{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T09:43:37Z","timestamp":1780047817805,"version":"3.53.1"},"reference-count":56,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T00:00:00Z","timestamp":1643932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003356","name":"Gazi University","doi-asserted-by":"publisher","award":["02\/2018-16"],"award-info":[{"award-number":["02\/2018-16"]}],"id":[{"id":"10.13039\/501100003356","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>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\u2013acetone (1:1) showed the highest inhibition (71.97 \u00b1 0.37%) at 100 \u00b5g\/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 \u00b1 0.10%, IC50 = 63.6 \u00b1 1.21 \u00b5g\/mL). The molecular docking experiments on 7-acetoxyhorminone and horminone indicated that both compounds strongly bind to the active site of the enzyme.<\/jats:p>","DOI":"10.3390\/ph15020198","type":"journal-article","created":{"date-parts":[[2022,2,6]],"date-time":"2022-02-06T20:38:40Z","timestamp":1644179920000},"page":"198","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["7-Acetoxyhorminone from Salvia multicaulis Vahl. as Promising Inhibitor of 3-Hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) Reductase"],"prefix":"10.3390","volume":"15","author":[{"given":"Serkan","family":"Yigitkan","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Botany, Faculty of Pharmacy, Dicle University, 21200 Diyarbakir, Turkey"},{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2193-8386","authenticated-orcid":false,"given":"Abdulselam","family":"Ertas","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Pharmacy, Dicle University, 21200 Diyarbakir, Turkey"},{"name":"Cancer Research Center, Dicle University, 21200 Diyarbakir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3888-5070","authenticated-orcid":false,"given":"Ramin Ekhteiari","family":"Salmas","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Britannia House, King\u2019s College, London SE1 1DB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Firat","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Education, Van Yuzuncu Yil University, 65080 Van, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7379-5436","authenticated-orcid":false,"given":"Ilkay Erdogan","family":"Orhan","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, 06330 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"705","DOI":"10.3923\/ijp.2010.705.711","article-title":"Inhibitory activity of some plant methanol extracts on 3-hydroxy-3-methylglutaryl coenzyme a reductase","volume":"6","author":"Gholamhoseinian","year":"2010","journal-title":"Int. J. Pharmacol."},{"key":"ref_2","first-page":"10","article-title":"A mini-review on hyperlipidemia: Common clinical problem","volume":"4","author":"Singh","year":"2018","journal-title":"J. Interv. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"20963","DOI":"10.1074\/jbc.272.34.20963","article-title":"Low density lipoprotein oxidation and its pathobiological significance","volume":"272","author":"Steinberg","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"509","DOI":"10.2147\/DDDT.S75056","article-title":"HMG-CoA reductase inhibitory activity and phytocomponent investigation of Basella alba leaf extract as a treatment for hypercholesterolemia","volume":"9","author":"Baskaran","year":"2015","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.2174\/1570180816666181112144353","article-title":"The natural products as hydroxymethylglutaryl-CoA reductase inhibitors","volume":"16","author":"Orhan","year":"2019","journal-title":"Lett. Drug Des. Discov."},{"key":"ref_6","unstructured":"Yigitkan, S. (2020). Investigation of Some Plants Grown in Turkey for Their HMG (3-hydroxy-3-methyl-glutaryl) CoA Reductase Inhibitory Effect (Supervisor: Prof.Dr. Ilkay Erdogan Orhan). [Ph.D. Thesis, Gazi University]."},{"key":"ref_7","first-page":"413","article-title":"Inhibitory effects on the HMG-CoA Reductase in the chemical constituents of the Cassia mimosoides Linn","volume":"24","author":"Shen","year":"2016","journal-title":"Rev. Romana Medicina Lab."},{"key":"ref_8","first-page":"13","article-title":"Essential oil composition of the aerial parts of two Salvia L. (S. multicaulis Vahl. Enum. and S. tricochlada Bentham) species from East Anatolian region (Turkey)","volume":"3","year":"2008","journal-title":"Int. J. Sci. Technol. Res."},{"key":"ref_9","first-page":"137","article-title":"An addition to the flora of Turkey: Salvia reuter\u0131ana (Lamiaceae), with contributions to its taxonomy","volume":"26","author":"Firat","year":"2020","journal-title":"Iran. J. Bot."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6593","DOI":"10.1021\/jf0608773","article-title":"Chemical composition and antifungal activity of Salvia macrochlamys and Salvia recognita essential oils","volume":"54","author":"Tabanca","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"ref_11","first-page":"18","article-title":"The chemical composition of Salvia verticillata L. subsp. verticillata from Turkey","volume":"4","author":"Tabanca","year":"2017","journal-title":"Nat. Volatiles Essent. Oils."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.chroma.2009.11.086","article-title":"Gas chromatographic-mass spectrometric analysis of volatiles obtained by four different techniques from Salvia rosifolia Sm. and evaluation for biological activity","volume":"1217","author":"Demirci","year":"2010","journal-title":"J. Chromatogr. A"},{"key":"ref_13","first-page":"89","article-title":"Characterization of essential oils of some Salvia species and their antimycobacterial activities","volume":"34","year":"2010","journal-title":"Turk. J. