Ja'far UMAR, TURHADI, Eko SUYANTO, Titin Andri WIHASTUTI, FATCHIYAH
Journal of Research in Pharmacy - 2025;29(6):2486-2507
Obesity -related hypercholesterolemia, a significant risk factor for cardiovascular disease, is metabolic disorder characterized by elevated fatty acid and cholesterol biosynthesis. Brown rice ( Oryza sativa L.), a functional food with diverse pharmacological properties, is believed to possess potent anti -obesity and anti -cholesterol effects. This study aimed to identify a potent compound from brown rice that could inhibit key enzymes involved in lipid biosynthesis: fatty acid synthase (FASN), 3 -hydroxy -3-methylglutaryl -CoA synthase 1 (HMGCS1), and 3 -hydroxy -3-methylglutaryl -CoA reductase (HMGCR). To achieve this, bioactive compounds from brown rice were screened for drug -likeness, toxicity, and bioactivity. M olecular docking was performed to evaluate the binding affinities of selected compounds to the target proteins and was continued molecular dynamic simulation . Among the twenty -six compounds analyzed, five were identified as promising candidates for anti -obesity and anti -cholesterol activities. Trans -3-hydroxycinnamic acid emerged as the most potent compound, exhibiting strong binding affinities to the active sites of FASN (Leu2222, Phe2423), HMGCS1 (Cys129, Tyr171, Ser377), and HMGCR (Glu559, Gly806, Thr809 , Met655). Importantly, this compound formed stronger and closer interactions with FASN ( -7.4 kcal/mol) and HMGCS1 ( -7.2 kcal/mol) compared to the respective drug controls (orlistat and hymeglusin). However, its binding affinity to HMGCR (-6.2 kcal/mol) was weaker than that of simvastatin ( -8.3 kcal/mol). Notably, molecular dynamic result s demonstrated that the interaction trans -3-hydroxycinnamic acid with FASN and HMGC R was stable . By effectively inhibiting FASN and HMGC R1, trans -3-hydroxycinnamic acid fro m brown rice has the potential to regulate lipid metabolism, suppress obesity, and prevent complications associated with hypercholesterolemia.
