7-Acetoxyhorminone from <i>Salvia multicaulis</i> Vahl. as Promising Inhibitor of 3-Hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) Reductase
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....
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MDPI AG
2022-02-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/2/198 |
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| author | Serkan Yigitkan Abdulselam Ertas Ramin Ekhteiari Salmas Mehmet Firat Ilkay Erdogan Orhan |
| author_facet | Serkan Yigitkan Abdulselam Ertas Ramin Ekhteiari Salmas Mehmet Firat Ilkay Erdogan Orhan |
| author_sort | Serkan Yigitkan |
| collection | DOAJ |
| description | 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 <i>Salvia multicaulis</i> 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<sub>50</sub> = 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. |
| first_indexed | 2024-03-09T21:15:43Z |
| format | Article |
| id | doaj.art-31d6512afb5b45c1aee0cdc102edc8ff |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T21:15:43Z |
| publishDate | 2022-02-01 |
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| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-31d6512afb5b45c1aee0cdc102edc8ff2023-11-23T21:34:35ZengMDPI AGPharmaceuticals1424-82472022-02-0115219810.3390/ph150201987-Acetoxyhorminone from <i>Salvia multicaulis</i> Vahl. as Promising Inhibitor of 3-Hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) ReductaseSerkan Yigitkan0Abdulselam Ertas1Ramin Ekhteiari Salmas2Mehmet Firat3Ilkay Erdogan Orhan4Department of Pharmaceutical Botany, Faculty of Pharmacy, Dicle University, 21200 Diyarbakir, TurkeyDepartment of Analytical Chemistry, Faculty of Pharmacy, Dicle University, 21200 Diyarbakir, TurkeyDepartment of Chemistry, Britannia House, King’s College, London SE1 1DB, UKDepartment of Biology, Faculty of Education, Van Yuzuncu Yil University, 65080 Van, TurkeyDepartment of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330 Ankara, Turkey3-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 <i>Salvia multicaulis</i> 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<sub>50</sub> = 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.https://www.mdpi.com/1424-8247/15/2/198hypercholesterolemiaHMG-CoA reductaseenzyme inhibition<i>Salvia</i>terpenoids |
| spellingShingle | Serkan Yigitkan Abdulselam Ertas Ramin Ekhteiari Salmas Mehmet Firat Ilkay Erdogan Orhan 7-Acetoxyhorminone from <i>Salvia multicaulis</i> Vahl. as Promising Inhibitor of 3-Hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) Reductase Pharmaceuticals hypercholesterolemia HMG-CoA reductase enzyme inhibition <i>Salvia</i> terpenoids |
| title | 7-Acetoxyhorminone from <i>Salvia multicaulis</i> Vahl. as Promising Inhibitor of 3-Hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) Reductase |
| title_full | 7-Acetoxyhorminone from <i>Salvia multicaulis</i> Vahl. as Promising Inhibitor of 3-Hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) Reductase |
| title_fullStr | 7-Acetoxyhorminone from <i>Salvia multicaulis</i> Vahl. as Promising Inhibitor of 3-Hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) Reductase |
| title_full_unstemmed | 7-Acetoxyhorminone from <i>Salvia multicaulis</i> Vahl. as Promising Inhibitor of 3-Hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) Reductase |
| title_short | 7-Acetoxyhorminone from <i>Salvia multicaulis</i> Vahl. as Promising Inhibitor of 3-Hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) Reductase |
| title_sort | 7 acetoxyhorminone from i salvia multicaulis i vahl as promising inhibitor of 3 hydroxy 3 methylglutaryl coenzyme a hmg coa reductase |
| topic | hypercholesterolemia HMG-CoA reductase enzyme inhibition <i>Salvia</i> terpenoids |
| url | https://www.mdpi.com/1424-8247/15/2/198 |
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