The Exploration of 6-Gingerol and 6-Shogaol using Network Pharmacology and Molecular Docking as Potential Inhibitors of Atherogenesis
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Abstract
Atherosclerosis is the narrowing of blood vessels due to fatty plaque buildup in the intimal layer. Preventing atherosclerosis is a promising treatment avenue. Research shows that ginger (Zingiber officinale), particularly its active compounds 6-gingerol and 6-shogaol, can lower total cholesterol and LDL (low-density lipoprotein) levels, although the mechanisms remain unclear. The Comparative Toxigenomics Database was used to identify genes interacting with 6-gingerol and 6-shogaol, followed by enrichment analysis via ShinyGO and mapping onto KEGG pathways to identify upstream protein regulators. Docking studies were conducted using AutoDock 4.2, with visualization in Discovery Studio. Five proteins emerged as potential targets: PPAR-γ (peroxisome proliferator-activated receptor gamma), PPAR-δ (peroxisome proliferator-activated receptor delta), LOX-1 (lectin-like oxidized low-density lipoprotein receptor 1), ACAT1 (acetyl-CoA acetyltransferase 1), and PI3K (phosphoinositide 3-kinase gamma). 6-gingerol and 6-shogaol inhibited PI3K, PPAR-δ, and LOX-1 similarly to their co-crystallized ligands. However, the docking protocols could not account for LOX-1 tetramerization or ACAT1 steric hindrance, highlighting the need for further investigation into these interactions. Regarding PPAR-γ, the compounds did not show compatible interaction patterns, making it an unlikely target. The experiment provides insight into how 6-gingerol and 6-shogaol may affect lipid metabolism and atherosclerosis, mainly interacting with PI3K, PPAR-δ, and LOX-1. No supporting evidence was found for their interaction with the other tested proteins.
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