Ethnomedicinal values of Boerhaavia diffusa L. as a panacea against multiple human ailments: a state of art review

Ethnopharmacological relevance: Therapeutic botanicals (plants and derivatives) are in use since antiquity for various health ailments. The ethnic community is the repository of the information, the multifactorial therapeutic applications of which may often need scientific validation. The spreading hogweed or Boerhaavia diffusa L., also known as Punarnava, is a reassuring medicinal herb with diverse pharmacological benefits. It is used in Ayurveda in Asia and Africa as a rejuvenator or “Rasayan” for its excellent antiaging and antioxidant properties.Aim: The study aimed at compiling the state-of-art knowledge of the medicinal benefits of Boerhaavia diffusa L. and unraveling the unexplored commercially useful bioactive constituents by establishing their possible pharmacological benefits.Methods: The data from published literature, confined to pharmacological manifestations of various phytocomponents of Boerhaavia diffusa L. or its parts like root, leaf and stem were extracted from scientific databases, Google, Science Direct, PubMed, etc. using its antifungal, antibacterial, anticancer, anti-inflammatory, antidiabetic, hepatoprotective, cardioprotective, renoprotective, antifertility benefits and molecular docking study as search strings and keywords. Further, the reported in silico studies for bioactivity and bioavailability are detailed.Results: The botanicals possess numerous bioactive compounds, the most widely reported ones being phenolic (punarnavoside, trans-caftaric acid, boerhavic acid), rotenoid (boeravinones A-J), flavonoid (borhaavone, quercetin, kaempferol), isoflavonoid (2′-O-methyl abronisoflavone), alkaloid (punarnavine), steroid (boerhavisterol, β-Ecdysone), anthracenes and lignans (liriodendrin, syringaresinol mono-β-D-glucoside). Some of the reported reassuring benefits of their purified forms or even the crude extracts are antidiabetic, antimicrobial, anticancer, antioxidant, anti-inflammatory, hepatoprotective, renoprotective, cardioprotective, antifertility, etc.Conclusion: The article provides an extensive study on such pharmacological utility to support the ethnomedicinal use of Boerhaavia diffusa L. and propose possible mechanism of the various bioactive compounds in optimising metabolic dysfunctions, healing and protecting vital body organs, often related to the magnificent antioxidant property of this ayurvedic panacea. Further, establishing specific roles of its yet-to-explore bioactive constituents for diverse pharmacological applications is suggested

The Crux of the Medicine Prices' Controversy in Pakistan

no abstract available

A ROUTE TO DISCOVER SMALL MOLECULE INHIBITORS OF PSAA, A POTENTIAL TARGET FOR STREPTOCOCCUS PNEUMONIAE

Due to the development of multidrug resistance in Streptococcus pneumoniae, research has begun to define new drug targets for pneumonia therapy. Different research groups have identified a lipoprotein, PsaA that is important for pneumonia virulence. PsaA is a manganese transporter that is required for bacterial virulence and growth. We have employed computer modeling to virtually screen a small-molecule database for inhibition of PsaA function by targeting the metal binding pocket, performing receptor-based virtual screening and molecular docking and scoring to identify potential inhibitors of PsaA function. We have developed an assay for screening compounds, including the use of a PsaA mutant, testing of multiple compounds, and identification of compounds that inhibit Streptococcus pneumoniae growth at concentrations less than 20 μM. We experimentally tested the effect on Mn uptake and their PsaA dependence for 42 compounds, but these experiments suggested that these compounds were affecting bacterial growth by a different mechanism

Implementing and tuning machine learning-based models for description of solubility variations of nanomedicine in supercritical solvent for development of green processing

Determination of drug solubility in supercritical solvents such as CO2 has been of great importance for preparation of nanomedicines. This study implements and tunes several machine learning models to describe the solubility of medicine and density of solvent at various pressure and temperature. The dataset used in this study consisted of the input variables, temperature, and pressure. The methods of AdaBoost algorithm to boost the performance of base regression models for predicting the mole fractions of rivaroxaban and the density of SC-CO2 were developed. The base models used include Theil-Sen Regression (TSR), Gaussian Process Regression (GPR), Automatic Relevance Determination Regression (ARD), and Linear Regression (LR). We employ the Hunter-Prey Optimization technique to tune the hyper-parameters of these models. The results indicated that the boosted models outperform their base counterparts. For the mole fraction predictions, AdaBoost with ARD achieves an R2 value of 0.95986, while AdaBoost with GPR obtains an R2 score of 0.99817. For the SC-CO2 density predictions, AdaBoost with GPR achieves an impressive R2 of 0.99906. Accordingly, the AdaBoost with GPR is the best model for both outputs. These results demonstrate AdaBoost strength and Hunter-Prey algorithm in enhancing the predictive accuracy of regression models for these chemical properties

Advanced AI modeling and optimization for determination of pharmaceutical solubility in supercritical processing for production of nanosized drug particles

