Strong Molecular Interactions Research Articles

Scopoletin: Antiamyloidogenic, Anticholinesterase, and Neuroprotective Potential of a Natural Compound Present in Argyreia speciosa Roots by In Vitro and In Silico Study.

Alzheimer’s disease (AD) is characterized by depositions of amyloid β (Aβ) peptides aggregates resulting in plaques formation in the central nervous system (CNS). This study evaluates the disease-modifying potential of scopoletin against multiple factors associated with AD such as cholinesterase enzymes, Aβ peptides, and neuroprotective properties against Aβ- and H2O2-induced cytotoxicity under in vitro conditions. Scopoletin was identified and quantified using UPLC-QTOF (ultra-high performance liquid chromatography-quadrupole time-of-flight) and high-performance liquid chromatography (HPLC), respectively. The antiamyloidogenic potential was evaluated by thioflavin T and congo red binding assay. Inhibition of key enzymes, that is, acetylcholinesterase and butyrylcholinesterase, was investigated by Ellman’s assay. UPLC-QTOF analysis showed that most abundant phytoconstituent present in Argyreia speciosa hydroalcoholic root extract was scopoletin followed by festuclavine and ergometrine. Scopoletin was further quantified using novel reverse phase (RP)-HPLC method developed in this study. The neuroprotective potential of scopoletin was found to be 69% against Aβ42-induced neurotoxicity and 73% against H2O2-induced cytotoxicity in PC12 cell culture at 40 μM final concentration. At the same concentration, scopoletin inhibited Aβ42 fibril formation up to 57%. The IC50 concentration for AChE and BuChE enzyme inhibition by scopoletin was 5.34 and 9.11 μM, respectively. The antiaggregation and enzyme inhibition results were complemented with strong molecular interactions of scopoletin with target proteins validated by in silico molecular docking analysis. Based on this study, it can be concluded that scopoletin can be used as a lead for amelioration of symptoms and disease-modifying effects in AD.

Computational screening of promising beta-secretase 1 inhibitors through multi-step molecular docking and molecular dynamics simulations - Pharmacoinformatics approach

Alzheimer’s disease (AD) is a neurodegenerative disorder generally developed with aging. AD slowly hammers the memory and cognitive abilities which eventually leads to abnormal behaviour, and ultimately left with disability and dependency. It is anticipated that by the year 2050, world population will experience the incidence of 100 million AD cases. It has been more than hundred years passed since AD recognized as a dreadfull disease, but there is no effective curative agent discovered against AD to date. One of the major hallmarks of the AD development is the accumulation of extracellular amyloid-beta (Aβ) plaques in the brain. In the amyloidogenic process, an extensively studied beta-secretase enzyme, known as BACE1, plays a key role in the accumulation and production of Aβ fragments. Therefore, successful inhibition of BACE1 by small molecular chemical entities can be an effective approach for anti-AD drug development. Hence, the current study has been perceived to find out potential BACE1 inhibitiors by virtual screening of entire Asinex chemical library database through multi-step molecular docking methodologies. Further, sequential screening of in-silico pharmacokinetics, molecular dynamic (MD) simulations analyses along with binding free energy estimation were performed. Comparative analyses and characteristics of molecular binding interactions assessment finally suggests that five molecules (B1–B5) to be the most promising BACE1 inhibitors. Molecular interactions analyses revealed that either one or both the catalytic dyad residues (Asp32 and Asp228) of BACE1 has formed strong molecular interactions with all the proposed molecules. Not only the catalytic dyad residues are involved in the formation of molecular binding interactions but also other important non-Asp binders residues such as Gly34, Tyr71, Trp115, Arg128, Lys224, Gly230, Thr231, Thr232, Arg235, Thr329, and Val332 found to interact with the selected compounds. Moreover, the dynamic behaviour of proposed molecules and BACE1 was explored through all-atoms MD simulation study for 100 ns time span. Analysis of MD simulation trajectories explained that all identified molecules are efficient enough to retain the structural and molecular interactions integrity inside the receptor cavity of BACE1 in dynamic environment. Finally, the binding free energy of each molecule has calculated from MD simulation trajectories through MM-PBSA method and found that all molecules possess a strong binding affinity towards the BACE1. The high negative binding free energies are found to be within the range of −994.978 to −561.562 kJ/mol for the identified compounds. Henceforth, analyses of extensively studied multi-cheminformatics approaches explained that proposed molecules might be promising BACE1 inhibitors for therapeutic application in AD, subjected to experimental validation.

