Role of Alkannin in the Therapeutic Targeting of Protein-Tyrosine Phosphatase 1B and Aldose Reductase in Type 2 Diabetes: An In Silico and In Vitro Evaluation.

Alkannin is a plant-derived naphthoquinone that is isolated from the Boraginaceae family plants. In our previous studies, we found that shikonin, which is the R-enantiomer of alkannin, has potent antidiabetic activity by inhibiting the action of the aldose reductase (AR) enzyme and the protein-tyrosine phosphatase 1B (PTP1B). Therefore, in this study, we aim to explore the antidiabetic effect of alkannin targeting PTP1B and AR by employing in silico and in vitro techniques. For in silico, we used different parameters such as ADMET analysis, molecular docking, MD simulation, Root Mean Square Deviation (RMSD), protein-ligand mapping, and free binding energy calculation. The in vitro evaluation was done by assessing the inhibitory activity and enzyme kinetics of PTP1B and AR inhibition by alkannin. The in silico studies indicate that alkannin possesses favorable pharmacological properties and possesses strong binding affinity for diabetes target proteins. Hydrogen bonds (Val297, Ala299, Leu300, and Ser302) and hydrophobic interactions (Trp20, Val47, Tyr48, Trp79, Trp111, Phe122, Trp219, Val297, Cys298, Ala299, Leu300, and Leu301) are established by the compound, which potentially improves specificity and aids in the stabilization of the protein-ligand complex. The results from in vitro studies show a potent dose-dependent PTP1B inhibitory activity with an IC50 value of 19.47 µM, and toward AR it was estimated at 22.77 µM. Thus, from the results it is concluded that a low IC50 value of alkannin for both PTP1B and AR along with favorable pharmacological properties and optimal intra-molecular interactions indicates its utilization as a potential drug candidate for the management of diabetes and its end complications.

Harnessing medicinal plant compounds for the control of Campylobacter in foods: a comprehensive review.

Campylobacter is a major foodborne and zoonotic pathogen, causing severe human infections and imposing a substantial economic burden on global public health. The ongoing spread and emergence of multidrug-resistant (MDR) strains across various fields exacerbate therapeutic challenges, raising the incidence of diseases and fatalities. Medicinal plants, renowned for their abundance in secondary metabolites, exhibit proven efficacy in inhibiting various foodborne and zoonotic pathogens, presenting sustainable alternatives to ensure food safety. This review aims to synthesize recent insights from peer-reviewed journals on the epidemiology and antimicrobial resistance of Campylobacter species, elucidate the in vitro antibacterial activity of medicinal plant compounds against Campylobacter by delineating underlying mechanisms, and explore the application of these compounds in controlling Campylobacter in food. Additionally, we discuss recent advancements and future prospects of employing medicinal plant compounds in food products to mitigate foodborne pathogens, particularly Campylobacter. In conclusion, we argue that medicinal plant compounds can be used as effective and sustainable sources for developing new antimicrobial alternatives to counteract the dissemination of MDR Campylobacter strains.

Spices as Sustainable Food Preservatives: A Comprehensive Review of Their Antimicrobial Potential.

Throughout history, spices have been employed for their pharmaceutical attributes and as a culinary enhancement. The food industry widely employs artificial preservatives to retard the deterioration induced by microbial proliferation, enzymatic processes, and oxidative reactions. Nevertheless, the utilization of these synthetic preservatives in food products has given rise to significant apprehension among consumers, primarily stemming from the potential health risks that they pose. These risks encompass a spectrum of adverse effects, including but not limited to gastrointestinal disorders, the disruption of gut microbiota, allergic reactions, respiratory complications, and concerns regarding their carcinogenic properties. Consequently, consumers are displaying an increasing reluctance to purchase preserved food items that contain such additives. Spices, known for their antimicrobial value, are investigated for their potential as food preservatives. The review assesses 25 spice types for their inherent antimicrobial properties and their applicability in inhibiting various foodborne microorganisms and suggests further future investigations regarding their use as possible natural food preservatives that could offer safer, more sustainable methods for extending shelf life. Future research should delve deeper into the use of natural antimicrobials, such as spices, to not only replace synthetic preservatives but also optimize their application in food safety and shelf-life extension. Moreover, there is a need for continuous innovation in encapsulation technologies for antimicrobial agents. Developing cost-effective and efficient methods, along with scaling up production processes, will be crucial to competing with traditional antimicrobial options in terms of both efficacy and affordability.

