Search

Active herbal or natural compounds have high chemical diversity and specificity than synthetic drugs. Recently, we have validated the hypoglycemic salutation of Oncocalyx glabratus in rodent model, and demonstrated the activation of PPARα/γ by its newly ioslated flavan derivative Oncoglabrinol C (5,3′-Dihydroxyflavan 7-4′-O-digallate) in liver cells (HepG2). Here we evaluated the potential of Oncoglabrinol C against Dichlorofluorescin (DCFH) and Methylglyoxal (MGO) induced endothelial cells (HUVEC) oxidative and apoptotic damage, including activation of PXR-mediated hepatic CYP3A4. Our MTT assay showed protection of ~57% and ~63.5% HUVEC cells by 10 and 20 μg/ml doses of Oncoglabrinol C, respectively through attenuating DCFH triggered free-radicals. Also, the two doses effectively protected ~53% and ~65.5% cells, respectively by reversing MGO toxicity. In DCFH and MGO treated cells, Oncoglabrinol C (20 μg/ml) effectively downregulated caspase 3/7 activity by ~33% and ~43.5%, respectively. Moreover, in reporter gene (dual-luciferase) assay, Oncoglabrinol C (20 μg/ml) moderately activated hepatic CYP3A4. Molecular docking of Oncoglabrinol C indicated its strong interactions with cellular caspase 3/7, PPARα/γ and PXR proteins, which supported its anti-apoptotic (antagonistic) as well as pro-hypoglycemic and PXR/CYP activating (agonistic) activities. Taken together, our findings demonstrated the potential of Oncoglabrinol C in reversing the endothelial oxidative and apoptotic damage as well as in the activation of hepatic CYP3A4. This warrants further evaluations of Oncoglabrinol C and related compounds towards developing effective and safe drugs against diabetes associated cardiovascular disorders.

Oligonucleotide/oligosaccharide-binding fold (OB-fold) plays a major role in the regulation of central dogma of life via binding though DNA and RNA. The OB-fold domains are diverse in nature and present in large number of proteins with verities of molecular functions. Here, we have investigated the distribution of sequence, structure and repeats of cold shock DNA-binding proteins (CSDB), a member of OB-fold, in all three kingdoms to establish functional relationships. The CSDB is consists of 30 domains with a major contribution of S1 (>110,601 sequences), S12 (>23,760 sequences), S17 (>14,833 sequences) and S28e (>1615 sequence) domains. These domains are largely found in bacteria (70-90%). The number of S1 domain repeats in eukaryota varies from 1 to 15 and are well-correlated with the protein size. The molecular function analysis suggests that a large number of repeats in the S1 domain are involved in diverse molecular functions in bacteria and eukaryotes. In-depth structure analysis of S1, S12, S17 and S28e domain-containing proteins of the OB-fold family provides a reasonable basis to understand the relationship of size and number of repeats with the corresponding molecular functions.

Despite high anti-HBV efficacies, while the nucleoside analogs (e.g., lamivudine) lead to the emergence of drug-resistance, interferons (e.g., IFN-α causes adverse side-effects. Comparatively, various natural or plant products have shown similar or even better efficacy. Hence, new antiviral strategies must focus not only on synthetic molecules but also on potential natural compounds. In this report, we have combined the in vitro cell culture and in silico molecular docking methods to assess the novel anti-HBV activity and delineate the inhibitory mechanism of selected plant-derived pure compounds of different classes. Of the tested (2.5-50 μg/ml) twelve non-cytotoxic compounds, ten (10 μg/ml) were found to maximally inhibit HBsAg production at day 5. Compared to quercetin (73%), baccatin III (71%), psoralen (67%), embelin (65%), menisdaurin (64%) and azadirachtin (62%) that showed high inhibition of HBeAg synthesis, lupeol (52%), rutin (47%), β-sitosterol (43%) and hesperidin (41%) had moderate efficacies against HBV replication. Further assessment of quercetin in combination with the highly active compounds, enhanced its anti-HBV activity up to 10%. Being the most important drug target, a 3-D structure of HBV polymerase (Pol/RT) was modeled and docked with the active compounds, including lamivudine as standard. Docking of lamivudine indicated strong interaction with the modeled HBV Pol active-site residues that formed stable complex (∆G = −5.2 kcal/mol). Similarly, all the docked antiviral compounds formed very stable complexes with HBV Pol (∆G = −6.1 to −9.3 kcal/mol). Taken together, our data suggest the anti-HBV potential of the tested natural compounds as novel viral Pol/RT inhibitors. : Keywords, Hepatitis B virus, Antiviral, HBV polymerase, Natural compounds, Molecular docking, Pol/RT inhibitors

