Molecular Docking of Flindersine with some targets related to β-cells Protection

Diabetes mellitus (DM) is the most widespread metabolic disorder affecting millions worldwide. Molecular docking studies are useful in identifying some useful ligands which could be used to target proteins related to β-cell protection.  Flindersine isolated from the plant Toddalia asiatica (L.) Lam. (Rutaceae) has been shown by us to possess antidiabetic property. With a view to identify in silico the possible mode of docking with different target proteins like PPARγ and GLUT4 which play important roles in protecting β-cells from damage. Chemical characteristics of Flindersine were retrieved from pubchem database http://pubchem.ncbi.nlm.nih.gov. The docking analysis in the active sites of 2PRG and Homology modeled protein structure of GLUT4 were performed by the Auto dock program. The docking results showed good binding interactions of the ligand with both the targets at very low energy level. In our in silico analysis, flindersine isolated from Toddalia asiatica clearly demonstrated that it could improve  diabetic condition by increasing insulin secretion from remnant or regenerated pancreatic beta cells and could promote insulin sensitization and glucose uptake activities. When compared with standard drug Rosiglitazone that is commercially available flindersine can further diminish the degree of shrinkage and necrosis of beta cells of pancreas. Thus flindersine can be considered for developing into a potent antidiabetic drug

Proyecto de factibilidad para la implementación de una máquina dispensadora de jugos “Deliejuice

The objective of this entrepreneurship project was to determine the feasibility for the implementation of a natural juice dispensing machine in the Latacunga canton, the feasibility project was carried out based on the problem that there are too many drinks processed with various alternate chemicals in current drinks. such as juices, sodas and moisturizers, that is why a study is carried out to implement a natural juice machine where the fruit is the main component for the juice, since these have great benefits such as vitamins, minerals and natural proteins that allow care consumer health.El presente proyecto de emprendimiento tuvo como objetivo determinar la factibilidad para la implementación de una máquina dispensadora de jugos naturales en el cantón Latacunga, el proyecto de factibilidad se lo realizo basándose en el problema que existe demasiadas bebidas procesadas con varios químicos alternos en las bebidas actuales como jugos, gaseosas e hidratantes, es por ello que se realiza un estudio para implementar una máquina de jugos naturales donde la fruta sea el principal componente para el jugo, al contar estas con grandes beneficios como vitaminas, minerales y proteínas naturales que permiten el cuidado de salud de los consumidores

Diseño y construcción de una máquina para la aplicación de pintura efecto cromo en la empresa Maquilu ubicada en la ciudad de Ambato.

A machine design and building was objective of this project for the application of chrome effect paint on metal and plastic surface parts, supporting the company Maquilu needs, which chose to implement the chemical chrome plating method that provides a metallic and mirror-like appearance manually, due to the economic factor. However, the main drawback that arose in the company when implementing this method is the time, used to perform the process, which leads to low chromed parts production. For this work development, a qualitative and quantitative methodology was used, which helped to have a machine design and building complete vision. Regarding its building and operation, the machine uses a rotating plate that supports a maximum load of 25 kg and rotates at an optimum working speed of 24.7 rpm determined by an experimental analysis; obtaining this speed in the machine, a system of pulleys and belts connected to an electric motor of 1540 rpm was implemented; to carry out the application process, a pneumatic distribution system was used to meet the needs of the machine. To carry out the experimental tests, a piece with an area of 0.055 m2 was taken into consideration, and by means of the proportions table, the exact quantities of the chemical compounds for the proposed area were determined. The spray guns were calibrated at 2.5 bars in order to avoid over application and waste of the chemical compounds. In addition, the machine allowed the operator to perform the process in half the time compared to the previous method, which means an increase in the final production parts with good results.El presente proyecto tiene como objetivo el diseño y la construcción de una máquina para la aplicación de pintura efecto cromo en piezas de superficies metálicas y plásticas, para solventar la necesidad de la empresa Maquilu que optó por implementar el método del cromado químico que brinda una apariencia metálica y de tipo espejo de forma manual, debido al factor económico. Sin embargo, el principal inconveniente que se presentó en la empresa al implementar este método, es el tiempo empleado para realizar el proceso, lo que conlleva a la baja producción de piezas cromadas. Para el desarrollo de este trabajo se utilizó una metodología cualitativa y cuantitativa, que ayudó a tener una visión completa del diseño y la construcción de la máquina. En cuanto a su construcción y funcionamiento la máquina emplea un plato giratorio que soporta una carga máxima de 25 kg y gira a una velocidad óptima de trabajo de 24,7 rpm determinado mediante un análisis experimental; para obtener esta velocidad en la máquina se le implementó un sistema de poleas y bandas conectadas a un motor eléctrico de 1540 rpm; para realizar el proceso de aplicación se empleó un sistema de distribución neumático que solventa las necesidades de la máquina. Para realizar las pruebas experimentales se tomó en consideración una pieza con un área de 0,055 m 2, y mediante la tabla de proporciones se determinó las cantidades exactas de los compuestos químicos para el área planteada, las pistolas pulverizadoras se calibró a 2,5 bares con la finalidad de evitar la sobre aplicación y el desperdicio de los compuestos químicos. Además, la máquina permitió al operario realizar el proceso en la mitad del tiempo en comparación al método anterior, lo que significa un aumento en la producción de piezas finales con buenos resultados