Reversible Bioadhesives Using Tannic Acid Primed Thermally‐Responsive Polymers

AbstractA two‐layer approach is reported for the formation of a thermally triggered reversible adhesive, involving a thermally‐responsive polymer matrix coated on tannic acid‐pretreated substrates/tissues. Interfacial adhesion originates from strong molecular interactions of tannic acid with both the polymer matrix and the substrate/tissue. The reversibility is due to a temperature‐triggered phase transition of the polymer matrix, leading to cohesive failure. Depending on different gelation mechanisms, the polymer forms a highly cohesive gel or soft solid upon either warming or cooling, leading to a strong adhesion to the tissues at physiological temperatures. Detachment of the adhesive is triggered by a temperature‐induced compromise of cohesive strength of the polymer matrix, by the opposite gel‐to‐sol transition. This facile, low‐cost, and modular design offers a reversible adhesive platform which is useful for biomedical and industrial applications.

Zwitterionic impetus on single lithium-ion conduction in solid polymer electrolyte for all-solid-state lithium-ion batteries

Single lithium-ion conducting solid polymer electrolytes (SLICSPEs) with high ionic conductivity play critical roles in pursuit of efficient and safe energy storage. Herein, we presented a universal and facile strategy towards high-performance SLICSPEs by applying representatively monomeric or polymeric zwitterions as synergistic ion dissociator and phase plasticizer for expedited single Li+ conduction in solid polymer matrix. It is manifested that the strong molecular interactions between zwitterions and SLICSPEs effectively facilitate the disintegration of Li+ from polyanionic backbone, while the impregnation of zwitterions simultaneously reduces the PEO crystallinity and increases the flexibility of EO segments, thus cooperatively promoting the Li+ mobility within the solid polymer matrix without expense of ion selectiveness. Attributed to these unique features, the as-developed SLICSPE achieved a considerable ionic conductivity of 8.39 × 10−5 S/cm at 90 °C without uptake of any organic solvents, as well as a high Li+ transference number approximately to unity, which further powered the decent cyclability and rate capability of the corresponding LiFePO4/SLICSPE/Li batteries, demonstrating a good promise in advancing the development of all-solid-state lithium ion batteries.

Thermodynamics and solute-solvent interactions of lovastatin in an aqueous arginine solution

Lovastatin (LVS) is an effective therapeutic and prophylactic agent in several cardiovascular disorders. However, it has low bioavailability. This study investigated solute-solvent and solute-cosolute interactions and assessed thermodynamic parameters that contributed to LVS solubility enhancement in the presence of arginine (ARG) as a hydrotropic agent. The electrolytic conductance of LVS-ARG binary system was measured at temperatures from 298.15 K to 313.15 K. Conductometric parameters such as limiting molar conductance was evaluated. Additionally, thermodynamic parameters (ΔG0, ΔH0, ΔS0 and ES) involved in the association process of the solute in the aqueous solution of ARG solution were determined systematically. Solubility markedly improved 43-fold in the LVS-ARG complex compared to LVS alone. The analysed data from values of molar conductance and activation energy suggested favourable solubilisation, with a stronger solute-solvent interaction between LVS-ARG in water at higher temperatures. ARG and LVS complexation caused by strong molecular interactions was confirmed by spectral results. Hence, the addition of ARG as a co-solute was proven to enhance LVS solubility in water. The obtained data will ultimately enable the development of desired highly soluble, more efficient and safer LVS preparations.

One-pot synthesis of hierarchical magnetic porous γ-Fe2O3@NiFe2O4 composite with solid-phase morphology changes promoted by adsorption of anionic azo-dye

Hierarchical magnetic porous γ-Fe2O3@NiFe2O4 composite was synthesized in air by sol-gel auto-combustion method. Through nitrogen physisorption analysis was found a very large surface area of 220 m2/g. Due to the strong molecular host-guest interaction, complemented by the noticeable magnetic properties (Ms = 25 emu/g and Hc = 137 Oe), γ-Fe2O3@NiFe2O4 shows outstanding adsorption performance over anionic dyes, including but not limited to methyl orange. The adsorption process is spontaneous and the pseudo-second-order kinetic model and the Langmuir isotherm model well described the adsorption process. Unquestionably, the excellent adsorption capacity of MO azo dye of 1.66 g/g, according to Langmuir isotherm, promotes morphology changes from porous-like material to fibrous-like structure. The inherent features of morphology changes enhance the photocatalytic activity of the composite by increasing the surface exposure to the visible light. Compared with previously published data, the adsorption capacity of γ-Fe2O3@NiFe2O4 ranks at the top.

