Oleuropein as a Potent Compound against Neurological Complications Linked with COVID-19: A Computational Biology Approach.

The association of COVID-19 with neurological complications is a well-known fact, and researchers are endeavoring to investigate the mechanistic perspectives behind it. SARS-CoV-2 can bind to Toll-like receptor 4 (TLR-4) that would eventually lead to α-synuclein aggregation in neurons and stimulation of neurodegeneration pathways. Olive leaves have been reported as a promising phytotherapy or co-therapy against COVID-19, and oleuropein is one of the major active components of olive leaves. In the current study, oleuropein was investigated against SARS-CoV-2 target (main protease 3CLpro), TLR-4 and Prolyl Oligopeptidases (POP), to explore oleuropein potency against the neurological complications associated with COVID-19. Docking experiments, docking validation, interaction analysis, and molecular dynamic simulation analysis were performed to provide insight into the binding pattern of oleuropein with the three target proteins. Interaction analysis revealed strong bonding between oleuropein and the active site amino acid residues of the target proteins. Results were further compared with positive control lopinavir (3CLpro), resatorvid (TLR-4), and berberine (POP). Moreover, molecular dynamic simulation was performed using YASARA structure tool, and AMBER14 force field was applied to examine an 100 ns trajectory run. For each target protein-oleuropein complex, RMSD, RoG, and total potential energy were estimated, and 400 snapshots were obtained after each 250 ps. Docking analyses showed binding energy as -7.8, -8.3, and -8.5 kcal/mol for oleuropein-3CLpro, oleuropein-TLR4, and oleuropein-POP interactions, respectively. Importantly, target protein-oleuropein complexes were stable during the 100 ns simulation run. However, an experimental in vitro study of the binding of oleuropein to the purified targets would be necessary to confirm the present study outcomes.

Dual-targeting potential of active constituents of Nigella sativa against FimH and CTX-M-15: A plausible therapeutic strategy against drug-resistant uropathogenic strains.

Uropathogenic strains belonging to the Enterobacteriaceae family are considered one of factors for urinary tract infections, and type 1 pilus fimbrial adhesin (FimH) and beta lactamase CTX-M-15 play crucial roles in their pathogenesis and resistance. Thus, a promising approach is to explore dual-targeting therapeutic agents that act against both FimH and CTX-M-15. In the present study, active constituents of Nigella sativa were selected on the basis of significant activity against UTIs. Molecular docking was used to target active constituents of Nigella sativa to the active sites of FimH and CTX-M-15; these included thymoquinone, dithymoquinone, carvacrol, p-cymene, thymol, thymohydroquinone and longifolene. Dithymoquinone was found to be the most potent dual inhibitor, with binding energy of -7.01 and -5.38kcal/mol against CTX-M-15 and FimH, respectively; In addition, Dithymoquinone exhibited superior activity compared to positive controls avibactam and heptyl α-D-mannopyranoside. Further molecular dynamic simulation studies were carried out to assess the stability of dithymoquinone-target protein complexes via RMSD, Rg, SASA, hydrogen bond number, and RMSF analysis. Both protein-ligand complexes were conserved and attained equilibrium at around 2.0 to 2.5 ns during 10 ns runs. These results suggest that active constituents of Nigella sativa, particularly dithymoquinone, might represent a plausible therapeutic strategy against resistant uropathogenic bacteria.

Mechanistic Insights into the Antimicrobial Actions of Metallic Nanoparticles and Their Implications for Multidrug Resistance.

Multiple drug-resistant bacteria are a severe and growing public health concern. Because relatively few antibiotics have been approved over recent years and because of the inability of existing antibiotics to combat bacterial infections fully, demand for unconventional biocides is intense. Metallic nanoparticles (NPs) offer a novel potential means of fighting bacteria. Although metallic NPs exert their effects through membrane protein damage, superoxide radicals and the generation of ions that interfere with the cell granules leading to the formation of condensed particles, their antimicrobial potential, and mechanisms of action are still debated. This article discusses the action of metallic NPs as antibacterial agents, their mechanism of action, and their effect on bacterial drug resistance. Based on encouraging data about the antibacterial effects of NP/antibiotic combinations, we propose that this concept be thoroughly researched to identify means of combating drug-resistant bacteria.

Silver nanoparticles from leaf extract of Mentha piperita: Eco-friendly synthesis and effect on acetylcholinesterase activity.

Silver nanoparticles (AgNPs) have been used in various medicinal and commercial products because of their exceptional anti-microbial and anti-odor properties. On the other hand, increased commercialization of AgNPs containing products has led to its release into the environment. Thus, studies are needed to assess their impact on the environment as well as on human body. Several reports have shown that AgNPs could cause some serious neurotoxic effects. Most of these studies have been performed using chemically synthesized AgNPs. In contrast, green nanoparticles are usually considered safer than their chemically synthesized counterparts. Accordingly, in this research work, we have assessed the effect of AgNPs synthesized from aqueous-leaf-extract of Mentha piperita on one of the most important neurological enzymes i.e. acetylcholinesterase (AChE) to predict its neurotoxicity. M. piperita synthesized AgNPs were subjected to characterization by UV-visible-spectrometry, Scanning Electron-Microscopy as well as Transmission Electron-Microscopy. Here, the size of the AgNPs was found to be 35 nm with spherical shape. These AgNPs showed concentration-dependent inhibitory-effect on the AChE enzyme-activity displaying an IC50 of 150 nM. Further, kinetic analysis showed mixed type of inhibition, which means that AgNPs were capable of binding to both the free enzyme (AChE) and to the enzyme-substrate (AChE-acetylcholine) complex. These results suggest that even green synthesized AgNPs might cause neurotoxicity via inhibiting AChE activity. However, more studies are needed to elucidate the exact mechanism of neurotoxicity by AgNPs. Nevertheless, we could safely state that the present study provides relevant preliminary information regarding neurotoxicity of green synthesized AgNPs.