This study presents a comparative analysis of three different models, namely Deep Neural Network (DNN), Quantile Regression (QR), and K-Nearest Neighbors (KNN) for the prediction of SC-CO2 density and solubility of rivaroxaban. The models were tuned using the Fireworks Algorithm (FWA) to optimize their hyperparameters. The dataset used in this analysis consisted of temperature (T), pressure (P), SC-CO2 density, and mole fractions of rivaroxaban. The results indicate that the DNN model exhibited outstanding performance in both prediction tasks. For the prediction of SC-CO2 density, the DNN model achieved an impressive R2 score of 0.99667, with a mean absolute error (MAE) of 7.61812E+00. Similarly, for the prediction of mole fractions of rivaroxaban, the DNN model achieved an excellent R2 score of 0.99831, with a very low MAE of 2.49870E-02. The KNN model also demonstrated good performance, with R2 scores of 0.9799 and 0.98029 for SC-CO2 density and mole fractions, respectively. However, it exhibited slightly higher MAE values compared to the DNN model. On the other hand, the QR model showed relatively lower accuracy in both prediction tasks, with R2 scores of 0.90873 and 0.87362 for SC-CO2 density and mole fractions, respectively. The QR model had higher MAE values, indicating larger average deviations from the true values. Overall, the DNN model outperformed both the KNN and QR models in predicting SC-CO2 density and mole fractions of rivaroxaban. These findings highlight the effectiveness of DNN models in accurately modeling and predicting complex chemical properties

USING HYDROPATHIC MOLECULAR MODELING TOOLS TO ENHANCE UNDERSTANDING OF PROTEIN-LIGAND INTERACTIONS IN BIOLOGICAL SYSTEMS

Hydropathic molecular modeling is a computer-aided molecular design technique for obtaining, representing, and understanding the properties and interactions of biomacromolecular complexes in the biological environment. Hydropathic INTeraction (HINT) is a novel empirical force field to calculate the free energy of intermolecular interaction based on experimentally determined partition coefficients (log Po/w). It includes all the expected interactions between molecules such as hydrogen bonding, hydrophobic, electrostatic, acid-base, and Coulombic interactions, entropy, solvation and others. HINT tools were used to determine, evaluate, and analyze protein-ligand interactions in different research projects: 1) We used these tools to discover small molecule inhibitors of PsaA, a potential target for Streptococcus pneumoniae. We screened and scored potential molecules to obtain hits. After the growth conditions for both the wild type and PsaA mutant of S. pneumoniae were optimized, we then tested our hits. A few compounds passed through the three-stage assay protocol and confirmed the inhibition of PsaA with MICs between 125-250 μM. 2) The SAR of C-3 and C-5 pyrrole-based antitubulin agents at the colchicine-binding site with explicitly solvated models was performed. After docking with GOLD at the colchicine site, post-docking scoring and evaluation were performed with HINT. The total HINT score correlates with binding and activity; similarly, the significance of individual functional groups, protein residues and interactions amongst a collection of compounds can be quantitated. The possibility of water-mediated interactions in a way solvent accessible part of the pocket was considered by subjecting molecular models to MD simulations. Several water molecules were identified to be contributing to the binding and were confirmed by HINT scoring. Finally, using hydropathic molecular modeling tools helped us to understand, evaluate, analyze, and improve protein-ligand interactions in different biological systems

Thermodynamic and experimental analysis of drug nanoparticles preparation using supercritical thermal processing: Solubility of Chlorothiazide in different Co-solvents

Background/purpose: Chlorothiazide is a well-known diuretic and an antihypertensive drug with poor solubility and permeability and thus low bioavailability. Producing nanoparticles of this drug via a suitable supercritical method can enhance its therapeutic efficiency. For this purpose, supercritical solubility of Chlorothiazide must be known. At 308- 338 K and 130- 290 bar, Majrashi obtained this parameter between the mole fraction of 0.417×10-5 to 1.012×10-5. The poor supercritical solubility of Chlorothiazide can be enhanced by adding a little polar co-solvent to scCO2. Model/design: In the current study, the solubility of this drug in the ternary systems of Chlorothiazide, scCO2, and different co-solvents of ethanol, DMSO, and acetone was measured. Also, the obtained experimental data were correlated by some empirical models presented by the research teams of González, Mendez-Santiago-Teja, Li, Soltani-Mazloumi, and Jouyban. Finding: The supercritical solubility of Chlorothiazide in the presence of ethanol, DMSO, and acetone was found in the mole fraction range of 1.115×10-5 to 11.895×10-5, 0.778×10-5 to 9.25×10-5, and 0.668 ×10-5 to 9.04×10-5, respectively. It has been shown that addition of these co-solvents can improve the supercritical solubility of Chlorothiazide, and in the meantime, ethanol with the greatest effect can increase it by about 2.02-11.75 times. Furthermore, the Joyban model has the most accuracy for the correlation of the obtained solubility data, and the data calculated by this model are more consistent with the experimental data. Novelty: For the first time at this work, the effect of three different co-solvents of ethanol, DMSO, and acetone on the solubility of Chlorothiazide in scCO2 was studied both experimentally and theoretically

