R software for QSAR analysis in phytopharmacological studies.

INTRODUCTION: In recent decades, quantitative structure-activity relationship (QSAR) analysis has become an important method for drug design and natural product research. With the availability of bioinformatic and cheminformatic tools, a vast number of descriptors have been generated, making it challenging to select potential independent variables that are accurately related to the dependent response variable. OBJECTIVE: The objective of this study is to demonstrate various descriptor selection procedures, such as the Boruta approach, all subsets regression, the ANOVA approach, the AIC method, stepwise regression, and genetic algorithm, that can be used in QSAR studies. Additionally, we performed regression diagnostics using R software to test parameters such as normality, linearity, residual histograms, PP plots, multicollinearity, and homoscedasticity. RESULTS: The workflow designed in this study highlights the different descriptor selection procedures and regression diagnostics that can be used in QSAR studies. The results showed that the Boruta approach and genetic algorithm performed better than other methods in selecting potential independent variables. The regression diagnostics parameters tested using R software, such as normality, linearity, residual histograms, PP plots, multicollinearity, and homoscedasticity, helped in identifying and diagnosing model errors, ensuring the reliability of the QSAR model. CONCLUSION: QSAR analysis is vital in drug design and natural product research. To develop a reliable QSAR model, it is essential to choose suitable descriptors and perform regression diagnostics. This study offers an accessible, customizable approach for researchers to select appropriate descriptors and diagnose errors in QSAR studies.

Identifying druggable targets from active constituents of Azadirachta indica A. Juss. for non-small cell lung cancer using network pharmacology and validation through molecular docking.

INTRODUCTION: Azadirachta indica A. Juss. is a well-known medicinal plant that has been used traditionally to cure various ailments in every corner of the globe. There are many in vitro and in vivo experimental evidences in connection with the bioactivity of the extracts of this plant. Lung cancer is the deadliest form of cancer and contributes to the most cancer related deaths. The mode of action of anticancer components of this plant is still to be established explicitly. OBJECTIVE: The objective of this study is to identify druggable targets of active constituents of A. indica A. Juss. for non-small cell lung cancer (NSCLC) using network pharmacology and validation of activity through molecular docking analysis. METHODOLOGY: Targets of all the active phytochemicals from A. indica were predicted and genes related to NSCLC were retrieved. A protein-protein interaction (PPI) network of the overlapping genes were prepared. Various databases and servers were employed to analyse the disease pathway enrichment analysis of the clustered genes. Validation of the gene/protein activity was achieved by performing molecular docking, and ADMET profiling of selected phytocompounds was performed. RESULT: Gene networking revealed three key target genes as EGFR, BRAF and PIK3CA against NSCLC by the active components of A. indica. Molecular docking and ADMET analysis further validated that desacetylnimbin, nimbandiol, nimbin, nimbinene, nimbolide, salannin and vepinin are the best suited anti- NSCLC among all the phytocompounds present in this plant. CONCLUSION: The present study has provided a better understanding of the pharmacological effects of active components from A. indica and its potential therapeutic effect on NSCLC.

Protective Effects of Pelargonidin against DMBA-Induced Mammary Tumorigenesis in BALB/c Mice through Reduced Oxidative Stress and Lipid Anomalies.

Among luminal types of breast cancers, ER + breast cancer is the most frequently diagnosed cancer globally. ER + breast cancer is commonly treated with SERM drugs that block ER to prevent ER-mediated cancerous growth. Our previous computational screening found pelargonidin (PG) can inhibit ER-signaling with potent bioactivity and satisfactory toxicological features. The present study explored the anti-tumoral prospect of PG against DMBA-induced ER + murine mammary carcinogenesis. The female BALB/c mice were divided into control (A) and DMBA-exposed groups. Following tumor appearance, the DMBA-exposed group was divided into five groups: tumor control, PG-treated (Groups P25, P50, and P100), and tamoxifen-treated (TAM). The results indicated that PG-treatment dose-dependently reduced the mean tumor volume, reinstated body weight loss, and enhanced the percentage survival of tumor-bearing mice. In addition, we recorded a significant reduction in LPO, total cholesterol, and triglycerides and a surge in the activity of antioxidases and phase II detoxifying enzymes in PG-treated animals. PG also dose-dependently increased the serum level of unbound estradiol, an indicator of competitive ER binding by an ER agonist/antagonist. These data suggest that pelargonidin has potent anticancer potential against the animal model of ER + breast cancer that matches the efficiency of tamoxifen with conceivably fewer side effects.

