Alvi Sahir Sultan, Iqbal Danish, Ahmad Saheem, Khan M Salman
a Clinical Biochemistry & Natural Product Research Laboratory, Department of Biosciences , Integral University , Lucknow , India.
Nat Prod Res. 2016 Sep;30(18):2111-4. doi: 10.1080/14786419.2015.1108977. Epub 2015 Nov 7.
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 Ki 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.
本研究最初旨在通过体外和计算机模拟分析，阐述番茄红素在抑制β-羟基-β-甲基戊二酰辅酶A（HMG-CoA）还原酶活性中所起作用的分子原理。我们的结果表明，番茄红素表现出很强的HMG-CoA还原酶抑制活性（IC50值为36 ng/ml），比普伐他汀（IC50 = 42 ng/ml）更好，并且与抗坏血酸（IC50值 = 9.82±0.42 μg/ml）相比，具有很强的DPPH自由基清除活性（IC50值 = 4.57±0.23 μg/ml）。此外，通过狄克逊图得出的番茄红素的Ki值（36 ng/ml）与IC50值36±1.8 ng/ml高度一致。此外，分子信息学研究表明，番茄红素的结合能为-5.62 kcal/mol，表明其对HMG-CoA还原酶的亲和力高于HMG-CoA（ΔG：-5.34 kcal/mol）。因此，计算机模拟数据清楚地证明并支持了体外实验结果，即番茄红素通过结合在HMG-CoA还原酶的疏水部分来竞争性抑制HMG-CoA还原酶活性。
