4.2 Article

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

Journal

DRUG AND CHEMICAL TOXICOLOGY
Volume 46, Issue 5, Pages 1004-1014

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/01480545.2022.2117372

Keywords

Myricetin; permeability transition pore; apoptosis; pharmacokinetics; molecular docking

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This study explored the effects of myricetin on liver mitochondria and its potential as an inhibitor for proteins involved in apoptosis. The results showed that myricetin inhibited the opening of mitochondrial pores and reversed lipid peroxidation caused by calcium. It also reduced the expression of caspase 3 and 9 and affected calcium ATPase activity. Molecular docking revealed strong binding affinity between myricetin and the target proteins. The study suggests that myricetin may be useful in managing diseases characterized by excessive apoptosis and in protecting cell membranes from severe damage.
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.

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