Acteoside (Verbascoside): A Prospective Therapeutic Alternative against Hepatocellular Carcinoma by Inhibiting the Expression of AXL, FGFR, BRAF, TIE2 and RAF1 Targets.

AIM: Hepatocellular carcinoma (HCC) is the world's second leading cause of cancerrelated mortality and the fifth most prevalent cancer overall. Several synthetic and plant-based remedies are in practice to treat diverse liver disorders. Because of their minimal side effects and protective characteristics, plant phenolics have the potential to become alternative therapeutics, replacing currently existing HCC medications. The present study identifies the plant phenolics as having the capacity to inhibit HCC with low side effects and cost efficiency. BACKGROUND: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality, despite the proven effectiveness of screening programs for at-risk individuals, the majority of patients have disease progression or tumor characteristics that preclude curative therapies at the time of diagnosis. Acteoside (Verbascoside) is a naturally occurring phenylethanoid glycoside found throughout the plant kingdom. Acteoside is a physiologically active chemical with the number of pharmacological and protective effects against various liver illnesses. OBJECTIVES: Currently used HCC medications have a variety of side effects. Plant-based chemicals offer the possibility of treating HCC with minimal side effects. The work is targeted to find the best phytochemical (plant phenolic) lead molecule for future drug development research against Hepatocellular carcinoma. METHODS: The targets were selected based on an analysis of relevant literature, and the 3D structures of the selected receptors were obtained in. pdb format from the RCSB-Protein data bank (PDB, http://www.rscb.org/pdb). Based on a review of the literature, sixty plant secondary metabolites, or plant phenolics, were selected. The ligand structures were obtained and downloaded in.sdf format from the NCBI PubChem chemicals database (https://pubchem.ncbi.nlm.nih.gov/). Molecular docking between the receptor and ligands was accomplished using the Molegro Virtual Docker 6.0 (MVD) software. RESULTS: The target RAF1, BRAF chain 1, TIE2 chain 2 FGFR1, FGFR2, AXL, and FGFR4 showed the best binding effectiveness with acteoside compared to their respective positive control. RET chain 1 and BRAF chain 2 acteoside showed prominent binding efficacy after Curcumin, and Epigallocatechingallate, respectively, against positive control. Present findings clearly point towards the potentiality of acteoside in inhibiting various HCC targets. CONCLUSION: Acteoside may be used as a prominent lead molecule in the future treatment of hepatic cancer with its multifaceted binding efficiencies against various target proteins.

Natural Flavonoids in the Prevention and Treatment of Lung Cancer: A Pharmacological Aspect.

Deadly disease cancer has many types; among them, lung cancer is responsible for the highest number of cancer mortality. Existing therapies as well as drugs for treating lung cancer are not effective and are often associated with innumerable side effects and toxicities. For these reasons, researchers have been working on developing novel anti-cancer medicines from plants and other natural sources that have a high safety profile. Natural flavonoids are a polyphenolic group of phytochemicals extracted from plants and other plant-derived compounds. Natural flavonoids are gaining popularity due to their unique and priceless medicinal properties, including anticancer properties. Several researchers have already declared that flavonoids possess the ability to treat different cancers, particularly lung cancer. The bioactivity of natural flavonoids is mainly due to their structural diversity. Natural flavonoids fight against lung cancer by regulating redox homeostasis, upregulating apoptosis, pro-apoptotic factors, and survival genes, arresting cell cycle progression, autophagy, reducing cell proliferation and invasiveness, maintaining inflammation response, downregulating anti-apoptotic factors, and targeting lung cancer signaling pathways. Flavonoids can act alone or synergistically with other agents to treat lung cancer. Due to these reasons, it is possible to use natural flavonoids as pharmaceutical leads to prevent and treat lung cancer.

