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. 2022 Feb 4;15(2):198.
doi: 10.3390/ph15020198.

7-Acetoxyhorminone from Salvia multicaulis Vahl. as Promising Inhibitor of 3-Hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) Reductase

Serkan Yigitkan  1   2 , Abdulselam Ertas  3   4 , Ramin Ekhteiari Salmas  5 , Mehmet Firat  6 , Ilkay Erdogan Orhan  2
Affiliations

7-Acetoxyhorminone from Salvia multicaulis Vahl. as Promising Inhibitor of 3-Hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) Reductase

Serkan Yigitkan et al. Pharmaceuticals (Basel). .

Abstract

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 Salvia multicaulis 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%, IC50 = 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.

Keywords: HMG-CoA reductase; Salvia; enzyme inhibition; hypercholesterolemia; terpenoids.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical formulae of the isolated compounds: 6,7-dehydroyleanone (1), 12-demethylmulticaulin (2), ferruginol (3), 12-hydroxy abieta-1, 3, 5(10), 8, 11, 13-hexaene (4), β-sitosterol (e5), horminone (6), 7-acetoxyhorminone (7), pisiferal (8), ursolic acid (9), and oleanolic acid (10).
Figure 2
Figure 2
Two-dimensional ligand diagrams of horminone–7-acetoxyhorminone (left) and 7-acetoxyhorminone (right). The chemical properties of the amino acids are represented by different colors.
Figure 3
Figure 3
Distribution of the binding energies of horminone–7-acetoxyhorminone (1) and 7-acetoxyhorminone (2).
Figure 4
Figure 4
Chemical formulae of the isolated compounds, i.e., 7-acetoxyhorminone (1) and atorvastatin (2).
See this image and copyright information in PMC

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