM except AE. In addition aspartate (AAT) and alanine aminotransferase (ALAT) activity levels were increased during PTZ induced epilepsy when compared with normal control and levels were reversed on pretreatment with different extracts of BM. Recoveries of these parameters during antiepileptic treatment suggest that the bioactive factors present in the extracts offer neuroprotection by interrupting the pathological cascade of glutamatergic hyperexcitation that occurs during epileptogenesis.

In an attempt to find potential neuroprotective agents, a series of novel 3-(1-((1-(substituted phenyl)-1H-1,2,3-triazol-4-yl) methoxyimino) ethyl)-2H-chromen-2-one derivatives 6a–j were synthesized by using “click reaction” and evaluated for their in vitro neuroprotectivity and toxicity against H2O2-induced PC12 cell lines by using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) reduction assay. Most of them exhibited moderate to good activity in which compound 6e was found to have significant protectivity with cell viability of 94.51 ± 0.68% at 50 µg/ml concentration and half-maximal effective concentration (EC50) value of 14.04 µg/ml against injured PC12 cell lines and low toxicity with half-maximal cytotoxic concentration (CC50) value of 544.88 µg/ml. Furthermore, molecular docking was carried out in order to understand plausible binding modes of novel derivatives with the active site of glycogen synthase kinase-3β enzyme, and the results were well complemented by the in vitro neuroprotective results against H2O2-induced PC12 cell lines. Additionally, in silico ADME properties showed drug likeness with good oral absorption and moderate blood–brain barrier permeability. The structures of all the synthesized compounds were confirmed by 1H NMR, 13C NMR, IR and LC–MS analyses.

The discovery and development of novel antiviral drugs from natural sources is continuously increasing due to limitations of currently available drugs such as toxic side effects, drug residue risk factors, high costs, and poor therapeutic strategies. Also, there are very few known antiviral drugs that are effective against only specific viruses. Hence, the present study is intended to isolate and characterize potent antiviral compounds from the methanolic root extract ofSophora interruptaBedd. against avian paramyxovirus, Newcastle disease virus (NDV) and to distinguish the molecular basis of antiviral compounds. The two isolated flavonoids, maackiain (SR-1) and echinoisoflavanone (SR-2) exhibited the best antiviral activities against NDV infection in chicken embryo fibroblast cell lines compared to the standard antiviral drug, Ribavirin. Further, thein vitrostudies and quantitative PCR analysis suggests that these flavonoids inhibit the viral entry, replication, and transcription, which may be beneficial as a promising strategy for the treatment of viral infections. Besides, the molecular docking studies ofSR-1andSR-2exhibited high binding affinities of −7.6 and −8.0 kcal mol−1, respectively, and marked interactions with the NDV surface glycoprotein, hemagglutinin neuraminidase (HN). Also, thein silicotoxicity properties as well pharmacokinetic studies of isolates revealed them as pharmacologically potent antiviral compounds. © The Royal Society of Chemistry 2020. Council of Scientific and Industrial Research, India, CSIR The author WR thanks the Council of Scientic and Industrial Research (CSIR), New Delhi and the authors CB, AR, and PR are grateful to UGC-BSR, New Delhi for nancial assistance under CSIR-MRP and UGC-RFSMS (BSR) programs. Furthermore, all the authors are thankful to National Institute of Animal Biotechnology (NIAB), Hyderabad for providing laboratory facilities to carry out the viral studies.

The present study was carried out with the specific aim to evaluate anti-Helicobacter pylori (Hp) and urease inhibitory activities of three flavonoids, namely 5-hydroxy-7,4′-dimethoxy-6,8-di-C-methylflavone (1), kaempferol-3-O-β-D-glucopyranoside (2) and kaempferol-3-O-α-L-rhamnopyranoside (3), of Syzygium alternifolium fruits. These flavonoids were examined for anti-H. pylori activity against two Hp strains, Hp 26695 and Hp P12, through a microbroth dilution assay with a time kill kinetics study and also the evaluation of their ability to lower H. pylori colonization with AGS (gastric epidermal cells). In addition, a urease inhibition assay was performed with these compounds, followed by 2D QSAR, molecular docking and molecular dynamics simulations on these compounds with target proteins, urease and cytotoxin associated gene (Cag A). The in vitro studies showed that compounds 2 and 3 show significant anti-H. pylori activity whereas compound 1 exhibits moderate activity when compared to amoxicillin and that these compounds also show strong bactericidal kinetics in a time dependent manner. These compounds potentially reduce the H. pylori colonization with a significant loss of its adhesion with AGS cells and inhibit the Hp urease activity. 2D QSAR analysis reveals that these compounds exhibit an acceptable correlation of RMSE = 0.905 and R2 = 0.820 with the biological assays. The compounds show strong inhibitions by forming H-bonding interactions with the active pocket residues of the target proteins as evidenced by 10 ns molecular dynamics simulations. Hence, the current investigation will provide a new vision for the discovery of potent antimicrobial agents from natural sources against H. pylori infections.