Hibiscus sabdariffa anthocyanins are potential modulators of estrogen receptor alpha activity with favourable toxicology: a computational analysis using molecular docking, ADME/Tox prediction, 2D/3D QSAR and molecular dynamics simulation.

The estrogen hormone receptor (ER) mediated gene expression mainly regulate the development and physiology of the primary and secondary reproductive system alongside bone-forming, metabolism and behaviour. Over-expressed ER is associated with several pathological conditions and play a crucial role in breast cancer occurrence, progression and metastasis. Hibiscus sabdariffa L. or roselle is a rich source of naturally occurring polyphenolic compounds that reportedly have robust estrogenic activity. However, the estrogen-like ingredient of the plant remains ambiguous. This study has screened a library of already recorded and less-explored compounds of Hibiscus sabdariffa for their estrogen receptor binding affinity and safety using a suite of computational methods that include protein-ligand docking, ADME and Toxicity prediction, and 2D/3D QSAR. The study revealed that the estrogen-receptor binding potential of Pelargonidin, Delphinidin, Cyanidin, and Hibiscetin are more efficient than popular breast cancer drugs, Tamoxifen and Raloxifene. Besides, the compounds exhibited favourable toxicological parameters with potent bioactivity towards binding ER-α subunit. Thus, these compounds can serve as prototypes for designing novel Selective Estrogen Receptor Modulator molecules with a few structural modifications. This is the first report exploring the phytochemical basis of estrogenic activity of Hibiscus sabdariffa L.Communicated by Ramaswamy H. Sarma.

Ethnomedicinal, Phytochemical and Nutra-pharmaceutical Potentials of Indian Arrowroot (Curcuma angustifolia Roxb).

Indian Arrowroot (Curcuma angustifolia Roxb) belonging to the Zingiberaceae family is widely distributed in India and some parts of Nepal, Thailand, Bangladesh and Pakistan. It is traditionally used as medicine for treating various diseases and also used as food. Few data are available about its application in pharmacology and therapeutics. Literature search for related contents, keywords such as "Curcuma angustifolia Roxb", "traditional food", "ethnomedicine", "pharmacology", "phytochemicals", "pharmacological activities" were used in search engines including PubMed, Google Scholar, Scopus, ScienceDirect, and Semantic Scholar. Secondary metabolites found in Indian Arrowroot include essential oils, alkaloids, flavonoids, terpenoids, phytosterols, terpenes, phenols, and others. Pharmacological activities such as antioxidant, antiinflammatory, anti-proliferative, anti-ulcerogenic, hepatoprotective, and anti-cancerous activities have been shown by Indian Arrowroot (Curcuma angustifolia Roxb). The presence of nutritional value and pharmaceutical potential gained demand in the various food production industries and pharmacology research. It may play a vital role in future studies of Curcuma angustifolia Roxb as ethnomedicine and further exploitation in pharmacological studies.

Transcriptomic Analysis Revealed Reactive Oxygen Species Scavenging Mechanisms Associated With Ferrous Iron Toxicity in Aromatic Keteki Joha Rice.

