Molecular rationale delineating the role of lycopene as a potent HMG-CoA reductase inhibitor: in vitro and in silico study

This study initially aimed to depict the molecular rationale evolving the role of lycopene in inhibiting the enzymatic activity of β-hydroxy-β-methylglutaryl-CoA (HMG-CoA) reductase via in vitro and in silico analysis. Our results illustrated that lycopene exhibited strong HMG-CoA reductase inhibitory activity (IC₅₀ value of 36 ng/ml) quite better than pravastatin (IC₅₀ = 42 ng/ml) and strong DPPH free radical scavenging activity (IC₅₀ value = 4.57 ± 0.23 μg/ml) as compared to ascorbic acid (IC₅₀ value = 9.82 ± 0.42 μg/ml). Moreover, the K_i value of lycopene (36 ng/ml) depicted via Dixon plot was well concurred with an IC₅₀ value of 36 ± 1.8 ng/ml. Moreover, molecular informatics study showed that lycopene exhibited binding energy of −5.62 kcal/mol indicating high affinity for HMG-CoA reductase than HMG-CoA (ΔG: −5.34 kcal/mol). Thus, in silico data clearly demonstrate and support the in vitro results that lycopene competitively inhibit HMG-CoA reductase activity by binding at the hydrophobic portion of HMG-CoA reductase.