Cross-linked beta alumina nanowires with compact gel polymer electrolyte coating for ultra-stable sodium metal battery

Sodium metal batteries have potentially high energy densities, but severe sodium-dendrite growth and side reactions prevent their practical applications, especially at high temperatures. Herein, we design an inorganic ionic conductor/gel polymer electrolyte composite, where uniformly cross-linked beta alumina nanowires are compactly coated by a poly(vinylidene fluoride-co-hexafluoropropylene)-based gel polymer electrolyte through their strong molecular interactions. These beta alumina nanowires combined with the gel polymer layer create dense and homogeneous solid-liquid hybrid sodium-ion transportation channels through and along the nanowires, which promote uniform sodium deposition and formation of a stable and flat solid electrolyte interface on the sodium metal anode. Side reactions between the sodium metal and liquid electrolyte, as well as sodium dendrite formation, are successfully suppressed, especially at 60 °C. The sodium vanadium phosphate/sodium full cells with composite electrolyte exhibit 95.3% and 78.8% capacity retention after 1000 cycles at 1 C at 25 °C and 60 °C, respectively.

Adsorption of Fluoroquinolone Antibiotics at the Gas-Liquid Interface Using Ionic Surfactants.

The overuse of antibiotics in today's society has resulted in high concentrations of pharmaceutical contaminants in the natural environment. In this work, we investigated the surfactant-mediated adsorption of fluoroquinolone (FQ) antibiotics at the gas-liquid interface and their separation using a semi-batch foam fractionation process. FQs being a zwitterionic compound have an affinity to bind with both cationic and anionic surfactants. The adsorption of FQs to the gas-liquid interface was investigated using a cationic cetyltrimethylammonium bromide (CTAB) and anionic sodium dodecyl sulfate (SDS) surfactant. Ciprofloxacin (CF) was chosen as a model FQ antibiotic. The adsorption properties of the surfactant systems and CF were characterized using pendant-drop tensiometry and surface excess analysis. It was found that CF partitions to the gas-liquid interface more readily in the presence of SDS compared to CTAB. This was also corroborated in the foam fractionation experiments. At optimum operating conditions, CF showed a higher removal efficiency with SDS (96.3%) compared to CTAB (52%). In spite of strong molecular interactions between CTAB and CF, the preferential adsorption of DS--CF complexes was far greater than CTA+-CF complexes. At optimized operating conditions, using SDS as the surfactant, other FQs such as norfloxacin, levofloxacin, and ofloxacin were recovered up to 97.9, 91.7, and 96.7%, respectively, with effluent concentration less than 100 nM. Overall, the work demonstrates foam fractionation as a novel and environment-friendly gas-liquid separation technique for the targeted removal of FQ antibiotics from waterbodies.

Screening of terpenoids as potential therapeutics against Zaire ebolavirus infection through pharmacophore-based drug design

Backgroud: Ebola virus disease (EVD) has spread to various countries in the world and has caused many deaths. Five different virus species can cause EVD, but the most virulent is Zaire ebolavirus (EBOV). The genome of EBOV includes seven genes that encode proteins playing essential roles in the virus lifecycle. Among these proteins, VP24 plays a vital role in the inhibition of the host cells’ immune system. Therefore, VP24 is a potential target for EVD therapy. In the present study, a potential inhibitor of EBOV VP24 activity was identified through pharmacophore-based drug design. Methods: This research was a in silico study, using pharmacophore based molecular docking simulation to obtain inhibitor candidates. Result: Terpenoids were used as VP24 inhibitor candidates. In particular, 55,979 terpenoids were obtained from the PubChem database. An initial screening based on the toxicity prediction test was performed with DataWarrior software: 3,353 ligands were shown to have a favorable toxicity profile, but only 1,375 among them had suitable pharmacophore features. These ligands were used for pharmacophore-based rigid and flexible molecular docking simulations with PDB ID: 4M0Q, chosen as the crystal structure of EBOV VP24. Six ligands predicted to have strong molecular interactions with EBOV VP24 underwent pharmacological property analysis through various software packages, including DataWarrior, SwissADME, admetSAR, pkCSM, and Toxtree. Conclusions: Taxumairol V was identified as the best candidate for EVD drug therapy via EBOV VP24 inhibition based on its molecular properties, predicted molecular interactions with the target molecule, and predicted pharmacological properties.

