In vivo and in silico study of allicin as a stroke prevention

Abstract

Aim: To prove allicin effect to prevent stroke in insilico and invivo method. Introduction: Stroke is a disease that can cause permanent disability, even death. Atherosclerosis is one of the cause of stroke. One way to prevent stroke is to treat atherosclerosis using allicin. Allicin works by inhibiting Integrin Alpha Beta-3 and ApoE proteins. Therefore, allicin can be considered as an alternative in stroke prevention. Methods: This is true experimental study with two methods. Allicin was taken from pubchem, while ApoE with code (1EA8), Integrin Alpha Beta-3 with code (1JX5) taken from protein data bank. Afterwards, the ligands and macromolecule were docked with Pyrx. Analysis was done using Discovery Studio. Pharmacokinetic study, allicin compounds were analyzed with ACD/I-Lab. During invivo study, rats were induced with high fat diet for 8 weeks and were given allicin with dose 5, 10, 20mg/kg BW during 6 weeks. Rat blood, carotid artery, and brain were analyzed for lipid profile, foam cells in blood vessels, and immunohistochemically to see BDNF. Results: Pharmacokinetic results showed that allicin has oral bioavailability above 70%, distributed through lipoproteins and a few albumins. Allicin can penetrate through membrane and cytoplasm, affecting its target. Pharmacodynamically, allicin can bind to active site of ApoE on 149 leucine, and to active side of ApoE on 173 serine. Allicin bound with active site of ApoE will increase ApoE expression, thus lowering lipid profile except HDL. Meanwhile, allicin bound with active site of Integrin Alpha Beta-3 blocked platelet aggregation. Decreasing Integrin Alpha Beta-3 was proven by invivo results where foam cells were decreasing. These events caused a decrease foam cell in common artery, causing no brain hypoxia and increased BDNF. Invivo test showed a decrease in foam cells on 10mg/kg BW. On the contrary, the brain showed an increase in BDNF amount on 20mg/kg BW. Conclusion: Based on insilico and invivo studies, allicin can be considered as a preventive treatment to stroke by inhibiting atherosclerosis development by increasing ApoE, lowering Integrin Alpha Beta-3 protein, and increasing BDNF.1–5