New Insights into Polyphenols in Plants as Potential Modulators of Atherosclerosis by Acting on Lipoprotein Lipase: In Silico Molecular Docking and In Vitro Studies

Epidemiological studies have shown that polyphenols that are widely distributed in vegetables and fruits reduce the risk of cardiovascular diseases, which are caused by altered lipoprotein metabolism. Lipoprotein lipase (LPL) plays a pivotal role in lipoprotein metabolism. Although the antioxidant and anti-inflammatory activities of polyphenols are known, little is known about the effects of polyphenols on lipoprotein metabolism via LPL activity. Therefore, the aim of this study was to determine the effects of polyphenols on LPL activity using in silico molecular docking and in vitro studies. The polyphenols investigated here included quercetin, rutin, and apigenin. When measured by in silico molecular docking, some polyphenols, such as quercetin, rutin, and naringin, provided a low docking energy, suggesting that they may inhibit the LPL activity by interacting with Ser159 and His268, the catalytic residues of LPL. An in vitro study subsequently showed that the investigated polyphenols tended to have lower LPL activities, and their inhibitory activities were greater than that of orlistat, a commercially available inhibitor of LPL. Additionally, the degree of inhibition in vitro was positively and significantly related to the binding energy of polyphenols in silico. The structure–inhibitory activity relationship also suggested the possibility that the structure of the B ring, rather than the A and C rings, may be more important in regulating LPL activity. In conclusion, in addition to its antioxidant and anti-inflammatory activities, because LPL is involved in the uptake of lipids into arteries from the systemic circulation, we propose that polyphenols may in part diminish the risk of cardiovascular disease by inhibiting LPL activity in arteries.