Lowland acidic soils with water-logged regions are often affected by ferrous iron (Fe2+) toxicity, a major yield-limiting factor of rice production. Under severe Fe2+ toxicity, reactive oxygen species (ROS) are crucial, although molecular mechanisms and associated ROS homeostasis genes are still unknown. In this study, a comparative RNA-Seq based transcriptome analysis was conducted to understand the Fe2+ toxicity tolerance mechanism in aromatic Keteki Joha. About 69 Fe homeostasis related genes and their homologs were identified, where most of the genes were downregulated. Under severe Fe2+ toxicity, the biosynthesis of amino acids, RNA degradation, and glutathione metabolism were induced, whereas phenylpropanoid biosynthesis, photosynthesis, and fatty acid elongation were inhibited. The mitochondrial iron transporter (OsMIT), vacuolar iron transporter 2 (OsVIT2), ferritin (OsFER), vacuolar mugineic acid transporter (OsVMT), phenolic efflux zero1 (OsPEZ1), root meander curling (OsRMC), and nicotianamine synthase (OsNAS3) were upregulated in different tissues, suggesting the importance of Fe retention and sequestration for detoxification. However, several antioxidants, ROS scavenging genes and abiotic stress-responsive transcription factors indicate ROS homeostasis as one of the most important defense mechanisms under severe Fe2+ toxicity. Catalase (CAT), glutathione (GSH), ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), and glutathione reductase (GR) were upregulated. Moreover, abiotic stress-responsive transcription factors, no apical meristem (NAC), myeloblastosis (MYB), auxin response factor (ARF), basic helix-loop-helix (bZIP), WRKY, and C2H2-zinc finger protein (C2H2-ZFP) were also upregulated. Accordingly, ROS homeostasis has been proposed as an essential defense mechanism under such conditions. Thus, the current study may enrich the understanding of Fe-homeostasis in rice.

Antibacterial activity of curcumin and its essential nanoformulations against some clinically important bacterial pathogens: A comprehensive review.

Multidrug-resistant bacterial infections can kill 700,000 individuals globally each year and is considered among the top 10 global health threats faced by humanity as the arsenal of antibiotics is becoming dry and alternate antibacterial molecule is in demand. Nanoparticles of curcumin exhibit appreciable broad-spectrum antibacterial activity using unique and novel mechanisms and thus the process deserves to be reviewed and further researched to clearly understand the mechanisms. Based on the antibiotic resistance, infection, and virulence potential, a list of clinically important bacteria was prepared after extensive literature survey and all recent reports on the antibacterial activity of curcumin and its nanoformulations as well as their mechanism of antibacterial action have been reviewed. Curcumin, nanocurcumin, and its nanocomposites with improved aqueous solubility and bioavailability are very potential, reliable, safe, and sustainable antibacterial molecule against clinically important bacterial species that uses multitarget mechanism such as inactivation of antioxidant enzyme, reactive oxygen species-mediated cellular damage, and inhibition of acyl-homoserine-lactone synthase necessary for quorum sensing and biofilm formation, thereby bypassing the mechanisms of bacterial antibiotic resistance. Nanoformulations of curcumin can thus be considered as a potential and sustainable antibacterial drug candidate to address the issue of antibiotic resistance.

Molecular docking analysis of flupenthixol and desmethylastemizole with the apoptotic regulator proteins CFLAR and TRAF2 linked to lung carcinoma.

It is known that molecular changes in apoptotic genes due to mutation may cause disruption of apoptotic pathway resulting in an abrupt increase in cell proliferation. Therefore, it is of interest to identify compounds that could potentially replenish the changes in the apoptotic pathway, resulted from mutation. The gene network analysis using the Network Analyzer Plugin of Cytoscape (3.5.1) shows CFLAR and TRAF2 as influential genes in the apoptotic pathway. Mutation in these genes brings loss in apoptotic property of a cell and thus increases the cell proliferating activity. Thus, data on the molecular docking analysis of four natural compounds from Ottelia alismoides (L.) Pers with the two target proteins were reported. Flupenthixol and desmethylastemizole was found to be two efficient ligand molecules based on ligand-target interaction. In stereochemical quality assessment, the Ramachandran plot analysis of receptors indicates the better stereochemical characteristics for receptor-ligand interaction.