Synthesis and Photophysical, Electrochemical, and DFT Studies of Piperidyl and Pyrrolidinyl Chalcones.

Small organic molecules with interesting optical and electrochemical properties find applications as organic luminescent materials. In this work, we report the synthesis of novel chalcones with D-A-D and D-A-D-A architecture, followed by their optical, electrochemical, and computational studies. The absorption band of these compounds occurs at 360-480 nm with emission maxima appearing around 513-552 nm. The large Stokes shifts (Δλ) for all compounds (90-132 nm) suggest intramolecular charge transfer (ICT) in the excited states. The molar absorptivity and fluorescence quantum yields were found to be in the range of 1.7-4.26 × 104 M-1 cm-1 and 0.29-0.39, respectively. The electrochemical parameters were determined by using cyclic voltammetry (CV). Density functional theory (DFT) calculations of all compounds were made by using B3LYP/G (d,p) functionals in chloroform and were found to have a good correlation with experimental results. Preliminary studies of absorption, photoluminescence, CV, and their theoretical correlation suggest that these compounds may be optimized for their applications in optoelectronics, sensing, and bioimaging.

Unveiling Chemical, Antioxidant and Antibacterial Properties of Fagonia indica Grown in the Hail Mountains, Saudi Arabia.

The Aja and Salma mountains in the Hail region are home to a variety of indigenous wild plants, some of which are used in Bedouin folk medicine to treat various ailments. The purpose of the current study was to unveil the chemical, antioxidant and antibacterial properties of Fagonia indica (Showeka) grown widely in these mountains, as data on the biological activities of this plant in this remote area are scarce. XRF spectrometry indicated the presence of some essential elements, which were in the order of Ca > S > K > AL > CL > Si > P > Fe > Mg > Na > Ti > Sr > Zn > Mn. Qualitative chemical screening revealed the presence of saponins, terpenes, flavonoids, tannins, phenols and cardiac glycosides in the methanolic extract (80% v/v). GC-MS showed the presence of 2-chloropropanoic acid 18.5%, tetrahydro-2-methylfuran 20.1%, tridecanoic acid 12-methyl-, methyl ester 2.2%, hexadecanoic acid, methyl ester 8.6%, methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl) propionate 13.4%, methyl linoleate 7.0%, petroselinic acid methyl ester 15%, erucylamide 6.7% and diosgenin 8.5%. Total phenols, total tannins, flavonoids, DPPH, reducing power, -carotene and ABTS IC50 (mg/mL) scavenging activity were used to measure the antioxidant capabilities of Fagonia indica, which exhibited prominent antioxidant properties at low concentrations when compared to ascorbic acid, butylate hydroxytoluene and beta-carotene. The antibacterial investigation revealed significant inhibitory effects against Bacillus subtilis MTCC121 and Pseudomona aeruginosa MTCC 741 with inhibition zones of 15.00 ± 1.5 and 12.0 ± 1.0 mm, respectively. The MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) ranged between 125 to 500 µg/mL. The MBC/MIC ratio indicated possible bactericidal efficacy against Bacillus subtilis and bacteriostatic activity against Pseudomona aeruginosa. The study also showed that this plant has anti-biofilm formation activity.

Computational analysis of PTP-1B site-directed mutations and their structural binding to potential inhibitors.