Preclinical Hepatoprotective Effect of Herbalism Against Ethanol Induced Hepatotoxicity: A Review.

BACKGROUND: Liver ailments including alcoholic liver disease (ALD), still remain the main reason for morbidity & mortality worldwide. In fact, ALD is a multifactorial disease with complex pathophysiology which is linked to several types of liver damages including steatohepatitis, fibrosis and cirrhosis. METHODS: This review emphasizes on 30 herbal medicinal plants with their extracts studied for protective effect against ALD and current scientific evidence of ALD cure by thirty Indian Materia Medica including Tilia Platyphyllos, Amomum subulatum, Carica papaya, Pogostemon patchouli, Commelina benghalensis, Bacopamonnieri, Pecan nut, Allium cepa, Beta Vulgaris, Adina cordifolia, Ocimum gratissimum, Vernonia amygdalina, Sida veronicaefolia, Chenopodium album, Korean red ginseng, Elephantopus scaber, Tecomella undulata, Prunus armeniaca, Sea tangle (Laminaria japonica), Emblica officinalis, Saccharum officinarum, Cocculus hirsutus, Cassia roxburghii, Zhi-Zi-Da- Huang, Phyllanthus amarus, Aegle marmelos, Agrimonia eupatoria, Flaveria trinervia, Curcuma longa and Garcinia indica. RESULTS: Reduction in oxidative stress, improvement in inflammation, reduction in degeneration of fat and necrosis are some of the mechanisms of action of these medicinal plants observed in alcohol induced in-vivo and in-vitro liver injury models. CONCLUSION: Accordingly, this review provides several evidences which show that these medicinal plants could be used for the treatment and prevention of ALD.

Synthesis and Characterization of Cefotaxime Conjugated Gold Nanoparticles and Their Use to Target Drug-Resistant CTX-M-Producing Bacterial Pathogens.

Multidrug-resistance due to "ß lactamases having the expanded spectrum" (ESBLs) in members of Enterobacteriaceae is a matter of continued clinical concern. CTX-M is among the most common ESBLs in Enterobacteriaceae family. In the present study, a nanoformulation of cefotaxime was prepared using gold nanoparticles to combat drug-resistance in ESBL producing strains. Here, two CTX-M-15 positive cefotaxime resistant bacterial strains (i.e., one Escherichia coli and one Klebsiella pneumoniae strain) were used for testing the efficacy of "cefotaxime loaded gold-nanoparticles." Bromelain was used for both reduction and capping in the process of synthesis of gold-nanoparticles. Thereafter, cefotaxime was conjugated onto it with the help of activator 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide. For characterization of both unconjugated and cefotaxime conjugated gold nanoparticles; UV-Visible spectroscopy, Scanning, and Transmission type Electron Microscopy methods accompanied with Dynamic Light Scattering were used. We used agar diffusion method plus microbroth-dilution method for the estimation of the antibacterial-activity and determination of minimum inhibitory concentration or MIC values, respectively. MIC values of cefotaxime loaded gold nanoparticles against E. coli and K. pneumoniae were obtained as 1.009 and 2.018 mg/L, respectively. These bacterial strains were completely resistant to cefotaxime alone. These results reinforce the utility of conjugating an old unresponsive antibiotic with gold nanoparticles to restore its efficacy against otherwise resistant bacterial pathogens. J. Cell. Biochem. 118: 2802-2808, 2017. © 2017 Wiley Periodicals, Inc.

Comparative Inhibition Study of Compounds Identified in the Methanolic Extract of Apamarga Kshara Against Trichomonas vaginalis Carbamate Kinase (TvCK): An Enzoinformatics Approach.

In the present study, we have identified ten compounds, namely dodecanol acid, myristic acid, neophytadiene, palmitic acid, heptadecanoic acid, linoleic acid, elaidic acid, 3-7-dimethyl acid, stearic acid and methyl eicos acid, of the methanolic extract of Apamarga Kshara by GC-MS analysis. Apamarga Kshara has been reported to be active against cervical erosion. Major causal organism for cervical erosion is Trichomonas vaginalis. However, there is a paucity of information about the mechanism of action and inhibitory effect of the biologically active natural compounds presented in A. Kshara against this organism (T. vaginalis). Therefore, present investigation was conducted to observe possible interactions of these compounds on T. vaginalis carbamate kinase using molecular docking software 'AutoDock 4.2.' Identification of the amino acid residues crucial for the interaction between T. vaginalis carbamate kinase and these natural compounds is of due scientific interest. The study will aid in efficacious and safe clinical use of the above-mentioned compounds.

Magnetic Nanoparticles: Properties, Synthesis and Biomedical Applications.

Importance of magnetic nanoparticles in daily life including biomedical applications in near future cannot be overlooked. This review focuses on the properties of magnetic nanoparticles (MNPs), various approaches for their synthesis, and their biomedical applications. First part of this review focuses on the classes, physical properties, and characteristics of MNPs. The second part sheds light on strategies developed for the synthesis of MNPs, with special attention given to biological, physical, and chemical approaches as well as recent modifications in the preparation of monodispersed samples. Furthermore, this review deals with the biomedical applications of MNPs, which includes applications in targeted drug delivery, diagnostics, gene therapy, hyperthermia and advantages in the field of medicine.