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jep.2010.11.061","article-title":"A novel wound healing ointment: A formulation of Hypericum perforatum oil and sage and oregano essential oils based on traditional Turkish knowledge","volume":"134","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4929","DOI":"10.1007\/s11694-021-01065-8","article-title":"Isolation of secondary metabolites of two endemic species: Salvia rosifolia Sm. and Salvia cerino-pruinosa Rech. f. var. elazigensis (Lamiaceae)","volume":"15","author":"Yener","year":"2021","journal-title":"J. Food Meas. Charact."},{"key":"ref_16","first-page":"1","article-title":"A new diterpene and other constituents Salvia multicaulis from Jordan","volume":"24","author":"Barhoumi","year":"2021","journal-title":"Nat. Prod. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"121","DOI":"10.4103\/1995-705X.95070","article-title":"Statins: Past and present","volume":"12","author":"Hajar","year":"2011","journal-title":"Heart Views."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.jep.2006.11.035","article-title":"Medicinal plants used in K\u0131rklareli Province (Turkey)","volume":"111","year":"2007","journal-title":"J. Ethnopharmacol."},{"key":"ref_19","first-page":"30","article-title":"An ethnobotanical study from Kars (Eastern) Turkey","volume":"4","year":"2011","journal-title":"Biodivers. Conserv."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.apsb.2013.06.001","article-title":"An ethnopharmacological investigation of medicinal Salvia plants (Lamiaceae) in China","volume":"3","author":"Li","year":"2013","journal-title":"Acta Pharm. Sin. B."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"484","DOI":"10.2183\/pjab.86.484","article-title":"A historical perspective on the discovery of statins","volume":"86","author":"Endo","year":"2010","journal-title":"Proc. Jpn. Acad."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/nm1008-1050","article-title":"A gift from nature: The birth of the statins","volume":"14","author":"Endo","year":"2008","journal-title":"Nat. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s10886-009-9646-0","article-title":"Antitermitic activities of abietane-type diterpenes from Taxodium distichum cones","volume":"35","author":"Kusumoto","year":"2009","journal-title":"J. Chem. Ecol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"7354","DOI":"10.1021\/jo00026a034","article-title":"A new abietane diterpene from Salvia wiedemannii Boiss","volume":"56","author":"Ulubelen","year":"1991","journal-title":"J. Org. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1248\/cpb.46.107","article-title":"Constituents of roots of Salvia deserta Schang. (Xinjiang-Danshen)","volume":"46","author":"Tezuka","year":"1998","journal-title":"Chem. Pharm. Bull."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.jpba.2009.04.012","article-title":"Isolation and analysis of bioactive diterpenoids in Salvia species (Salvia chionantha and Salvia kronenburgii) by micellar electrokinetic capillary chromatography","volume":"51","author":"Erim","year":"2010","journal-title":"J. Pharm. Biomed."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1002\/mrc.1245","article-title":"1H and 13C-NMR spectral assignments of some natural abietane diterpenoids","volume":"41","year":"2003","journal-title":"Magn. Reson. Chem."},{"key":"ref_28","first-page":"7","article-title":"The synthesis of (+)-pisiferol and (+)-pisiferal","volume":"56","author":"Takashi","year":"1983","journal-title":"Bull. Chem. Soc. Jpn."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1021\/np9700681","article-title":"Norditerpenoids and diterpenoids from Salvia multicaulis with antituberculous activity","volume":"60","author":"Ulubelen","year":"1997","journal-title":"J. Nat. Prod."},{"key":"ref_30","first-page":"195","article-title":"Antioxidant activity tests on novel triterpenoids from Salvia Macrochlamys","volume":"7","author":"Kolak","year":"2007","journal-title":"Arkivoc"},{"key":"ref_31","unstructured":"Erta\u015f, A., Top\u00e7u, G., Kolak, U., Temel, H., Yener, I., and Y\u0131lmaz, M.A. (2018). Screening of some Salvia (sage) species by HPLC-IT-TOF-MS, purification of their secondary metabolites, and determination of their anticancer effect. The Scientific and Technological Research Council of Turkey (T\u00dcB\u0130TAK), Project No: 114Z801."},{"key":"ref_32","first-page":"105","article-title":"Chemical constituents of Mentha longifolia subsp","volume":"9","author":"Ertas","year":"2015","journal-title":"noeana with antioxidant, anticholinesterase and antimicrobial activities. Rec. Nat. Prod."},{"key":"ref_33","first-page":"139","article-title":"Epidemiology and management of hyperlipidemia","volume":"23","author":"Karr","year":"2017","journal-title":"Am. J. Manag. Care."