Systematics, Phytochemistry, Biological Activities and Health Promoting Effects of the Plants from the Subfamily Bombacoideae (Family Malvaceae).

Plants belonging to the subfamily Bombacoideae (family Malvaceae) consist of about 304 species, many of them having high economical and medicinal properties. In the past, this plant group was put under Bombacaceae; however, modern molecular and phytochemical findings supported the group as a subfamily of Malvaceae. A detailed search on the number of publications related to the Bombacoideae subfamily was carried out in databases like PubMed and Science Direct using various keywords. Most of the plants in the group are perennial tall trees usually with swollen tree trunks, brightly colored flowers, and large branches. Various plant parts ranging from leaves to seeds to stems of several species are also used as food and fibers in many countries. Members of Bombacoides are used as ornamentals and economic utilities, various plants are used in traditional medication systems for their anti-inflammatory, astringent, stimulant, antipyretic, microbial, analgesic, and diuretic effects. Several phytochemicals, both polar and non-polar compounds, have been detected in this plant group supporting evidence of their medicinal and nutritional uses. The present review provides comprehensive taxonomic, ethno-pharmacological, economic, food and phytochemical properties of the subfamily Bombacoideae.

Anti-MRSA Constituents from Ruta chalepensis (Rutaceae) Grown in Iraq, and In Silico Studies on Two of Most Active Compounds, Chalepensin and 6-Hydroxy-rutin 3',7-Dimethyl ether.

Ruta chalepensis L. (Rutaceae), a perennial herb with wild and cultivated habitats, is well known for its traditional uses as an anti-inflammatory, analgesic, antipyretic agent, and in the treatment of rheumatism, nerve diseases, neuralgia, dropsy, convulsions and mental disorders. The antimicrobial activities of the crude extracts from the fruits, leaves, stem and roots of R. chalepensis were initially evaluated against two Gram-positive and two Gram-negative bacterial strains and a strain of the fungus Candida albicans. Phytochemical investigation afforded 19 compounds, including alkaloids, coumarins, flavonoid glycosides, a cinnamic acid derivative and a long-chain alkane. These compounds were tested against a panel of methicillin-resistant Staphylococcus aureus (MRSA) strains, i.e., ATCC 25923, SA-1199B, XU212, MRSA-274819 and EMRSA-15. The MIC values of the active compounds, chalepin (9), chalepensin (10), rutamarin (11), rutin 3'-methyl ether (14), rutin 7,4'-dimethyl ether (15), 6-hydroxy-rutin 3',7-dimethyl ether (16) and arborinine (18) were in the range of 32-128 µg/mL against the tested MRSA strains. Compounds 10 and 16 were the most active compounds from R. chalepensis, and were active against four out of six tested MRSA strains, and in silico studies were performed on these compounds. The anti-MRSA activity of compound 16 was comparable to that of the positive control norfloxacin (MICs 32 vs 16 µg/mL, respectively) against the MRSA strain XU212, which is a Kuwaiti hospital isolate that possesses the TetK tetracycline efflux pump. This is the first report on the anti-MRSA property of compounds isolated from R. chalepensis and relevant in silico studies on the most active compounds.

Transcriptional expression of secondary resistance genes ccdB and repA2 is enhanced in presence of cephalosporin and carbapenem in Escherichia coli.