Synthesis of a 1,2,3-bistriazole derivative of embelin and evaluation of its effect on high-fat diet fed-streptozotocin-induced type 2 diabetes in rats and molecular docking studies

The embelin derivative 2a was synthesized with the 1,2,3-bistriazole and spectral data confirmed its structural identity. Anti-diabetic and anti-lipidemic effects were evaluated using HFD-STZ induced type 2 diabetic rats. The derivative 2a (30 mg/kg b wt.) supplementation significantly (PPeer reviewe

Topical antifungal keratitis therapeutic potential of Clitoria ternatea Linn. flower extract: phytochemical profiling, in silico modelling, and in vitro biological activity assessment

IntroductionFungal keratitis (FK) poses a severe threat to vision, potentially leading to blindness if not promptly addressed. Clitoria ternatea flower extracts have a history of use in Ayurvedic and Indian traditional medicines, particularly for treating eye ailments. This study investigates the antifungal and antibiofilm effects of Clitoria ternatea flower extracts on the FK clinical isolate Coniochaeta hoffmannii. Structural details and key compound identification were analysed through FTIR and GC-MS.MethodsThe minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of Clitoria ternatea flower extracts were determined using broth dilution and well plate techniques. Biofilm inhibitory activity was assessed through microscopic evaluation, while anti-irritant and cytotoxic properties were evaluated using CAE-EI and MTT assays. Through GC-MS and FT-IR analysis the compounds dissolved in the extract and their functional group were studied, and their toxicity screening and pharmacokinetic prediction were conducted in silico. Subsequently, compounds with high corneal permeability were further identified, and molecular docking and simulation studies at 150 ns were used to investigate their interactions with fungal virulence factors and human inflammatory proteins.Results and DiscussionAt a concentration of 250 µg/mL, the Clitoria ternatea flower extract displayed effective biofilm inhibition. MIC and MFC values were determined as 500 and 1000 µg/mL, respectively. CAE-EI and MTT assays indicated no significant irritant and cytotoxic effects up to a concentration of 3 mg/mL. Compounds like 9,9-dimethoxybicyclo[3.3.1]nonane-2,4-dione showed high corneal permeability with strong and stable interactions with fungal virulence cellobiose dehydrogenase, endo β 1,4 xylanase, and glucanase, as well as corneal inflammation-associated human TNF-α and Interleukin IL-1b protein targets. The findings indicate that extracts from C. ternatea flowers could be formulated for an effective and safe alternative for developing new topical FK therapeutics

Corrigendum: Revealing the mechanism of Huazhi Rougan granule in the treatment of nonalcoholic fatty liver through intestinal flora based on 16S rRNA, metagenomic sequencing and network pharmacology

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Geranii Herba as a Potential Inhibitor of SARS-CoV-2 Main 3CLpro, Spike RBD, and Regulation of Unfolded Protein Response: An In Silico Approach

