Experimental and hypothetical appraisal on inhibition of glucose-induced glycation of bovine serum albumin by quercetin.

BACKGROUND: The specificity of protein functions depends on its folding ability into a functional structure. Protein folding is an essential systemic phenomenon that prevents incorrect folding which could result in harmful aggregation. This harmful aggregation of proteins causes neurodegenerative diseases and systemic amyloidosis. Experimental and theoretical approaches were used in this study to explicate the probable mechanisms of action of quercetin in inhibition of glucose-induced glycation through estimations of percentage glycated protein, inhibited induced protein aggregation, and unoxidized bovine serum albumin thiol groups and assessments of molecular interactions of quercetin with the structures of bovine serum albumin, amyloid beta-peptide (1-42) and 3D amyloid-beta (1-42) fibrils retrieved from the protein databank ( http://www.rcsb.org ). RESULTS: The results showed quercetin inhibited the formation of glycated protein, protein aggregation, and thiol oxidation in a concentration-dependent manner where 200 µg/ml showed the highest inhibition while 50 µg/ml depicted the least inhibition in all the studied assessments. From the docking analysis, it was observed that quercetin had a significantly higher binding affinities - 8.67 ± 0.09 kcal/mol, - 5.37 ± 0.05 kcal/mol and - 5.93 ± 0.13 kcal/mol for the bovine serum albumin, amyloid beta-peptide (1-42) and 3D amyloid-beta (1-42) fibrils respectively compared to the glucose, the inducer. Quercetin and glucose interacted with amino acid residues at the BSA subdomain IIA thus providing a clue that quercetin may impose its inhibition through the binding domain. Also, it is important to mention that the phytochemicals shared a similar interaction profile as that of glucose with the amyloid-beta. CONCLUSIONS: These findings established the beneficial effects of quercetin as a potential agent that could alleviate hyperglycaemic-initiated disorders associated with elevated serum glucose levels.

Apoptotic effects of triterpenoids isolated from Pleiocarpa pycnantha leaves in cancer cells and molecular docking study of the interactions of camptothecin and ursolic acid with human caspase 3, caspase 9 and topoisomerase I.

The aim of this study was to examine the effects of triterpenes from Pleiocarpa pycnantha leaves on the induction of apoptotic signalling in human cells. The molecular mechanisms of triterpenes isolated from P. pycnantha leaves were investigated in vitro on HeLa, MCF-7, HT-29, and KMST-6 cells. The compounds activated several markers associated with apoptosis, viz., phosphatidylserine translocation, caspase activation, oxidative stress, and topoisomerase I inhibition. Compounds 1 and 5 were non-selective, whereas compounds 2, 3, and 4 showed potential as cancer-specific agents by selectively inducing apoptosis only on cancer cells. Theoretical studies on the interactions of compound 1 with caspases -3 and -9 and topoisomerase I were carried out through a molecular docking study and illustrated that compound 1 had an equal binding affinity with the caspases and topoisomerase I comparable to that of camptothecin. The cellular pathway activated by these compounds was dependent on the compound and the cell type.

Glycation Inhibition of Bovine Serum Albumin by Extracts of Momordica charantia L. using Spectroscopic and Computational Methods.

Background: Momordica charantia (M. charantia) has been used in traditional medicine for the management of complications associated with diabetes mellitus. Several phytochemicals with different pharmacological properties have been previously identified from the botanical; however, the mechanisms of actions of this plant vis-à-vis inhibition of non-enzymatic protein glycation are not known. This study aimed at understanding the putative mechanisms underlying the antiglycation properties of M. charantia extracts experimental and theoretical approaches. Methods: The antiglycation properties of the plant were evaluated by studying the inhibitory actions of methanol and aqueous extracts on glucose-induced glycation of Bovine Serum Albumin (BSA) and protein aggregation. The mode of binding of identified phenolics of the botanical with BSA, amyloid beta-peptide (1-42) and 3D amyloid beta (1-42) fibrils were also investigated. Results: The in vitro experimental properties of the extracts showed that the extracts could prevent inductions of protein glycation and protein folding. The molecular docking analyses revealed that phenolics had better binding affinities with chlorogenic acid showing the highest binding score (-7.13±0.04 kcal/mol) towards BSA than glucose and their respective interactions with BSA could prevent glucose-induced protein aggregation. Conclusion: Consequently, the results of this study provide insight into the probable mechanisms of actions of the extracts of M. charantia against the inhibition of advanced glycation end products formation.

Modulation of mitochondrial permeability transition pore opening by Myricetin and prediction of its-drug-like potential using in silico approach.

