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

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 ICµ <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. [ABSTRACT FROM AUTHOR]