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/j.1472-8206.2004.00299.x","article-title":"Chemical, pharmacokinetic and pharmacodynamic properties of statins: An update","volume":"19","author":"Schachter","year":"2005","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10557-019-06904-x","article-title":"State of the art comprehensive review of individual statins, their differences, pharmacology, and clinical implications","volume":"33","author":"Azemawah","year":"2019","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s11883-019-0793-7","article-title":"Role of statin therapy in primary prevention of cardiovascular disease in elderly patients","volume":"21","author":"Strandberg","year":"2019","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1517\/14740338.2011.540568","article-title":"Statin-induced myopathy: A review and update","volume":"10","author":"Abd","year":"2011","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1097\/MOL.0000000000000172","article-title":"Statins and diabetes risk: How real is it and what are the mechanisms?","volume":"26","author":"Robinson","year":"2015","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.2174\/1381612820666141013134447","article-title":"Adverse effects of statins\u2014Myths and reality","volume":"21","author":"Simic","year":"2015","journal-title":"Curr. Pharm. Des."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1177\/2047487314550804","article-title":"Muscle-and skeletal-related side-effects of statins: Tip of the iceberg?","volume":"23","author":"Auer","year":"2016","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1517\/14740338.2012.712959","article-title":"Statin drug interactions and related adverse reactions","volume":"11","author":"Bellosta","year":"2012","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1080\/17512433.2019.1659133","article-title":"Statins and the potential for higher diabetes mellitus risk","volume":"12","author":"Yandrapalli","year":"2019","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1080\/14740338.2019.1615053","article-title":"Muscle and statins: From toxicity to the nocebo effect","volume":"18","author":"Climent","year":"2019","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1097\/FJC.0000000000000067","article-title":"Danhong injection inhibits the development of atherosclerosis in both Apoe\u2212\/\u2212 and Ldlr\u2212\/\u2212 mice","volume":"63","author":"Chen","year":"2014","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s11130-018-0668-z","article-title":"Peptides from chia present antibacterial activity and inhibit cholesterol synthesis","volume":"73","author":"Coelho","year":"2018","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5206","DOI":"10.1016\/j.ejmech.2011.08.012","article-title":"Discovery of a new class of HMG-CoA reductase inhibitor from Polyalthia longifolia as potential lipid lowering agent","volume":"46","author":"Sashidhara","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1007\/s00210-018-1518-0","article-title":"Pharmacokinetics, metabolism, bioavailability, tissue distribution and excretion studies of 16\u03b1-hydroxycleroda-3, 13 (14) Z-dien-15, 16-olide\u2014A novel HMG-CoA reductase inhibitor","volume":"391","author":"Laksman","year":"2018","journal-title":"Naunyn Schmiedebe. Arch. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/S0022-2275(20)32576-1","article-title":"Effect of a coffee lipid (cafestol) on cholesterol metabolism in human skin fibroblasts","volume":"39","author":"Halvorsen","year":"1998","journal-title":"J. Lipid Res."},{"key":"ref_49","first-page":"731","article-title":"Cholesterol biosynthesis inhibitors of microbial origin","volume":"33","author":"Kim","year":"2006","journal-title":"Nat. Prod. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s00253-002-0932-9","article-title":"Biosynthesis and biotechnological production of statins by filamentous fungi and application of these cholesterol-lowering drugs","volume":"58","author":"Manzoni","year":"2002","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1021\/acs.jnatprod.5b00331","article-title":"Lanostane triterpenes from the Tibetan medicinal mushroom Ganoderma leucocontextum and their inhibitory effects on HMG-CoA reductase and \u03b1-glucosidase","volume":"78","author":"Wang","year":"2015","journal-title":"J. Nat. Prod."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4538","DOI":"10.1016\/j.bmcl.2007.05.096","article-title":"Design and synthesis of hepatoselective, pyrrole-based HMG-CoA reductase inhibitors","volume":"17","author":"Pfefferkorn","year":"2007","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_53","first-page":"3","article-title":"Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments","volume":"27","author":"Adzhigirey","year":"2013","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.bmc.2005.12.032","article-title":"New insights about HERG blockade obtained from protein modeling, potential energy mapping, and docking studies","volume":"14","author":"Farid","year":"2006","journal-title":"Bioorg. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1021\/jm050540c","article-title":"Novel procedure for modeling ligand\/receptor induced fit effects","volume":"49","author":"Sherman","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1747-0285.2005.00327.x","article-title":"Use of an induced fit receptor structure in virtual screening","volume":"67","author":"Sherman","year":"2006","journal-title":"Chem. Biol. Drug. Des."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/2\/198\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:14:00Z","timestamp":1760134440000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/2\/198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,4]]},"references-count":56,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ph15020198"],"URL":"https:\/\/doi.org\/10.3390\/ph15020198","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,4]]}}}