Myricetin has been demonstrated to have multiple biological functions with promising research and development prospects. This study investigated the effect of myricetin on liver mitochondrial membrane permeability transition pores and its inhibitory potential on proteins that are important in the apoptotic process in silico. Mitochondrial swelling was assessed as changes in absorbance under succinate-energized conditions. Cytochrome c release, mitochondrial-lipid peroxidation, caspase 3 and 9 expressions, as well as calcium ATPase, were assessed. Pharmacokinetic properties of myricetin were predicted through the SwissADME server while the binding affinity of myricetin toward the proteins was computed using the AutodockVina Screening tool. The conformational stability of protein-ligand interactions was evaluated using molecular dynamics simulations analysis through the iMODS server. Myricetin inhibited the opening of the mitochondrial permeability transition pore and also reversed the increase in mitochondrial lipid peroxidation caused by calcium and other toxicants. Myricetin also caused a reduction in the expression of caspase 3 and 9 as well as calcium ATPase activity. The molecular docking results revealed that myricetin had a considerable binding affinity to the pocket site of caspase 3 and 9 as well as calcium ATPase. Myricetin showed a good drug-likeness based on the predicted pharmacokinetic properties as revealed by low CYP 450 inhibitory promiscuity and relatively low toxicity. It could therefore be suggested that myricetin could be useful in the management of diseases where too many apoptosis occur characterized by excessive tissue wastage such as neurodegenerative conditions and could as well play a role in protecting the physicochemical properties of membrane bilayers from free radical-induced severe cellular damage.

Pharmacoinformatics and hypothetical studies on allicin, curcumin, and gingerol as potential candidates against COVID-19-associated proteases.

Medicinal plants have been known to provide the essential raw material for the majority of antiviral drugs. This study demonstrated the putative inhibitory potential of curcumin, allicin, and gingerol towards cathepsin K, COVID-19 main protease, and SARS-CoV 3 C-like protease. The pharmacokinetic properties were predicted through the SwissADME server while the corresponding binding affinity of the selected phytocompounds towards the proteins was computed using PyRx-Python Prescription 0.8 and the binding free energy were computed based on conventional molecular dynamics using LARMD server. The ADMET properties revealed all the drugs possess drug-like properties. Curcumin has the highest binding affinities with all the selected proteases while allicin has the lowest binding affinities towards the proteases. Moreover, it was observed that curcumin exhibited the highest binding free energy of -17.90 ± 0.23,  -18.21 ± 0.25, and -9.67 ± 0.08 kcal/mol for Cathepsin K, COVID-19 main protease, and SARS-CoV 3 C-like protease, respectively. Based on the activities of the phytocompounds against coronavirus target proteases involved in the viral entry as evident from the results, the study, therefore, suggests that these phytocompounds could be valuable for the development of drugs useful for the prevention of coronavirus entry and replication.Communicated by Ramaswamy H. Sarma.

Molecular Mechanisms of Anti-Inflammatory Activities of the Extracts of Ocimum gratissimum and Thymus vulgaris.

BACKGROUND: A large body of literature suggests that the extracts of Ocimum gratissimum (O. gratissimum) and Thymus vulgaris (T. vulgaris) play protective roles against various inflammatory disorders. However, the possible mechanism of action with reference to the interactions of their respective phytochemical compositions with pro-inflammatory mediators as the indication of their therapeutic effects is less clear. Therefore, the immunomodulatory properties of O. gratissimum and T. vulgaris were investigated in this study. METHODS: The in vitro lipoxygenase inhibitory potentials of methanolic extracts of the selected plants were assessed through colorimetric analysis. The pharmacokinetics of some identified compounds in the botanicals were investigated via the Swiss ADME server while the molecular interactions of the compounds with lipoxygenase, IL-1, IL-6, TNF-α, IL-8, and CCL-2 were performed through molecular docking. RESULTS: The assessment of the lipoxygenase inhibition revealed the extracts could possess anti-inflammatory agents. The pharmacokinetic results of some selected compounds identified in the botanicals showed moderate toxic effects compared to indomethacin. The molecular docking study substantiated the report of the in vitro analysis as indicated in the binding score of all the selected compounds compared to indomethacin. CONCLUSION: The phytochemical components of the extracts of O. gratissimum and T. vulgaris could be effective as anti-inflammatory agents that could be explored in preventing disorders associated with excessive activities of pro-inflammatory mediators.

Repositioning of Fungal-based Peptides as Modulators of Angiotensin-converting Enzyme-related Carboxypeptidase, SARS-coronavirus HR2 Domain, and Coronavirus Disease 2019 Main Protease.

BACKGROUND AND OBJECTIVES: Angiotensin-converting enzyme-related carboxypeptidase, SARS-Coronavirus HR2 Domain, and COVID-19 main protease are essential for the cellular entry and replication of coronavirus in the host. This study investigated the putative inhibitory action of peptides form medicinal mushrooms, namely Pseudoplectania nigrella, Russula paludosa, and Clitocybe sinopica, towards selected proteins through computational studies. MATERIALS AND METHODS: The respective physicochemical properties of selected peptides were predicted using ProtParam tool, while the binding modes and binding free energy of selected peptides toward proteins were computed through HawkDock server. The structural flexibility and stability of docked protein-peptide complexes were assessed through iMODS server. RESULTS: The peptides showed an optimum binding afinity with the molecular targets; plectasin from P. nigrella showed the highest binding free energy compared to peptides from R. paludosa and C. sinopica. Besides, molecular dynamic simulations showed all fungal-based peptides could influence the flexibility and stability of selected proteins. CONCLUSION: The study revealed fungal-based peptides could be explored as functional modulators of essential proteins that are involved in the cellular entry of coronavirus.