Protein tyrosine phosphatase-1B (PTP-1B) is a well-known therapeutic target for diabetes and obesity as it suppresses insulin and leptin signaling. PTP-1B deletion or pharmacological suppression boosted glucose homeostasis and insulin signaling without altering hepatic fat storage. Inhibitors of PTP-1B may be useful in the treatment of type 2 diabetes, and shikonin, a naturally occurring naphthoquinone dye pigment, is reported to inhibit PTP-1B and possess antidiabetic properties. Since the cell contains a large number of phosphatases, PTP-1B inhibitors must be effective and selective. To explore more about the mechanism underlying the inhibitor's efficacy and selectivity, we investigated its top four pharmacophores and used site-directed mutagenesis to insert amino acid mutations into PTP-1B as an extension of our previous study where we identified 4 pharmacophores of shikonin. The study aimed to examine the site-directed mutations like R24Y, S215E, and S216C influence the binding of shikonin pharmacophores, which act as selective inhibitors of PTP-1B. To achieve this purpose, docking and molecular dynamics simulations of wild-type (WT) and mutant PTP-1B with antidiabetic compounds were undertaken. The simulation results revealed that site-directed mutations can change the hydrogen bond and hydrophobic interactions between shikonin pharmacophores and many residues in PTP-1B's active site, influencing the drug's binding affinity. These findings could aid researchers in better understanding PTP-1B inhibitors' selective binding mechanism and pave the path for the creation of effective PTP-1B inhibitors.

Identification of Putative Plant-Based ALR-2 Inhibitors to Treat Diabetic Peripheral Neuropathy.

Diabetic peripheral neuropathy (DPN) is a common diabetes complication (DM). Aldose reductase -2 (ALR-2) is an oxidoreductase enzyme that is most extensively studied therapeutic target for diabetes-related complications that can be inhibited by epalrestat, which has severe adverse effects; hence the discovery of potent natural inhibitors is desired. In response, a pharmacophore model based on the properties of eplarestat was generated. The specified pharmacophore model searched the NuBBEDB database of natural compounds for prospective lead candidates. To assess the drug-likeness and ADMET profile of the compounds, a series of in silico filtering procedures were applied. The compounds were then put through molecular docking and interaction analysis. In comparison to the reference drug, four compounds showed increased binding affinity and demonstrated critical residue interactions with greater stability and specificity. As a result, we have identified four potent inhibitors: ZINC000002895847, ZINC000002566593, ZINC000012447255, and ZINC000065074786, that could be used as pharmacological niches to develop novel ALR-2 inhibitors.

Antiviral Efficacy of Selected Natural Phytochemicals against SARS-CoV-2 Spike Glycoprotein Using Structure-Based Drug Designing.

SARS-CoV-2 is a highly virulent coronavirus that first surfaced in late 2019 and has since created a pandemic of the acute respiratory sickness known as "coronavirus disease 2019" (COVID-19), posing a threat to human health and public safety. S-RBD is a coronaviral protein that is essential for a coronavirus (CoV) to bind and penetrate into host cells. As a result, it has become a popular pharmacological target. The goal of this study was to find potential candidates for anti-coronavirus disease 2019 (COVID-19) drugs by targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S-RBD with novel bioactive compounds and molecular interaction studies of 15,000 phytochemicals belonging to different flavonoid subgroups. A spike protein crystal structure attached to the ACE2 structure was obtained from the PDB database. A library of 15,000 phytochemicals was made by collecting compounds from different databases, such as the Zinc-database, PubChem-database, and MPD3-database. This library was docked against a receptor binding domain of a spike glycoprotein through the Molecular Operating Environment (MOE). The top drug candidates Phylloflavan, Milk thistle, Ilexin B and Isosilybin B, after virtual screening, were selected on the basis of the least binding score. Phylloflavan ranked as the top compound because of its least binding affinity score of -14.09 kcal/mol. In silico studies showed that all those compounds showed good activity and could be used as an immunological response with no bioavailability issues. Absorption, distribution, metabolism, excretion and a toxicological analysis were conducted through SwissADME. Stability and effectiveness of the docked complexes were elucidated by performing the 100 ns molecular dynamic simulation through the Desmond package.

Iridium-Catalyzed C-H Borylation of CF3-Substituted Pyridines.

Iridium-catalyzed C-H borylation of CF3-substituted pyridines is described in this paper. The boronic ester group can be installed on the α, ß, or γ position of pyridine by an appropriate substitution pattern. Sterically governed regioselectivity provides convenient access to a variety of CF3-substituted pyridylboronic esters. These catalytic C-H borylation reactions were carried out neatly without the use of any solvent. Several functional groups, such as halo, ester, alkoxy, amino, etc., are compatible with this methodology. These pyridylboronic esters are amenable to column chromatography and the products were isolated in good to excellent yields. α-Borylated pyridines, although isolated in good yields, do not have a long shelf life. The boronic ester derivatives of these CF3-substituted pyridines can serve as useful precursors in the synthesis regime.