Multidrug resistant (MDR) gram negative bacterial infections are most prevalent in the hospitals which are truly untreatable and remedial verdict are very deprived. In the current investigation, two compounds (Quercetin and Pinitol) and fractions have been isolated and characterized from Indigofera barberi using chromatographic and NMR studies. Antimicrobial assays reveal IB-Me, IB-D and IB-E fractions and quercetin have shown eloquent antimicrobial activity on clinically isolated bacteria such as Pseudomonas aeruginosa, E. coli, Klebsiella pneumonia and Citrobacter sp. Molecular docking studies demonstrated quercetin has exhibited highest binding affinity with DNA gyrase B and subsequently eleven pharmacophore features viz . five HBD/HBA, two hydrophobic, one HBA and three aromatic (Pi) rings were identified using MOE. Pharmacophore based virtual screening, docking, binding energies and binding affinity with Born-volume (GB/VI) studies demonstrated thirteen lead molecules which were specifically interacted with Asn46, Asp73, Arg76, Thr163, Lys103, Arg136 residues and conserved water molecules within ATP pocket of DNA gyrase B. These scaffolds comply with Lipinski rule of five, toxicity and drug likeness properties deliberated as drug compounds. Hence, these compounds could be endorsed as persuasive DNA gyrase B inhibitors which can be considered as novel compounds in the clinical management of MDR Gram negative bacterial infections.

The female genital tract is a complex of microbial colonization, which shows a prominent role in the development of either a healthy or diseased condition. The aim of the present review is to describe the diverse components of both the protective and defective mechanisms induced by microbial species present in the female genital tract. The protective mechanism was induced by indigenous microbial flora colonized in the female genital tract, which includes innate immunity, secretions containing cytokines, antimicrobial peptides and inhibitory substances like organic acids, H2O2, bacteriosin and toll-like receptors. On the other hand, abnormal microorganisms produce virulence factors and enzymes, which cause life-threatening infectious diseases including cancer. The review summarizes that depending upon the presence and/or absence of normal and abnormal microorganisms, the female genital tract shows either a healthy and/or infectious condition.

Emerging drug resistance in clinical isolates of Staphylococcus aureus might be implicated to the overexpression of NorA efflux pump which is capable of extruding numerous structurally diverse compounds. However, NorA efflux pump is considered as a potential drug target for the development of efflux pump inhibitors. In the present study, NorA model was constructed based on the crystal structure of glycerol-3-phosphate transporter (PDBID: 1PW4). Molecular dynamics (MD) simulation was performed using NAMD2.7 for NorA which is embedded in the hydrated lipid bilayer. Structural design of NorA unveils amino (N)- and carboxyl (C)-terminal domains which are connected by long cytoplasmic loop. N and C domains are composed of six transmembrane α-helices (TM) which exhibits pseudo-twofold symmetry and possess voluminous substrate binding cavity between TM helices. Molecular docking of reserpine, totarol, ferruginol, salvin, thioxanthene, phenothiazine, omeprazole, verapamil, nalidixic acid, ciprofloxacin, levofloxacin, and acridine to NorA found that all the molecules were bound at the large hydrophobic cleft and indicated significant interactions with the key residues. In addition, structure-based virtual screening was employed which indicates that 14 potent novel lead molecules such as CID58685302, CID58685367, CID5799283, CID5578487, CID60028372, ZINC12196383, ZINC72140751, ZINC72137843, ZINC39227983, ZINC43742707, ZINC12196375, ZINC66166948, ZINC39228014, and ZINC14616160 have highest binding affinity for NorA. These lead molecules displayed considerable pharmacological properties as evidenced by Lipinski rule of five and prophecy of toxicity risk assessment. Thus, the present study will be helpful in designing and synthesis of a novel class of NorA efflux pump inhibitors that restore the susceptibilities of drug compounds.