BACKGROUND: The issue of carbapenem resistance in E.coli is very concerning and it is speculated that cumulative effect of both primary resistance genes and secondary resistance genes that act as helper to the primary resistance genes are the reason behind their aggravation. Therefore, here we attempted to find the role of two secondary resistance genes (SRG) ccdB and repA2 in carbapenem resistance in E. coli (CRE). In this context influential genes belonging to secondary resistome that act as helper to the primary resistance genes like blaNDM and blaCTX-M in aggravating ß-lactam resistance were selected from an earlier reported in silico study. Transcriptional expression of the selected genes in clinical isolates of E.coli that were discretely harboring blaNDM-1, blaNDM-4, blaNDM-5, blaNDM-7 and blaCTX-M-15 with and without carbapenem and cephalosporin stress (2 µg/ml) was determined by real time PCR. Cured mutants sets that were lacking (i) primary resistance genes, (ii) secondary resistance genes and (iii) both primary and secondary resistance genes were prepared by SDS treatment. These sets were then subjected to antibiotic susceptibility testing by Kirby Bauer disc diffusion method. RESULTS: Out of the 21 genes reported in the in silico study, 2 genes viz. repA2 and ccdB were selected for transcriptional expression analysis. repA2, coding replication regulatory protein, was downregulated in response to carbapenems and cephalosporins. ccdB, coding for plasmid maintenance protein, was also downregulated in response to carbapenems except imipenem and cephalosporins. Following plasmid elimination assay increase in diameter of zone of inhibition under stress of both antibiotics was observed as compared to uncured control hinting at the reversion of antibiotic susceptibility by the-then resistant bacteria. CONCLUSION: SRGs repA2 and ccdB help sustenance of blaNDM and blaCTX-M under carbapenem and cephalosporin stress.

Conjugation of micro/nanocurcumin particles to ZnO nanoparticles changes the surface charge and hydrodynamic size thereby enhancing its antibacterial activity against Escherichia coli and Staphylococcus aureus.

Nanobiotechnology-mediated synthesis of ZnO nanoparticles, micro/nanocurcumin, and curcumin-ZnO nanocomposites and their characterization followed by comparative study of their antibacterial, antioxidant, and iron-chelating efficiency at various dosages are discussed. Micro/nanocurcumin and ZnO nanoparticles were synthesized using curcumin and zinc nitrate as precursor and then conjugated by sonication to synthesize curcumin-ZnO nanocomposites. The synthesized nanoparticles were then characterized by using ultraviolet-visible spectroscopy, X-ray diffraction, Scanning electron microscopy, Fourier-transform infrared spectroscopy, and dynamic light scattering analysis. After that, the antibacterial activity of the synthesized nanoparticles was evaluated by the optical density (OD600 ) method against Escherichia coli and Staphylococcus aureus cells. The DPPH (2,2-diphenyl-1-picrylhydrazyl ), hydroxyl radical scavenging activity, and ferrous ion-chelating efficiency of synthesized nanoparticles were evaluated by spectrophotometry analysis. Nanocurcumin (mean zeta potential = -25 mV; average hydrodynamic diameter = 410 nm) based coating of ZnO nanoparticles (mean zeta potential = -15.9 mV; average hydrodynamic diameter = 274 nm) to synthesize curcumin-ZnO nanocomposites (mean zeta potential = -18.8 mV; average hydrodynamic diameter = 224 nm) exhibited enhanced zeta potential, which resulted in reduced agglomeration, smaller hydrodynamic size in water, improved aqueous solubility, and dispersion. All the aforesaid factors including the synergistic antibacterial effect of ZnO nanoparticle and micro/nanocurcumin contributed to increased antibacterial efficiency of curcumin-ZnO nanocomposites. Micro/nanocurcumin due to its better water solubility and small hydrodynamic diameter exhibited enhanced antioxidant and ferrous ion-chelating efficiency than curcumin.

Naturally Occurring Calanolides: Occurrence, Biosynthesis, and Pharmacological Properties Including Therapeutic Potential.