Thermodynamic solubility and solvation behavior of ferulic acid in different (PEG-400 + water) binary solvent mixtures

This work was carried out to determine solubility, solution thermodynamics, solvation behavior, and molecular interactions of a natural compound ferulic acid (FLA) in different ‘[polyethylene glycol-400 (PEG-400) + water]’ binary solvent mixtures at ‘T = 298.2 K to 318.2 K’ and ‘p = 0.1 MPa.’ The mole fraction solubilities (xe) of FLA were determined by liquid chromatographic technique using a static equilibrium technique. The obtained solubility data of FLA were regressed using ‘Van’t Hoff, Apelblat, Yalkowsky-Roseman and Jouyban-Acree models.’ The solubility of FLA (expressed in mole fraction) was enhanced with elevation in absolute temperature in each ‘PEG-400 + water’ binary solvent mixture evaluated. The maximum xe values of FLA were recorded in neat PEG-400 (1.94 × 10−1) at ‘T = 318.2 K.’ While, the minimum one was obtained in neat water (4.90 × 10−5) at ‘T = 298.2 K.’ The molecular interactions between FLA-PEG-400 and FLA-water were obtained by determination of activity coefficients of FLA in different ‘PEG-400 + water’ binary solvent mixtures. The physical data of activity coefficients recorded in this work suggested strong molecular interactions in FLA-PEG-400 in comparison with FLA-water. ‘Apparent thermodynamic analysis’ suggested an ‘endothermic and entropy-driven dissolution’ of FLA in each ‘PEG-400 + water’ binary solvent mixture investigated.

The antidiabetic properties of the hot water extract of kola nut (Cola nitida (Vent.) Schott & Endl.) in type 2 diabetic rats

Ethnopharmacological relevanceCola nitida is amongst the evergreen plants native to West Africa used in the treatment of various ailments including diabetes.Aim of the study: This study aims to investigate the antidiabetic effects of the hot water extract of C. nitida seeds in type 2 diabetic rats. MethodsType 2 diabetic rats were orally administered with low (150 mg/kg bw) and high (300 mg/kg bw) doses of the hot water extract for 6 wk and thereafter, blood glucose, insulin level, lipid profile, pancreatic β-cell function, perfusion and morphology, redox imbalance, glycolytic and cholinergic enzymes, as well as of caspase-3 and Nrf2 expressions were measured. ResultsTreatment with the extract led to significant depletion of blood glucose, serum triglycerides, LDL-cholesterol, fructosamine, ALT, and uric acids, while elevating serum insulin and HDL-cholesterol levels. The infusion also significantly (p < 0.05) elevated GSH level, SOD, catalase, α-amylase, and ATPase activities, with concomitant depletion of myeloperoxidase enzyme activity, and NO and MDA levels in the serum and pancreas. Significantly (p < 0.05) improved pancreatic β-cell function and morphology were observed in rats treated with C. nitida, with restored pancreatic capillary networks. C. nitida inhibited the activities of glycogen phosphorylase, fructose 1,6 biphosphatase, glucose 6 phosphatase, and acetylcholinesterase while downregulated the Nrf2 expression. NMR analysis of the extract revealed the presence of caffeine and theobromine. The molecular docking studies indicated that identified compounds displayed strong molecular interactions with caspase-3 and Nrf2. ConclusionThese results insinuate the antidiabetic activities of C. nitida hot water extract and may be attributed to the NMR-identified compounds.