A series of new urea and thiourea derivatives of 5-hydroxy tryptophan 3a-l was designed and synthesized from 5-hydroxy tryptophan (1) by treating various isocyanates 2a-g and isothiocyanates 2h-l in the presence of triethylamine (TEA) as a base. The antioxidant activities of the newly synthesized compounds were evaluated by using different in vitro assays such as 1, 1-diphenyl-2-picrylhydrazyl (DPPH), hydrogen peroxide (H2O2) and superoxide. The results obtained from the in vitro studies revealed that the compounds 3a, 3g, 3h, and 3l exhibited the significant high content of antioxidant activity. Besides, molecular docking studies indicated that, all the compounds 3a-l have formed higher binding energies with 3MNG protein than the reference compound 1. Among all the synthesized compounds, 3a, 3l, 3g, 3b, 3c and 3h have exhibited the highest dock scores than the rest of the compounds including the reference compound. Hence, it is concluded that the title compounds will open new vistas for the discovery of strong antioxidants and will stand as remarkable antioxidant moieties in future.

An efficient and convenient Meglumine catalyzed procedure for the synthesis of bis(indolyl) methanes at ambient temperature under aqueous conditions in high yields. The catalytic reaction proceeds very smoothly. Clean reaction, ease of product isolation/purification, easily available reactants, metal free and environmentally friendly reaction conditions are the notable advantages of the present methodology. All the entitled compounds were characterized by IR, 1H, 13C NMR, mass spectra and evaluated for their antioxidant (DPPH, H2O2 and NO scavenging methods). They exhibited potent in vitro antioxidant activity dose-dependently. The binding interactions and molecular docking studies for entitled compounds were studied against 3MNG protein. 4d exhibited marked binding affinity with excellent docking score of −7.6 K.cal/mol and emerged as a lead compound.

A green synthesis of amino acid-substituted methylene bisphosphonates (4a-j) is achieved via a one-pot, three-component reaction of dialkylphosphite, triethyl orthoformate, and various amino acids ...

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.

In order to increase the binding energy with haemaglutinin–neuraminidase (HN) protein of Newcastle disease virus (NDV), to improve the membrane permeability and to increase antiviral activity, modified structures of didanosine (ddI) were designed by phosphorylation and substitution with various bio-active amines. The designed derivatives revealed better binding energy values (in between −7.9 and −10.6 kcal/mol) than ddI (−7.3 kcal/mol) with HN of NDV. The docking simulations were encouraged for synthesis and screening of their antiviral activity against NDV in the chicken embryonated eggs. In vitro antibacterial activity is also evaluated for the title compounds. The title compounds exhibited three times of improved antiviral activity than that of the parent compound (ddI). In addition to this the title compounds were performed as good antibacterial agents.

Objectives To evaluate the effectiveness of radiochemotherapy and chemotherapy on human papilloma virus induced cervical cancer patients by the estimation of serum proteins and magnetic resonance imaging. Methods HPV 16/18 viral DNA was detected in the plasma of cervical cancer patients ( n = 50) by PCR using HPV consensus primers. Of the 50 cervical cancer patients, 25 cases undergoing radiation with chemotherapy and another 25 cases undergoing chemotherapy. Levels of pre- and post-treated serum squamous cell carcinoma antigen, soluble CD44, cancer antigen-125 were measured and evaluated the tumour size at pre- and post-radiation based on magnetic resonance images. The effectiveness of treatment was evaluated in terms of protein levels and represented as whisker line graphs. Results Of the amplified 50 samples, HPV 16 and 18 strains were identified as 48 and 44%, respectively. Serum protein levels were significantly increased in both pre-treated groups when compared to healthy group. Post-treated (radiotherapy) cervical cancer patients’ shows decreased tumour size when compared to pre-treated groups. Taking consideration of proteins, squamous cell carcinoma antigen, soluble CD44, cancer antigen-125 levels are more decreased in patients treated with radiochemotherapy than chemotherapy alone. The decreased levels of proteins were significantly higher in early stage of the cervical cancer than the advanced stage of cancer patients. Conclusion Serum levels of protein markers are more improved in patients treated with radiochemotherapy than chemotherapy hence, radiochemotherapy may be the best choice of treatment with reference to proteins at early stage of cervical cancer when compared to chemotherapy alone.