Nanostructured lipid carriers of ivabradine hydrochloride: Optimization, characterization and in-vivo estimation for management of stable angina

Stable angina (angina pectoris) is a type of chest pain that happens when the heart muscle needs more oxygen than usual but it's not getting it at that moment because of heart disease. The drawback of the marketed formulation is required repeated administration of the drug due to low bioavailability. A recently licenced medication called ivabradine hydrochloride (IVB) is used to treat stable angina and signs of heart failure. Technical problems in the approved IBH tablets include a two-hour half-life, erratic systemic absorption, and a high rate of first-pass metabolism (>50%). We therefore created a distinctive and cutting-edge formulation of IVB using a nano formulation approach like nanostructured lipid carriers (NLCs). The response surface method with a three-level Box–Behnken design was used for the creation and improvement of IVB. The optimized formulation was proceeded for physicochemical characterizations like particle size, zeta potential, morphology (TEM and SEM), entrapment efficiency, in-vitro release, stability studies, compatibility study (DSC, FTIR and XRD), hemocompatibility study, ex-vivo permeability, and in-vivo angina study. As results, optimized formulation was found to be 114.45 ± 5.14 nm particle size with 83.45 ± 3.23% entrapment efficiency and biphasic release. The formulation showed spherical and compatible with excipients, no interaction was observed and hemocompatible. The IBH-NLCss showed more permeability (1.85 folds) as compared to the marketed dosage form. The in-vivo pharmacological activity was established in terms of decrease in severity and duration of ST-segment depression in vasopressin-induced angina model in experimental rats

Hepatoprotective and cardioprotective effect of Artemisia nilagirica leaf extract on E. coli challenged broiler chicken

Artemisia nilagirica is an important medicinal plant found to exhibit several medicinal properties but the use of its leaves for combating E. coli infection has not been scientifically validated in poultry. The present study was conducted to evaluate the protective effects of methanol leaf extract of A. nilagirica (ANE) on E. coli challenged broiler chickens. Three hundred and thirty, day-old broiler chickens, were divided into 6 groups of 55 each, with group EX infected intraperitoneally (I/P) with LD50 dose of 1 × 107 cfu/ml of E. coli; group(s) EA1, EA2 and EA3 infected I/P with 1 × 107 cfu/ml of E. coli and supplemented with ANE @ 0.5, 1.0 and 2.0 g/L of drinking water, respectively; group AX were only given ANE @ 2.0 g/L in the drinking water. ANE treatment was started from day 4 and was continuously given in the drinking water up to day 21. E. coli infection was given to the birds on day 7 of their age. The effect of the plant extract was evaluated on the basis of gross, microscopic and ultrastructural alterations in E. coli challenged broiler chickens. The extract of A. nilagirica was found to show antibacterial, cardioprotective and hepatoprotective properties in a dose-dependent manner on the basis of gross and microscopic examination. The methanol extract of A. nilagirica leaves revealed no toxic effect on the hepatocytes on ultrastructural evaluation. This study demonstrates the antimicrobial, hepatoprotective and cardioprotective activities of ANE in broiler chickens infected with E. coli organism

Antibacterial Efficacy of <i>N</i>-(4-methylpyridin-2-yl) Thiophene-2-Carboxamide Analogues against Extended-Spectrum-β-Lactamase Producing Clinical Strain of <i>Escherichia coli</i> ST 131

Development in the fields of natural-product-derived and synthetic small molecules is in stark contrast to the ongoing demand for novel antimicrobials to treat life-threatening infections caused by extended-spectrum β-lactamase producing Escherichia coli (ESBL E. coli). Therefore, there is an interest in the antibacterial activities of synthesized N-(4-methylpyridin-2-yl) thiophene-2-carboxamides (4a–h) against ESBL-producing E. coli ST131 strains. A blood sample was obtained from a suspected septicemia patient and processed in the Bactec Alert system. The isolate’s identification and antibacterial profile were determined using the VITEK 2® compact system. Multi-locus sequence typing of E. coli was conducted by identifying housekeeping genes, while ESBL phenotype detection was performed according to CLSI guidelines. Additionally, PCR was carried out to detect the blaCTX-M gene molecularly. Moreover, molecular docking studies of synthesized compounds (4a–h) demonstrated the binding pocket residues involved in the active site of the β-lactamase receptor of E. coli. The result confirmed the detection of E. coli ST131 from septicemia patients. The isolates were identified as ESBL producers carrying the blaCTX-M gene, which provided resistance against cephalosporins and beta-lactam inhibitors but sensitivity to carbapenems. Among the compounds tested, 4a and 4c exhibited high activity and demonstrated the best fit and interactions with the binding pocket of the β-lactamase enzyme. Interestingly, the maximum of the docking confirmations binds at a similar pocket region, further strengthening the importance of binding residues. Hence, the in vitro and molecular docking studies reflect the promising antibacterial effects of 4a and 4c compounds