Triticum aestivum Octacosanol, a Potential Inhibitor of PCSK9 in Fat Diet–Induced Hypercholesteromia

Proprotein convertase subtilisin-like kexin type 9 (PCSK9) is a circulating serine protease that promotes the degradation of low-density lipoprotein receptors, and its elevated levels are associated with hypercholesterolemia and cardiovascular disease. Wheatgrass (Triticum aestivum L., Poaceae) juice is widely consumed by health enthusiasts due to its potential health benefits, including positive effects on lipid profiles. Octacosanol has been shown to possess anti-inflammatory and antioxidant properties, and previous studies have suggested that it may have a role in regulating lipid metabolism. This study aimed to investigate the effects of octacosanol, a bioactive component derived from wheatgrass, on serum levels of proprotein convertase subtilisin-like kexin type 9 (PCSK9) and lipid profiles. The study used a ligand binding prediction approach to identify potential binding sites on PCSK9 for octacosanol. A total of 20 sites were predicted, and stable docking of octacosanol in the catalytic domain of PCSK9 was mediated through hydrogen bonds and hydrophobic interactions with surrounding 15 residues. The best docked conformation of octacosanol-PCSK9 exhibited a binding energy of − 11.31 kcal/mol, inhibition constant of 5.09 nM, and intermolecular energy of − 11.61 kcal/mol. The results of the study showed that octacosanol was able to significantly reduce both serum and hepatic levels of PCSK9. These findings suggest that octacosanol may be a potential therapeutic agent for the regulation of PCSK9 and lipid metabolism.