Continuous usage of synthetic chemotherapeutic drugs causes adverse effects, which prompted for the development of alternative therapeutics for gastric cancer from natural source. This study was carried out with a specific aim to screen gastroprotective compounds from the fruits of Syzygium alternifolium (Myrtaceae). Three flavonoids, namely, 1) 5-hydroxy-7,4′-dimethoxy-6,8-di-C-methylflavone, 2) kaempferol-3-O-β-d-glucopyranoside, and 3) kaempferol-3-O-α-l-rhamnopyranoside were isolated from the above medicinal plant by employing silica gel column chromatography and are characterized by NMR techniques. Antigastric cancer activity of these flavonoids was examined on AGS cell lines followed by cell cycle progression assay. In addition, pharmacophore-based screening and molecular dynamics of protein–ligand complex were carried out to identify potent scaffolds. The results showed that compounds 2 and 3 exhibited significant cytotoxic effect, whereas compound 1 showed moderate effect on AGS cells by inhibiting G2/M phase of cell cycle. Molecular docking analysis revealed that compound 2 has higher binding energies on human growth factor receptor-2 (HER2). The constructed pharmacophore models reveal that the compounds have more number of H-bond Acc/Don features which contribute to the inhibition of HER2 activity. By selecting these features, 34 hits were retrieved using the query compound 2. Molecular dynamic simulations (MDS) of protein–ligand complexes demonstrated conspicuous inhibition of HER2 as evidenced by dynamic trajectory analysis. Based on these results, the compound ZINC67903192 was identified as promising HER2 inhibitor against gastric cancer. The present work provides a basis for the discovery a new class of scaffolds from natural products for gastric carcinoma.

Ricinus communis (RC) is a traditional medicinal plant which has been used by Chenchu and Yerukula tribes for treating their liver ailments. The present work is aimed to explore the hepatoprotective efficacy of Ricinus communis against d -galactosamine (D-GalN) induced hepatitis rat model and its therapeutic potential compared with standard drug, silymarin (100 mg/kg.bw). In vitro antioxidant activity of Methanolic extract of Ricinus communis leaves (MERCL) was assayed through DPPH and H 2 O 2 free radical scavenging activity. Qualitative and quantitative analysis of MERCL using HPLC, demonstrated that Rutin was found to be predominant bioactive compound in the extract. Hepatitis was induced by treating the rats with D-GalN at a single intraperitoneal dose of 800 mg/kg.bw. Serum markers viz, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP) and Malondialdehyde (MDA) levels were significantly increased and the activity levels of antioxidant enzymes such as Superoxide dismutase (SOD),Catalase (CAT), Glutathione reductase (GR), Glutathione peroxidase (GPx), non-enzymatic antioxidant Glutathione (GSH) levels were decreased in the liver of hepatitis induced rats when compared to controls. Pre and post treatment with MERCL significantly altered the enzyme activities, GSH and MDA to normal levels. Histopathological observations also showed protective and curative effects of MERCL against D-GalN intoxication. These results demonstrated that MERCL significantly protected the liver from d -galactosamine induced hepatitis, improved the curative effect in the liver and hence, MERCL can be used as a potent hepatoprotective drug in future.

RNA-binding motif 6 (RBM6) is one of the most potent Lung cancer target proteins in humans. Variations in the expression of two genes such as G15/LUCA15/RBM5 and G16/RBM6/DEF3/NYLU12 show considerable sequence homology to each other in lung cancer cell lines and normal lung tissue. The present study reports construction of basic 3D model of RBM6 protein computationally using Wurst threading server and Modellar 9v7. Further, the developed initial model of the protein was subjected to molecular dynamics simulations using NAMD2.5 software with CHARMM27 force field, TIP 3p model of water, and the energy of structure was minimized with 10,000 steps with integrative time set of 2 ps. The final resolved model reliability was assessed by PROCHECK through Ramachandran plot calculations, Verify3D, and WHATCHECK programs. The Structure Based Virtual Screening was performed with selective 667 NSAIDs drugs from ZINC database against active site of RBM6 using Autodock vina in PyRx Virtual screening tool. The docking results reveal that the compounds ZINC59462883, ZINC59462879, and ZINC 28100170 have −11.2, −10.9, and −10.6 kcal/mol binding affinity, respectively, with RBM6. Through the interaction analysis, it was found that, the binding site residues viz. Ser75, His164, Arg215, Ser216, Arg217, Arg219, Ser279, Glu282, Thr303, and Arg306 were conserved in the interaction of RBM6 with various NSAIDs.

Recombinant baculovirus expressing insect-selective neurotoxins derived from venomous animals are considered as an attractive alternative to chemical insecticides for efficient insect control agents. Recently we identified and characterized a novel lepidopteran-selective toxin, Buthus tamulus insect-selective toxin (ButaIT), having 37 amino acids and eight half cysteine residues from the venom of the South Indian red scorpion, Mesobuthus tamulus. The synthetic toxin gene containing the ButaIT sequence in frame to the bombyxin signal sequence was engineered into a polyhedrin positive Autographa californica nuclear polyhedrosis virus (AcMNPV) genome under the control of the p10 promoter. Toxin expression in the haemolymph of infected larvae of Heliothis virescens and also in an insect cell culture system was confirmed by western blot analysis using antibody raised against the GST-ButaIT fusion protein. The recombinant NPV (ButaIT-NPV) showed enhanced insecticidal activity on the larvae of Heliothis virescens as evidenced by a significant reduction in median survival time (ST50) and also a greater reduction in feeding damage as compared to the wild-type AcMNPV.

