Some significant compounds present in annatto are geranylgeraniol and tocotrienols. These compounds have beneficial effects against hyperlipidemia and chronic diseases, where oxidative stress and inflammation are present, but the exact mechanism of action of such activities is still a subject of research. This study aimed to evaluate possible mechanisms of action that could be underlying the activities of these molecules. For this, in silico approaches such as ligand topology (PASS and SEA servers) and molecular docking with the software GOLD were used. Additionally, we screened some pharmacokinetic and toxicological parameters using the servers PreADMET, SwissADME, and ProTox-II. The results corroborate the antidyslipidemia and anti-inflammatory activities of geranylgeraniol and tocotrienols. Notably, some new mechanisms of action were predicted to be potentially underlying the activities of these compounds, including inhibition of squalene monooxygenase, lanosterol synthase, and phospholipase A₂. These results give new insight into new mechanisms of action involved in these molecules from annatto and Chronic^®.

Dyslipidemia is a metabolic condition linked to increased morbidity. This study aimed to evaluate the effect of two new nutraceuticals derived from annatto (Bixa orellana), açaí (Euterpe oleracea), and soybean germ or red clover isoflavones (Trifolium pratense) against high-fat-induced dyslipidemia in female Wistar rats. The formulations were assessed through GC-MS and HPLC-UV/Vis. Next, female Wistar rats received daily administrations of coconut oil and were treated with Ormona^® SI (OSI), Ormona^® RC (ORC), soybean germ (SG), simvastatin (simv.), simvastatin + Ormona^® SI (simv. + OSI), or only distilled water (control). Biochemical tests were performed using the animals’ blood, and their arteries were screened for atheroma formation. The results show abnormal TC, TG, LDL, and HDL levels caused by the high-fat diet, increased glucose levels, hepatotoxicity, nephrotoxicity, and atherogenesis. The nutraceuticals significantly ameliorated all conditions, with results that are similar to the group treated with simvastatin. Notably, the groups treated with either Ormona^® or simvastatin + Ormona^® had better liver protection than those treated only with SG or simvastatin; additionally, the nutraceuticals could prevent atherogenesis, unlike SG. The results indicate a high efficacy of the nutraceuticals in preventing dyslipidemia and its complications.