Elevation in hyperglycemia-associated methylglyoxal level can trigger vascular endothelial cells oxidative stress and apoptosis. The present work assesses the cell proliferative, anti-oxidative and anti-apoptotic potential of

The iron transporter protein, Transferrin (Tf), is a glycoprotein that binds and mediates the Iron (Fe) transport through blood plasma. It has a significant role in transporting Fe in the endosomal compartment of the cells by forming complexes of Fe-Tf-TfR (Transferrin receptor). The role of Tf in Alzheimer's disease (AD) pathogenesis is not so clear and needs to be explored, but it has been linked to the activity of Cyclooxygenase-2 (COX-2) in rats with diabetic neuropathy. Galantamine is a moderate inhibitor of Acetylcholinesterase (AChE) isolated from Galanthus woronowii. Here we have explored the possible interactions of Tf and Galantamine using computational as well as experimental approaches. First, we have performed molecular docking of Galantamine with Tf to predict their binding affinity and possible interactions. The molecular docking study was further escorted by all-atom molecular dynamics (MD) simulations for 100 ns followed by principal component analysis (PCA). MD studies suggested that the Tf-Galantamine docked complex is stable throughout the simulation trajectory. The computational results were further entrenched by a fluorescence-based binding study that suggested moderate binding of Galantamine with Tf with a binding constant (K) of 104 M−1. Isothermal titration calorimetry (ITC) further validated the spontaneous binding of Galantamine to Tf. This study provides a platform and can be implicated in AD therapy.

Increasing manufacturing and use of nanoparticles in industrial and biomedical applications creates the necessity to understand the impact of the interaction of nanoparticles with biomacromolecules. In the present study, graphene oxide nanosheets (GONS) were synthesized using modified Hummer's method and further characterized employing X-ray diffraction (XRD), UV, FTIR, and Raman spectroscopy. After characterization, the interaction of GONS with human serum albumin (HSA) was investigated to delineate the binding mechanism employing different kinds of spectroscopic techniques. Intrinsic fluorescence spectroscopy revealed that complex formation is taking place between HSA and GONS. Fluorescence-based binding studies suggested that GONS binds to HSA with a significant binding affinity, and the interaction is governed by dynamic quenching. The evaluation of enthalpy change (ΔH) and entropy change (ΔS) suggested that the HSA-GONS complex formation is driven by hydrogen bonding and van der Waals interaction and hence complexation process is seemingly specific. Structural transition in the microenvironment of HSA was monitored using synchronous fluorescence spectroscopy and three-dimensional fluorescence spectroscopy, which showed that GONS binding to HSA influences the microenvironment around tyrosine and tryptophan residues. Secondary structural alterations in HSA upon binding to GONS were measured using circular dichroism (CD) spectroscopy. Additionally, molecular docking provided an insight into the critical residues involved in HSA-GONS interaction and further validated our in vitro observations affirming interaction between GONS and HSA. The significance of this study is attributable to the fact that HSA and GONS can be used as nanocarriers in drug delivery systems.

Bovine liver catalase (BLC), a homotetramer (Mr = 28,000), is an industrially and pharmaceutically important enzyme. A cationic Gemini surfactant (tetramethylene-1,4-bis(dimethyltetradecylammonium bromide); 14-4-14) was found to induce aggregation in BLC, as confirmed by Rayleigh light scattering and dynamic light scattering up to ∼150 μM, at a critical micellar concentration (CMC) at physiological pH. On further increasing, the Gemini concentration aggregate disappeared. Secondary and tertiary structural studies confirmed that BLC structure perturbation occurs in two phases: first, loss of both secondary and tertiary structures till the CMC of 14-4-14; and second, recovery of the secondary structure above the CMC, unlike the tertiary structure that showed further solvent accessibility of tryptophan residues, which resulted in unfolding. Moreover, 14-4-14 may have unfolded the enzyme by either directly interacting or opening the hydrophobic patches or engineering solvent shells and reversibly disrupting helical structures until the concentration reaches the CMC. However, above the CMC, with the probable steric hindrance in 14-4-14 active groups due to polymerization, the BLC secondary structure recovered. The thioflavin T fluorescence and transmission electron microscopy results showed that the aggregates were amyloid in nature. Molecular docking analysis also confirmed that 14-4-14 interacted with BLC mainly through hydrophobic interactions, along with a minor contribution of electrostatic interactions. Thus, this study showed how to reverse the surfactant induced BLC amyloid at physiological pH and 298 K, which could be exploited industrially.