The use of toxins as novel molecular probes to study the structure-function relationship of ion-channels and receptors as well as potential therapeutics in the treatment of wide variety of diseases is well documented. The high specificity and selectivity of these toxins have attracted a great deal of interest as candidates for drug development. This review highlights the involvement of the proteins and peptide toxins as well as non-proteinaceous compounds derived from both venomous and non-venomous animals, in anti-nociception and anti-inflammation. The possible mechanisms of these potential therapeutic agents and possible clinical applications in the treatment of pain and inflammation are also summarized.

Neurodegeneration induced by excitatory neurotransmitter glutamate is considered to be of particular relevance in several types of acute and chronic neurological impairments ranging from cerebral ischaemia to neuropathological conditions such as motor neuron disease, Alzheimer's, Parkinson's disease and epilepsy. The hyperexcitation of glutamate receptors coupled with calcium overload can be prevented or modulated by using well-established competitive and non-competitive antagonists targeting ion/receptor channels. The exponentially increasing body of pharmacological evidence over the years indicates potential applications of peptide toxins, due to their exquisite subtype selectivity on ion channels and receptors, as lead structures for the development of drugs for the treatment of wide variety of neurological disorders. This review comprehensively highlights the overview of the diversity in the molecular as well as neurobiological mechanisms of different peptide toxins derived from venomous animals with particular reference to neuroprotection. In addition, the potential applications of peptide toxins in the diagnosis and treatment of neurological disorders such as neuromuscular disorders, epilepsy, Alzheimer's and Parkinson's diseases, gliomas and ischaemic stroke and their future prospects in the diagnosis as well as in the therapy are addressed.

In the modern era, Epilepsy is one of the most prevalent serious neurological disorders, affecting 0.5 to 1.0% of the world’s population. Epileptic seizures are paroxysmal clinical events arising from neuronal hyper-excitability and hypersynchrony of the cerebral cortex, either locally (partial seizures) or diffusely in both hemispheres (generalized seizures). The agitated neuronal activity that occurs during a seizure is caused by a sudden imbalance between the inhibitory and excitatory signals in the brain with glutamate, ?-aminobutyric acid (GABA), noradrenaline, serotonin, and dopamine. Since long term usage of antiepileptic 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 Epilepsy. Keeping in view of relative importance of natural medicinal plants, the present study is mainly focused to characterize the anti-convulsant effect of Bacopa monnieri (BM), an Indian herb which is being extensively used in Ayurvedic treatments related to neurological complications. The present study was designed to assess the neurotoxicity of PTZ on the metabolism of Biogenic amines (Nor-epinephrine, Epinephrine, Dopamine, Serotonin) in different brain regions (Cerebral cortex, Cerebellum, Pons medulla and Hippocampus) of rat and explore the possible antiepileptic effect of different extracts (Ethanol, n-Hexane, Chloroform, Ethyl acetate, n-Butanol and Aqueous extracts) of BM in comparison with Diazepam (DZ) (Reference control). PTZ-Induced epilepsy caused significant decrease in all the catecholamine levels in all brain regions. On par with Diazepam pretreatment, different extracts of BM except aqueous extract (AE) significantly increased the monoamine contents in all the regions of brain. Mono amine oxidase (MAO) activity levels showed elevation in different brain regions of rat during PTZ-induced epilepsy which was reversed in epileptic animals pretreated with different extracts except AE and DZ. These findings suggest that BM causes perceptible changes in the biogenic amine metabolism as one of the major facets of its anticonvulsant activity. Hence, BM extract can be effectively used in the treatment of Epilepsy and other related neurological disorders.

The present study was aimed at investigating the therapeutic efficacy of vitamin E on oxidative injury in brain and liver of Newcastle disease virus (NDV) challenged chickens. We have analyzed the xanthine oxidase (XOD) activity; uric acid (UA) levels and superoxide radical generation by using electron spin resonance spectroscopy. Further, protein oxidation, nitration and apoptosis were evaluated in the brain and liver of the control, NDV-infected and NDV+Vit. E treated groups. A significant elevation was observed in XOD activity and UA levels in brain (p

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.