Molecular Interactions in Solutions of 1,1-Bis(4-(2-oxopropoxy)phenyl)cyclohexane on Ultrasonic Velocity, Density, and Viscosimetric Data

The ultrasonic velocity, density, and viscosity are measured at various concentrations 0.1–0.01 mol dm–3 in the solutions of 1,1-bis(4-(2-oxopropoxy)phenyl)cyclohexane (BMAPC) in 1,4-dioxane (DO), ethyl acetate (EA), tetrahydrofuan (THF) at 298–313 K and at atmospheric pressure. Parameters: acoustical impedance, adiabatic compressibility, Rao’s molar sound function, Van der Waals constant, internal pressure, free volume, intermolecular free path length, classical absorption coefficient and viscous relaxation time, Gibbs free energy of activation, enthalpy of activation and entropy of activation were determined. Change of the parameters with T indicated existence of strong molecular interactions in solutions and further supported by positive values of solvation number. Gibbs free energy of activation decrease linearly with increasing C and T in the DO system while it decreases with C and increase with T in EA and THF. Enthalpy and entropy of activation were found to be slightly concentration dependent.

Effect of Drug-Polymer Interactions through Hypromellose Acetate Succinate Substituents on the Physical Stability on Solid Dispersions Studied by Fourier-Transform Infrared and Solid-State Nuclear Magnetic Resonance.

The present study evaluated the specific intermolecular interactions between carbamazepine (CBZ) and substituents of hypromellose acetate succinate (HPMC-AS), as well as the mechanism of inhibition of recrystallization of solid dispersions (SDs) using Fourier-transform infrared (FTIR) and solid-state nuclear magnetic resonance (NMR) spectroscopy. CBZ and HPMC derivatives, including HPMC, hypromellose acetate (HPMC-A), and hypromellose succinate (HPMC-S), were spray-dried to prepare CBZ/polymer spray-dried samples (SPDs). CBZ/HPMC SPD and CBZ/HPMC-A SPD recrystallized within 10 days at 60 °C and 0% relative humidity, whereas CBZ/HPMC-S SPD maintained its amorphous state for a longer period. FTIR and solid-state NMR measurements using 13C cross polarization (CP), 1H single-pulse, and 1H-15N CP-based heteronuclear single quantum correlation filter experiment with very fast magic angle spinning (MAS) at 70 kHz identified molecular interactions in CBZ/polymer SPDs. Although the HPMC backbone and substituents did not interact notably with CBZ and disrupt CBZ-CBZ intermolecular interactions (formed in the amorphous CBZ), acetate and succinate substituents on HPMC-A and HPMC-S disrupted CBZ-CBZ intermolecular interactions through formation of CBZ/polymer interactions. The acetate substituent formed a hydrogen bond with the NH2 group of CBZ, whereas the succinate substituent formed molecular interactions with both the C═O and NH2 groups of CBZ. Formation of relatively strong molecular interactions between CBZ and the succinate substituent followed by disruption of CBZ-CBZ intermolecular interactions effectively stabilized the amorphous state of CBZ in CBZ/HPMC-S SPD. The correlation between CBZ-polymer interactions and ability of polymers to effectively inhibit CBZ recrystallization is reflected in various commercial HPMC-AS. For example, HPMC-AS LF grade, containing higher amounts of the succinate group, was found to effectively inhibit the recrystallization of CBZ through strong molecular interactions as compared with the HPMC-AS HF grade. The present study demonstrated that a detailed investigation of molecular interactions between the drug and the polymer using FTIR and solid-state NMR spectroscopy could contribute to a suitable selection of the SD carrier.

Unlocking the Lithium Storage Capacity of Aluminum by Molecular Immobilization and Purification

Aluminum is regarded as a promising alternative for graphite anode in next-generation lithium-ion batteries, but its application is hindered by the simultaneous presence of aluminum oxide and the huge volume changes. Herein, hydrogenation-induced self-assembly of robust Al nanocrystals with high purity that are uniformly anchored on graphene is demonstrated. The strong molecular interaction between Al and graphene can not only thermodynamically facilitate the homogenous distribution of Al on graphene but also effectively alleviate the volume changes and preserve the structural integrity of the electrode. More importantly, density functional theory calculations reveal that the absence of oxidation can lower the energy barrier for Li diffusion inside the Al matrix to less than 1/6 of that in an Al matrix with only one monolayer coverage of oxygen. These unique structural features enable the aluminum/graphene nanosheets (Al@GNs) electrode to realize a high reversible capacity of 1219 mAh g-1 and an excellent cycling stability with capacity of 766 mAh g-1 after 1000 cycles at the 3 A g-1 rate. Furthermore, a full cell, comprising an Al@GNs anode and LiFePO4 cathode, exhibits remarkable capacity retention of 96.4% after 100 cycles at the 0.5 A g-1 rate.