Background: Since the first patient identified with SARS-CoV-2 symptoms in December 2019, the trend of a spreading coronavirus disease 2019 (COVID-19) infection has remained to date. As for now, there is an urgent need to develop novel drugs or vaccines for the SARS-CoV-2 virus. Methods: Polyphenolic compounds have potential as drug candidates for various diseases, including viral infections. In this study, polyphenolic compounds contained in Geranii Herba were chosen for an in silico approach. The SARS-CoV-2 receptor-binding domain (RBD), 3CLpro (Replicase polyprotein 1ab), and the cell surface receptor glucose-regulated protein 78 (GRP78) were chosen as target proteins. Results: Based on the molecular docking analysis, ellagic acid, gallic acid, geraniin, kaempferitrin, kaempferol, and quercetin showed significant binding interactions with the target proteins. Besides, the molecular dynamic simulation studies support Geranii Herba’s inhibition efficiency on the SARS-CoV-2 RBD. We assume that the active compounds in Geranii Herba might inhibit SARS-CoV-2 cell entry through the ACE2 receptor and inhibit the proteolytic process. Besides, these compounds may help to regulate the cell signaling under the unfolded protein response in endoplasmic reticulum stress through the binding with GRP78 and avoid the SARS-CoV-2 interaction. Conclusions: Hence, the compounds present in Geranii Herba could be used as possible drug candidates for the prevention/treatment of SARS-CoV-2 infection

Inhibitory Effects of 2-Aminoethoxydiphenyl Borate (2-APB) on Three K_V1 Channel Currents

2-Aminoethoxydiphenyl borate (2-APB), a boron-containing compound, is a multitarget compound with potential as a drug precursor and exerts various effects in systems of the human body. Ion channels are among the reported targets of 2-APB. The effects of 2-APB on voltage-gated potassium channels (KV) have been reported, but the types of KV channels that 2-APB inhibits and the inhibitory mechanism remain unknown. In this paper, we discovered that 2-APB acted as an inhibitor of three representative human KV1 channels. 2-APB significantly blocked A-type Kv channel KV1.4 in a concentration-dependent manner, with an IC50 of 67.3 μM, while it inhibited the delayed outward rectifier channels KV1.2 and KV1.3, with IC50s of 310.4 μM and 454.9 μM, respectively. Further studies on KV1.4 showed that V549, T551, A553, and L554 at the cavity region and N-terminal played significant roles in 2-APB’s effects on the KV1.4 channel. The results also indicated the importance of fast inactivation gating in determining the different effects of 2-APB on three channels. Interestingly, a current facilitation phenomenon by a short prepulse after 2-APB application was discovered for the first time. The docked modeling revealed that 2-APB could form hydrogen bonds with different sites in the cavity region of three channels, and the inhibition constants showed a similar trend to the experimental results. These findings revealed new molecular targets of 2-APB and demonstrated that 2-APB’s effects on KV1 channels might be part of the reason for the diverse bioactivities of 2-APB in the human body and in animal models of human disease

Protective effects of Ficus carica leaves on glucose and lipids levels, carbohydrate metabolism enzymes and β-cells in type 2 diabetic rats

Context: The decoctions of Ficus carica Linn. (Moraceae) leaves are used in the folklore treatment of diabetes. Objective: To evaluate the effect of F. carica on glucose and lipids levels, carbohydrate metabolism enzymes and β-cells protective effects in type 2 diabetes. Material and methods: Diabetes was induced in 15 days high-fat diet (HFD)-fed Wistar rats by intraperitoneal injection of streptozotocin (STZ) (40 mg/kg). The ethyl acetate extract (250 and 500 mg/kg) of F. carica leaves was administered for 28 days. Oral glucose tolerance (OGTT) and intraperitoneal insulin tolerance tests (ITT) were evaluated on 15th and 25th days, respectively. Results: The ethyl acetate extract (250 and 500 mg/kg) of n F. carica leaves showed significant effect (p < 0.005) in the levels of blood glucose, total cholesterol (TC), triglycerides (TG), body weight and hepatic glycogen. In OGTT, F. carica (250 and 500 mg/kg) significantly (p < 0.005) detained the increase in blood glucose levels at 60 and 120 min and in ITT, F. carica enhanced the glucose utilization significantly (p < 0.005) over 30 and 60 min compared to diabetic control. Further, the altered activities of key carbohydrate metabolizing enzymes such as glucose-6-phosphatase, fructose-1,6-bisphosphatase and hexokinase in the liver tissue of diabetic rats were significantly (p < 0.005) reverted to near normal levels upon treatment with F. carica. Immumohistochemical studies of islets substantiated the cytoprotective effect on pancreatic β-cells. Discussion and conclusions: F. carica leaves exerted significant effect on carbohydrate metabolism enzymes with promising hypoglycemic and hypolipidemic activities in type 2 diabetic rats