Drug design targeting the AMPK signalling pathway with herbal medicines for atherosclerosis therapy

Abstract Background: Atherosclerosis (AS) is a vascular disease which causes cardiovascular diseases such as stroke, heart attack and acute coronary syndrome. It is a major cause of death worldwide, especially in developed countries. In AS, the artery walls become thickened due to the accumulation and invasion of white blood cells (foam cells) and form a fibro-fatty plaque. Hence, these investigations aim to identify the potential applications of herbal compounds targeting the AMPK signalling pathway for AS therapy. Methods: In this investigation, in vitro kinase activity was determined for a set of herbal compounds present in herbal plants and herbal medicines against 5′ AMP-activated protein kinase (AMPK). This enzyme plays a vital role in AS, having an effect on the invasion and accumulation of white blood cells, leading to the thickening of artery walls and vascular remodelling. In addition, a molecular docking simulation study was carried out for the AMPK enzyme (PDB ID: 3AQV) against the herbal compounds. Results: The in vitro kinase activity showed that 10 of the herbal compounds possessed IC50 values lower than 10 μM, which showed the potent inhibitory effect of the AMPK enzyme. In addition, a molecular docking simulation carried out on the AMPK enzyme (PDB ID: 3AQV) against the herbal compounds observed a positive correlation with IC50 values and docking scores of the docked compounds with an IC50 <10 μM. The subsequent protein-ligand interaction analyses for the best docking hits showed favourable interactions. Also, the molecular dynamics simulation enabled the generation of a trajectory file for the RMSD backbone, illustrating the stability of the docked protein-ligand complex without any structural fluctuations. Conclusions: The study concludes that baicalin, curcumin, campesterol, emodin and gingerol provide a promising lead for AS and can therefore be prescribed for the treatment of AS.