Department of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, Ondo State, Nigeria.
Department of Biochemistry, Federal University of Agriculture, Abeokuta, Nigeria.
J Pharm Pharmacol. 2021 Sep 7;73(10):1377-1386. doi: 10.1093/jpp/rgab103.
Inhibition of HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, the rate rate-determining enzyme for the biogenesis of cholesterol is known to show antineoplastic effects. Therefore, this study investigates the in-silico HMG-CoA reductase (HMGCR)-inhibitory and in-vivo anti-lipidaemic/anticancer effects of carotenoids from Spondias mombin.
Carotenoids from S. mombin leaves were characterized with the aid of liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). The characterized phytochemicals were obtained from PubChem. They were docked into the orthosteric site of human HMGCR (Protein Data Bank code 1HW8) using AutoDock 4.0 suites. DMBA (7,12-dimethylbenz[a]anthracene) model of breast cancer was treated with the carotenoids extract from S. mombin (100 mg/kg and 200 mg/kg doses) to assess its anti-lipidaemic cum anticancer effects.
Carotenoids from S. mombin; beta-carotene-15,15'-epoxide, astaxanthin and 7,7',8,8'-tetrahydro-β-β-carotene demonstrate HMGCR inhibition. They form hydrophobic interactions with key residues within the catalytic domain of HMGCR. The carotenoids extract exhibits anti-lipidaemic/anticancer effects, lowering serum triglyceride, LDL and cholesterol concentration. It increases HDL concentration and downregulates the expression of HMGR, AFP, CEACAM-3, BRCA-1 and HIF-1 mRNAs.
Carotenoids from S. mombin demonstrate HMG-CoA reductase (HMGCR) inhibition, anti-lipidaemic, and anticancer effects. The inhibition of HMGCR by the carotenoids extract further poses it as a potential anti-hypercholesterolaemia compounds.
抑制 HMG-CoA（3-羟基-3-甲基戊二酰辅酶 A）还原酶，该酶是胆固醇生物合成的限速酶，已知具有抗肿瘤作用。因此，本研究探讨了 Spondias mombin 叶中的 HMG-CoA 还原酶（HMGCR）的计算机抑制作用和体内抗脂血症/抗癌作用。
利用液相色谱-电喷雾电离质谱（LC-ESI-MS）对 S. mombin 叶中的类胡萝卜素进行了表征。从 PubChem 获得了特征化的植物化学物质。使用 AutoDock 4.0 套件将它们对接到人 HMGCR 的正位（蛋白数据库代码 1HW8）。用 S. mombin （100mg/kg 和 200mg/kg 剂量）的类胡萝卜素提取物处理 DMBA（7,12-二甲基苯并[a]蒽）乳腺癌模型，以评估其抗脂血症和抗癌作用。
S. mombin 的类胡萝卜素；β-胡萝卜素-15,15'-环氧化物、虾青素和 7,7',8,8'-四氢-β-β-胡萝卜素表现出 HMGCR 抑制作用。它们与 HMGCR 催化结构域内的关键残基形成疏水相互作用。类胡萝卜素提取物具有抗脂血症/抗癌作用，降低血清甘油三酯、LDL 和胆固醇浓度。它增加了高密度脂蛋白的浓度，并下调了 HMGR、AFP、CEACAM-3、BRCA-1 和 HIF-1 mRNA 的表达。
S. mombin 的类胡萝卜素显示出 HMG-CoA 还原酶（HMGCR）抑制、抗脂血症和抗癌作用。类胡萝卜素提取物对 HMGCR 的抑制作用进一步使其成为一种潜在的抗高胆固醇血症化合物。