Repurposing of chloroquine and some clinically approved antiviral drugs as effective therapeutics to prevent cellular entry and replication of coronavirus.

The reemergence of coronavirus prompts the need for the development of effective therapeutics to prevent the cellular entry and replication of coronavirus. This study demonstrated the putative inhibitory potential of lopinavir, remdesivir, oseltamir, azithromycin, ribavirin, and chloroquine towards V-ATPase, protein kinase A, SARS-CoV spike glycoprotein/ACE-2 complex and viral proteases. The pharmacodynamic and pharmacokinetic properties were predicted through the pkCSM server while the corresponding binding affinity of the selected drugs towards the proteins was computed using AutodockVina Screening tool. The ADMET properties revealed all the drugs possess drug-like properties. Lopinavir has the highest binding affinities to the pocket site of SARS-CoV spike glycoprotein/ACE-2 complex, cyclic AMP-dependent protein kinase A and 3-Chymotrypsin like protease while redemsivir has the highest binding affinities for vacuolar proton-translocating ATPase (V-ATPase) and papain-like proteins. The amino acids Asp269, Leu370, His374, and His345 were predicted as the key residues for lopinavir binding to human SARS-CoV spike glycoprotein/ACE-2 complex while His378, Tyr515, Leu73, Leu100, Phe32 and Phe40 for remdesivir and Tyr510, Phe504, Met62, Tyr50, and His378 were predicted for azithromycin as the key residues for binding to SARS-CoV spike glycoprotein/ACE-2 complex. Moreover, it was also observed that chloroquine has appreciable binding affinities for 3-Chymotrpsin- like protease and cyclic AMP-dependent protein kinase A when compared to Oseltamivir and ribavirin. The study provided evidence suggesting putative repurposing of the selected drugs for the development of valuable drugs for the prevention of cellular entry and replication of coronavirus.Communicated by Ramaswamy H. Sarma.

Fatty acid compositions of ether extracts of Bryophyllumpinnatum Lam., Ficus exasperata Vahl., Gossypium herbaceum Linn. and Hilleria latifolia (Lam.) H. Walt / Composición de ácidos grasos de extractos etéreos de Bryophyllum pinnatum Lam., Ficus exasperata Vahl., Gossypium herbaceum Linn. y Hilleria latifolia (Lam.) H. Walt

SUMMARY Currently, there is a growing interest in identifying alternative sources of fatty acids due to the present increasing demand for oil-rich botanicals in industrial applications. The main objective of this work was to identify the fatty acid compositions of ether extracts of dried leaves of Bryophyllum pinnatum Lam., Ficus exasperata Vahl., Gossypium herbaceum Linn. and Hilleria latifolia (Lam.) H. Walt. The fatty acids were analyzed by gas chromatography with flame ionization detector. Among the evaluated ether extracts, the higher contents of saturated fatty acids were found in H. latifolia (27.96%) with the principal presence of stearic acid compared to the content of the saturated fatty acids in B. pinnatum (0.53%), F. exasperata (0.04%) and G. herbaceum (0.47%). Equally, the result showed that H. latifolia contained the highest percentage of unsaturated fatty acids with the predominant presence of oleic acid with the amount of 41.04%. Linoleic acid was also found to have the highest value in H. latifolia with the amount of 20.41%. Stearic acid, oleic acid, and linoleic acid were found in all the samples. The extract of H. latifolia contained a healthy mixture of different types of fatty acids thus suggesting it as a probable source of suitable fatty acids.

RESUMEN Actualmente, existe un creciente interés en identificar fuentes alternativas de ácidos grasos debido a la creciente demanda actual de productos botánicos ricos en aceite en aplicaciones industriales. El objetivo principal de este trabajo fue identificar las composiciones de ácidos grasos de extractos de éter de hojas secas de Bryophyllum pinnatum Lam., Ficus exasperata Vahl., Gossypium herbaceum Linn. y Hilleria latifolia (Lam.) H. Walt. Los ácidos grasos fueron analizados por cromatografía de gases con detector de ionización de llama. Entre los extractos de éter evaluados, los mayores contenidos de ácidos grasos saturados se encontraron en H. latifolia (27,96%) con presencia principal de ácido esteárico en comparación con el contenido de los ácidos grasos saturados en B. pinnatum (0,53%), F. exasperata (0,04%) y G. herbaceum (0,47%). Igualmente, el resultado mostró que la H. latifolia contenía el mayor porcentaje de ácidos grasos insaturados con presencia predominante de ácido oleico con una cantidad de 41,04%. También se encontró que el ácido linoleico tiene el valor más alto en H. latifolia con una cantidad de 20,41%. Se encontró ácido esteárico, ácido oleico y ácido linoleico en todas las muestras. El extracto de H. latifolia contenía una mezcla saludable de diferentes tipos de ácidos grasos, lo que sugiere que es una fuente probable de ácidos grasos adecuados.