Physicochemical characterisation andin vitroStarch digestion of Avocado Seed Flour (Persea americana V. Hass) and its starch and fibrous fractions

SummaryThe avocado seed is considered a by‐product of their pulp exploitation and today it does not present relevant food or industrial applications. In this study, we evaluate the potential use of its flour, their isolated starch and fibre fractions. After processing, the flour yielded 46.28%, and showed 6.7% of protein and low fat and ash contents (3.4, and 2.71% respectively). The starch yielded 27.28% with low‐fibre content that influenced its viscosity properties; as well as their water absorption index (WAI), water solubility index (WSI) and oil absorption index (OAI), that were 2.43%, 11.22% and 0.16% respectively. Thein vitrostarch digestion of the different obtained fractions showed higher amounts of rapidly digestible starch (56.8%–75.36%, flour and starch respectively). The functional properties of the materials were correlated with strong molecular interactions with their apparently unique amylose structure; for this, this by‐product may have different potential for food applications.

Involvement of metabolism-permeability in enhancing the oral bioavailability of curcumin in excipient-free solid dispersions co-formed with piperine

Curcumin (CUR) has gained increasing interest worldwide due to multiple biological activities. However, the therapeutic application remains limited because of its low aqueous solubility, intestinal metabolism and poor membrane permeability. In present study, an excipient-free CUR solid dispersion co-formed with piperine (PIP), the absorption enhancer involving metabolism-permeability, was successfully prepared by melting and quench cooling (co-amorphous CUR-PIP). The co-amorphous CUR-PIP exhibited superior performance in non-sink dissolution compared with crystalline and amorphous CUR, and showed physically stable at least 3 months, attributing to the strong molecular interactions between CUR and PIP as evaluated by FTIR spectra. Furthermore, the combination of PIP with CUR in the co-amorphous formulation could inhibit the glucuronidation of CUR, as exhibited in the in vitro assay of rat intestinal microsomes. The co-amorphous CUR-PIP would also exhibit higher gastrointestinal membrane permeability of CUR, as confirmed by Papp of CUR in Caco-2 model. After administration of co-amorphous CUR-PIP, the AUC of CUR significantly increased by 2.16- and 1.92-fold those in crystalline and amorphous CUR, respectively. This study demonstrates that the developed co-amorphous CUR-PIP can enhance the bioavailability of CUR by increasing its dissolution, inhibiting metabolic processes, and facilitating membrane permeability.

Synthesis of novel thermosetting imide compounds having phenylethynyl carbonyl groups at both terminal ends and production of new network polymers based on the imide compounds

A novel thermosetting imide compound having a respective phenylethynyl carbonyl group at both terminal ends was newly synthesized from an acid anhydride having a phenylethynyl carbonyl group and various diamine compounds. The thermosetting behavior of the obtained novel thermosetting imide compound having phenylethynyl carbonyl groups was analyzed through differential scanning calorimetry measurements and infrared spectroscopic analysis. As a result, it became clear that a curing reaction of phenylethynyl carbonyl groups proceeds at approximately 200°C and that the curing reaction thereof proceeds at a temperature that is lower by 150°C or more compared with that of phenylethynyl groups. Examination of the polymerization reaction of the imide compounds having phenylethynyl carbonyl groups using model compounds revealed that a reaction that imparted an alkene C=C and polycyclic aromatic structure progressed. Moreover, a network polymer obtained from a thermosetting imide compound having respective phenylethynyl carbonyl groups at both terminal ends exhibited extremely superior heat resistance and thermal decomposition resistance. These superior thermal properties are thought to be due to the strong molecular interaction (molecular packing) that results from the polycyclic aromatic structures and alkenes produced through polymerization of the phenylethynyl carbonyl groups and to the suppression of the movement of the molecular chains.