Assessment of The Antibacterial Susceptibility of Ocimum basilicum.

       The current study was designed to assess the antibacterial activities of an ethanol extract of Ocimum basilicum (O. basilicum). Using disc diffusion and direct contact methods, the extracts were tested in vitro against three bacterial strains. The direct contact test was used and compared with the agar diffusion test. The optical density was measured using a spectrophotometer to collect data. The results showed that methanol extracts of plant parts of O. basilcum leaves contained tannins, flavonoids, glycosides, and steroids, whereas alkaloids, saponins, and terpenoids. In contrast, O. basilcum seeds contained saponins, flavonoids, and steroids. The O. basilicum stems contained saponins and flavonoids, O. basilucum had antibacterial activity against the identified bacteria. The plant extracts inhibited Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli (E. coli). The result revealed that the Ocimum basilicum leaves were more potent than seeds and stems. Ocimum basilicum ethanol extract combined with established conventional antibiotics may enhance their antimicrobial properties, giving rise to synergistic effects against clinically important bacterial species.

Identification of Causative agents associated with decay of Trees Twig and Orchards Die-back and their Impacts on Vessels of Citrus, Date Palm and Ficus.

The present work is concerned with the studies of the organism causing wood decay of twigs and branches of citrus orchards, date palm Phoenix dactylifera L, and ficus trees. A survey for the occurrence of this disease in the main growing areas was achieved by the researchers. The following species of citrus orchards [lime (C. aurantifolia), sweet orange (C. sinensis), and mandarin (C. reticulate)] were surveyed, and so date palm and ficus trees. However, the results showed that the incidence of this disease was about 100%. Laboratory examinations data revealed mainly two fungal species causing the disease: Physalospora rhodina (P.rhodina)  and Diaporthe citri (D. citri). In addition that, both fungi, which are P. rhodina and D. citri affected the vessels of tree tissues. According to the pathogenicity test, the fungus P. rhodina caused a breakdown of parenchyma cells, and the fungus D. citri caused the darkening of the xylem.

In silico characterization, docking, and simulations to understand host-pathogen interactions in an effort to enhance crop production in date palms.

Food safety remains a significant challenge despite the growth and development in agricultural research and the advent of modern biotechnological and agricultural tools. Though the agriculturist struggles to aid the growing population's needs, many pathogen-based plant diseases by their direct impact on cell division and tissue development have led to the loss of tons of food crops every year. Though there are many conventional and traditional methods to overcome this issue, the amount and time spend are huge. Scientists have developed systems biology tools to study the root cause of the problem and rectify it. Host-pathogen protein interactions (HPIs) have a promising role in identifying the pathogens' strategy to conquer the host organism. In this paper, the interactions between the host Rhynchophorus ferrugineus (an invasive wood-boring pest that destroys palm) and the pathogens Proteus mirabilis, Serratia marcescens, and Klebsiella pneumoniae are comprehensively studied using protein-protein interactions, molecular docking, and followed by 200 ns molecular dynamic simulations. This study elucidates the structural and functional basis of these proteins leading towards better plant health, production, and reliability.

Nutritional value of Kejeik: a dry fish product of the Sudan.

Kejeik product samples were collected from two different locations in Sudan including Singah city (Blue Nile) and Kusti city (White Nile). The contents of protein, moisture, ash, fat, crude fiber and carbohydrates varied considerably and ranged between 63.52-78.06, 5.37-6.69, 5.78-11.8, 9.04-16.13, 0.55-1.34 and 0.59-1.61% respectively, in the various Kejeik samples. However, the production area has a non-significant effect in most of the chemical components. All Kejeik samples contained appreciable amounts of macro-minerals and the calcium was the highest in all samples. In addition, Kejeik samples contained most of the micro-minerals, however, Nawk and Ijl Kejeik collected from Singah contained the lowest concentrations of iron. The study concluded that Kejeik is a safe food with a highly nutritive value which is recommended to be utilized in Sudanese meals especially during shortage of protein and other nutrients sources.