Calanolides are tetracyclic 4-substituted dipyranocoumarins. Calanolide A, isolated from the leaves and twigs of Calophyllum lanigerum var. austrocoriaceum (Whitmore) P. F. Stevens, is the first member of this group of compounds with anti-HIV-1 activity mediated by reverse transcriptase inhibition. Calanolides are classified pharmacologically as non-nucleoside reverse transcriptase inhibitors (NNRTI). There are at least 15 naturally occurring calanolides distributed mainly within the genus Calophyllum, but some of them are also present in the genus Clausena. Besides significant anti-HIV properties, which have been exploited towards potential development of new NNRTIs for anti-HIV therapy, calanolides have also been found to possess anticancer, antimicrobial and antiparasitic potential. This review article provides a comprehensive update on all aspects of naturally occurring calanolides, including their chemistry, natural occurrence, biosynthesis, pharmacological and toxicological aspects including mechanism of action and structure activity relationships, pharmacokinetics, therapeutic potentials and available patents.

Cyathea gigantea (Cyatheaceae) as an antimicrobial agent against multidrug resistant organisms.

BACKGROUND: Rapid emergence of multidrug resistant (MDR) organisms in hospital and community settings often result into treatment failure, thus leading the clinicians with fewer treatment options. Cyathea gigantea, an ethnomedicinally important fern used in cuts and wound infections. So, if this medicinal plant is used in treating the MDR infections then it might bring certain relief in future treatment options. METHODS: Antibacterial activity of C. gigantea against MDR bacteria was assed using well diffusion and broth microdilution methods to determine the diameters of growth inhibition zones, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Synergistic activity was also determined with the conventional antibiotics by disc diffusion method followed by FIC index of each of the tested antibiotic was calculated. The active extract was then subjected to fractionation by column chromatography and antibacterial activity was done with each of the collected fractions. RESULTS: Crude extract of C. gigantea was found to be active against all the tested organisms. The MIC was 200 µg/ml against Gram-positive i.e., Staphylococcus aureus ATCC 25923 and 400 µg/ml against Gram-negative i.e., Escherichia coli ATCC 25922 and Pseudomonas aeruginosa PAO1, while the MBC was 400 µg/ml in case of Gram-positive and 800 µg/ml for Gram-negative. The synergistic activity revealed that the plant extract increased the antibacterial property of the studied antibiotics and the FIC index showed that significant synergistic activity was shown by ciprofloxacin followed by tetracycline, ampicillin and oxacillin. Antibacterial activity with the fractionated extract showed that the FR II, FR III and FR IV were active against both Gram-positive and Gram-negative bacteria, whereas FR I, FR V and FR VI did not show antibacterial property against any of the tested bacteria. CONCLUSIONS: Extracts of C. gigantea was found active against both selected Gram-positive and Gram-negative organisms and thus offers the scientific basis for the traditional use of the fern. The present study also provides the basis for future study to validate the possible use against multidrug resistant organisms.

Role of Natural Phenolics in Hepatoprotection: A Mechanistic Review and Analysis of Regulatory Network of Associated Genes.

The liver is not only involved in metabolism and detoxification, but also participate in innate immune function and thus exposed to frequent target Thus, they are the frequent target of physical injury. Interestingly, liver has the unique ability to regenerate and completely recoup from most acute, non-iterative situation. However, multiple conditions, including viral hepatitis, non-alcoholic fatty liver disease, long term alcohol abuse and chronic use of medications can cause persistent injury in which regenerative capacity eventually becomes dysfunctional resulting in hepatic scaring and cirrhosis. Despite the recent therapeutic advances and significant development of modern medicine, hepatic diseases remain a health problem worldwide. Thus, the search for the new therapeutic agents to treat liver disease is still in demand. Many synthetic drugs have been demonstrated to be strong radical scavengers, but they are also carcinogenic and cause liver damage. Present day various hepatic problems are encountered with number of synthetic and plant based drugs. Nexavar (sorafenib) is a chemotherapeutic medication used to treat advanced renal cell carcinoma associated with several side effects. There are a few effective varieties of herbal preparation like Liv-52, silymarin and Stronger neomin phages (SNMC) against hepatic complications. Plants are the huge repository of bioactive secondary metabolites viz; phenol, flavonoid, alkaloid etc. In this review we will try to present exclusive study on phenolics with its mode of action mitigating liver associated complications. And also its future prospects as new drug lead.

