Yigitkan Serkan, Ertas Abdulselam, Salmas Ramin Ekhteiari, Firat Mehmet, Orhan Ilkay Erdogan
Department of Pharmaceutical Botany, Faculty of Pharmacy, Dicle University, 21200 Diyarbakir, Turkey.
Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330 Ankara, Turkey.
Pharmaceuticals (Basel). 2022 Feb 4;15(2):198. doi: 10.3390/ph15020198.
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is a key enzyme involved in cholesterol biosynthesis and one of the most important targets for the treatment of hypercholesterolemia. A limited number of studies on the HMG-CoA reductase inhibitory potential of natural products are available. Thus, in the current study, we aimed to test the HMG-CoA reductase inhibitory capacity of extracts from the roots and aerial parts of Vahl., through activity-guided isolation. Our findings revealed that the root extract prepared with dichloromethane-acetone (1:1) showed the highest inhibition (71.97 ± 0.37%) at 100 µg/mL. The extract was then initially fractionated by column chromatography and the obtained fractions were monitored by thin layer chromatography. Fractions which were similar to each other were combined and a total of 15 fractions were obtained. Further conventional chromatographic studies were carried out on the active fractions. Based on these fractions, 10 known compounds, comprising 9 terpenes and 1 steroid derivative in total, were isolated and their structures were verified by a combination of IT-TOF-MS, and 1D and 2D NMR techniques. According to the enzyme inhibition data of the identified compounds, 7-acetoxyhorminone exerted the highest inhibition (84.15 ± 0.10%, IC = 63.6 ± 1.21 µg/mL). The molecular docking experiments on 7-acetoxyhorminone and horminone indicated that both compounds strongly bind to the active site of the enzyme.
3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶是参与胆固醇生物合成的关键酶，也是治疗高胆固醇血症最重要的靶点之一。关于天然产物对HMG-CoA还原酶抑制潜力的研究数量有限。因此，在本研究中，我们旨在通过活性导向分离来测试来自Vahl.根和地上部分提取物的HMG-CoA还原酶抑制能力。我们的研究结果表明，用二氯甲烷 - 丙酮（1:1）制备的根提取物在100μg/mL时表现出最高的抑制率（71.97±0.37%）。然后通过柱色谱对该提取物进行初步分离，所得馏分通过薄层色谱进行监测。将彼此相似的馏分合并，共得到15个馏分。对活性馏分进行了进一步的常规色谱研究。基于这些馏分，总共分离出10种已知化合物，包括9种萜类化合物和1种甾体衍生物，并通过IT-TOF-MS以及一维和二维核磁共振技术相结合的方法对其结构进行了验证。根据所鉴定化合物的酶抑制数据，7-乙酰氧基霍尔米酮表现出最高的抑制率（84.15±0.10%，IC = 63.6±1.21μg/mL）。对7-乙酰氧基霍尔米酮和霍尔米酮的分子对接实验表明，这两种化合物都能强烈结合到该酶的活性位点。
