Potential of the Compounds from Bixa orellana Purified Annatto Oil and Its Granules (Chronic®) against Dyslipidemia and Inflammatory Diseases: In Silico Studies with Geranylgeraniol and Tocotrienols

Abstract

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®.

The Biomedical Importance of the Missing Pathway for Farnesol and Geranylgeraniol Salvage

“…Statins, used to manage dyslipidemias, also possess several side effects, including headache, dizziness, discomfort or weakness in skeletal muscles, constipation, diarrhea, and hepatotoxicity [118]. Specifically, hepatotoxicity and muscle pain are the most severe side effects, and are associated with deficiencies in protein prenylation [94,119,120]. Furthermore, long term treatment with statins has been shown to decrease dolichol and ubiquinone levels and, as a consequence, makes organisms more susceptible to oxidative damage, and to be inefficient in protein post-translational modifications and in obtaining energy via oxidative phosphorylation [94,119,120].…”

“…Specifically, hepatotoxicity and muscle pain are the most severe side effects, and are associated with deficiencies in protein prenylation [94,119,120]. Furthermore, long term treatment with statins has been shown to decrease dolichol and ubiquinone levels and, as a consequence, makes organisms more susceptible to oxidative damage, and to be inefficient in protein post-translational modifications and in obtaining energy via oxidative phosphorylation [94,119,120]. Despite statin side effects being rarely severe, at times it is necessary to stop the therapy, exposing the patient to an increased cardiac risk [118].…”

“…However, these complements were not demonstrated to satisfactorily reduce those major side effects, and ubiquinone was poorly orally absorbed [121,122]. Recently, commercial GGOH rich extracts and preparations were launched that have shown promising effects of restoring protein prenylation in this context [94,119,120]. In particular, GGOH supplements supported a beneficial effect against statin-induced myopathy and in the prevention of skeletal muscle fatigue in preliminary studies [119,120].…”

Plantas medicinais utilizadas no tratamento de dislipidemias: uma revisão integrativa

“…Na redução de CT especificamente, a Bixa orellana L. obteve melhor desempenho. Esta redução também foi constatada por Batista et al (2022). Esta é estudada para tratamentos de saúde como inflamações e dislipidemias graças aos benefícios que podem estar relacionados à presença de tocotrienol e geranilgeraniol na composição desta planta (Batista et al, 2022).…”

“…Esta redução também foi constatada por Batista et al (2022). Esta é estudada para tratamentos de saúde como inflamações e dislipidemias graças aos benefícios que podem estar relacionados à presença de tocotrienol e geranilgeraniol na composição desta planta (Batista et al, 2022). Isto se dá através da regulação negativa da redutase HMG-CoA (HGMR) que causa redução na taxa de biossíntese de colesterol e triglicerídeos.…”