Expansion of highly stable bla OXA-10 ß-lactamase family within diverse host range among nosocomial isolates of Gram-negative bacilli within a tertiary referral hospital of Northeast India.

BACKGROUND: The current study reports dissemination of highly stable bla OXA-10 family of beta lactamases among diverse group of nosocomial isolates of Gram-negative bacilli within a tertiary referral hospital of the northern part of India. METHODS: In the current study, a total number of 590 Gram negative isolates were selected for a period of 1 year (i.e. 1st November 2011-31st October 2012). Members of Enterobacteriaceae and non fermenting Gram negative rods were obtained from Silchar Medical College and Hospital, Silchar, India. Screening and molecular characterization of ß-lactamase genes was done. Integrase gene PCR was performed for detection and characterization of integrons and cassette PCR was performed for study of the variable regions of integron gene cassettes carrying bla OXA-10. Gene transferability, stability and replicon typing was also carried out. Isolates were typed by ERIC as well as REP PCR. RESULTS: Twenty-four isolates of Gram-negative bacilli that were harboring bla OXA-10 family (OXA-14, and OXA16) with fact that resistance was to the extended cephalosporins. The resistance determinant was located within class I integron in five diverse genetic contexts and horizontally transferable in Enterobacteriaceae, was carried through IncY type plasmid. MIC values were above break point for all the tested cephalosporins. Furthermore, co-carriage of bla CMY-2 was also observed. CONCLUSION: Multiple genetic environment of bla OXA-10 in this geographical region must be investigated to prevent dissemination of these gene cassettes within bacterial population within hospital settings.

Carbapenem nonsusceptibility with modified OprD in clinical isolates of Pseudomonas aeruginosa from India.

This study was undertaken to investigate OprD porin-mediated carbapenem nonsusceptibility in clinical isolates of Pseudomonas aeruginosa from a tertiary referral hospital of Northeast India. A total of 267 nonduplicate, consecutive clinical isolates of P. aeruginosa were obtained. Mutation and expression levels of OprD gene were determined in carbapenem-nonsusceptible carbapenemase-nonproducing isolates. Among 19 carbapenem-nonsusceptible carbapenemase-nonproducing isolates, 11 of them demonstrated variable band pattern while performing denaturing gradient gel electrophoresis with amplified products of OprD gene. Sequencing of variable band products revealed three mutation patterns in three isolates. Relevant decrease in expression of OprD gene could also be observed in them. All the three isolates exhibited a higher minimum inhibitory concentration for imipenem (64-128 µg/mL) compared to meropenem (16-64 µg/mL). Inactivating mutation and decreased expression of OprD contribute mainly to imipenem resistance as well as to meropenem.

Molecular and in silico analysis of a new plasmid-mediated AmpC ß-lactamase (CMH-2) in clinical isolates of Klebsiella pneumoniae.

Two Klebsiella strains isolated from urine samples were positive for blaAmpC by PCR and showed sequence similarity with CMH-1 (98.6%) after sequencing. It also shares 82% similarity with ACT-1, 85% with MIR-1 and 81% with the chromosomal AmpC gene of Enterobacter cloacae. This gene was associated with the plasmid of IncK type. It has an open reading frame of 381 amino acid with four amino acid substitutions at position D144A, C189R, Q192E, and A195T as compared to CMH-1. When expressed in E.coli DH5α and E.coli strain B, this ß-lactamase conferred resistance to cefotaxime, ceftriaxone and ceftazidime. In addition, both in vitro and in silico analysis revealed that this cephalosporinase was inhibited by cefepime and carbapenem group of drugs. Therefore, this new plasmid-encoded AmpC type ß-lactamase gene was designated as CMH-2.