Molecular modelling and simulation of fusion-based amorphous drug dispersions in polymer/plasticizer blends

A realistic molecular description of amorphous drug-polymer-plasticizer matrices, suitable for the preparation of amorphous solid dispersions (ASDs) with the aid of fusion-based techniques, was evaluated. Specifically, the incorporation of two model drugs (i.e. ibuprofen, IBU, and carbamazepine, CBZ) having substantially different thermal properties and glass forming ability, on the molecular representation of polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol graft copolymer (SOL)/polyethylene glycol (PEG, working as a plasticizer) molecular and thermal properties were evaluated with the aid of classical molecular dynamics (MD) and docking simulations. Results showed good agreement between molecular modelling estimations and experimentally determined properties. Specifically, the computed Tg values that resulted from MD simulations for IBU-SOL/PEG and CBZ-SOL/PEG (53.8 and 54.2 °C, respectively) were in reasonable agreement with the corresponding values resulting from differential scanning calorimetry (DSC) measurements (49.8 and 50.1 °C), while both molecular modelling and experimental obtained results suggested miscibility among system components. Additionally, interactions between CBZ and SOL observed during MD simulations were verified by FTIR analysis, while MD simulations of the hydration process suggested strong molecular interactions between IBU-SOL and CBZ-SOL.

Thermophysical Study of Binary Systems of tert-Amyl Methyl Ether with n-Hexane and m-Xylene

This work presents the experimentally determined density (ρ), viscosity (η), speed of sound (u), and surface tension (σ) data for tert-amyl methyl ether (TAME) + n-hexane and TAME + m-xylene systems at several temperatures (298.15, 308.15, 318.15, 323.15, and 328.15 K). These experimentally determined thermophysical data are utilized to compute various excess/deviation parameters such as molar volume (VE), isentropic compressibility (κsE), speed of sound (uE), deviation in viscosity (Δ ln η), isobaric thermal expansion coefficient (αPE), and surface tension (σE). The inspection of parameters response may interpret the existing specific molecular interactions as well as the mixing behavior of solutions. The critical analysis of observed parametric behavior have unveiled the strong and weak molecular interactions in TAME with m-xylene and TAME with n-hexane systems, respectively.

Oleander Stem and Root Standardized Extracts Mitigate Acute Hyperglycaemia by Limiting Systemic Oxidative Stress Response in Diabetic Mice.

The extracts of different parts of Nerium oleander L. are used as antidiabetic remedy in the traditional medicinal systems of different parts of the world. Despite these uses in ethnomedicinal system, the antihyperglycemic potentials of oleander stem (NOSE) and root (NORE) extracts have not been pharmacologically evaluated. Therefore, we aimed at evaluating the antidiabetic ethnomedicinal claims of NOSE and NORE, primarily focusing on glucose homeostasis and associated metabolic implications. Alloxan-treated mice with hyperglycaemia (blood glucose >200 mg/dL) were treated with oleander 70% hydromethanolic extracts (200 mg/kg) for 20 consecutive days, and the results were compared with positive control glibenclamide. Blood glucose level was 52–65% lowered (P < 0.001) in oleander treated groups, which was otherwise 4.62 times higher in diabetic mice, compared to control. Insulin resistance was lowered 51–36% irrespective of any significant (P > 0.05) changes in insulin sensitivity throughout the treatments. Improved serum insulin remained associated with lowered glucose level (r P = −0.847 and −0.772; P < 0.01). Markers of hyperglycaemia-related hepatic glycogen, glycated haemoglobin (HbA1c), hyperlipidaemia, hepatic injury, and diabetic nephropathy were normalized as well. Improvement of systemic intrinsic antioxidant enzymes (catalase and peroxidase) were correlated (r P = −0.952 to −0.773; P < 0.01) with lower lipid peroxidation by-product malondialdehyde (MDA) in the circulation. Principal component analysis coupled with hierarchical cluster analysis represented shift in metabolic homeostasis in diabetic mice, which was further normalized by oleander and glibenclamide treatment. Additionally, molecular docking studies of the phenolic acids measured by HPLC with intracellular cytoprotective transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) revealed strong molecular interactions. The results collectively support the ethnomedicine antidiabetic claims of oleander stem and root and suggest that the oleander mediated elevation of systemic antioxidant status is likely responsible for the improved glycaemic control.