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DOI: 10.1055/a-1738-5648
A Development Strategy of Tailor-made Natural Deep Eutectic Solvents for the Enhanced Extraction of Hydroxynaphthoquinones from Alkanna tinctoria Roots[ # ]
Supported by: H2020 Marie Skłodowska-Curie Actions 721635
Abstract
Natural hydroxynaphthoquinone enantiomers (HNQs) are well-described pharmaceutical and cosmeceutical agents especially present in the roots of Alkanna tinctoria (L.) Tausch, a species native to the Mediterranean region. In this work, eco-friendly natural deep eutectic solvents (NaDESs) were developed for the selective extraction of these compounds. An extensive screening was performed using more than sixty tailor-made NaDESs. The impact of the intrinsic physicochemical properties on the HNQs extraction efficiency as well as the specificity towards the different enantiomeric pairs was thoroughly investigated. As a result of a multivariate analysis and of the one factor-a-time solvent optimization, the eutectic mixture composed of levulinic acid and glucose (LeG) using a molar ratio of 5 : 1 (molHBA : molHBD) and 20% of water (w/w) was found as the most appropriate mixture for the highest extraction efficiency of HNQs. Further optimization of the extraction process was attained by response surface methodology, using a temperature of 45 °C, a solid-to-liquid ratio of 30 mg/mL, and an extraction time of 50 min. A maximum extraction output of 41.72 ± 1.04 mg/g was reached for HNQs, comparable to that of the commonly used organic solvents. A solid-phase extraction step was also proposed for the recovery of HNQs and for NaDESs recycling. Our results revealed NaDESs as a highly customizable class of green solvents with remarkable capabilities for the extraction of HNQs.
Key words
Natural Deep Eutectic Solvent (NaDES) - eco-friendly - Alkanna tinctoria - Boraginaceae - hydroxynaphthoquinone enantiomers# Dedicated to Professor Dr. A. Douglas Kinghorn on the occasion of his 75th birthday.
Supporting Information
- Supporting Information
1H-NMR and HRMS spectra of the seven isolated hydroxynaphthoquinone enantiomers: AS, AcAS, DeoxyAS, IsoBAS, DimetAAS, and IsoVAS-MetBAS (Figs 1S–12S), physicochemical properties of COaS based-, BOaS based-, POaS based-, OaS based-, and OaAG based-NaDESs (Tables 1S–5S), validation of the quantification method as linearity, specificity, limit of detection, limit of quantification, and intra- and inter-day precision (Tables 6S–9S), biplots of the principal component analysis of the extracts from A. tinctoria for COaS based-, BOaS based-, OaS based-, and OaAG based-NaDES categories separately (Fig. 14S), effect of molar ratio and water content on the amount of AS, AcAS, DeoxyAS, IsoBAS, DimetAAS, and IsoVAS-MetBAS extracted from A. tinctoria roots powder (Figs 15S and 16S), and BBD based statistical optimization results and response surface plots of the seven hydroxynaphthoquinone enantiomers (Tables 10S–11S and Fig. 17S) are available as Supporting information.
Publication History
Received: 16 September 2021
Accepted after revision: 12 January 2022
Accepted Manuscript online:
12 January 2022
Article published online:
11 July 2022
© 2022. Thieme. All rights reserved.
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References
- 1 Papageorgiou V, Assimopoulou A, Ballis A. Alkannins and shikonins: A new class of wound healing agents. Curr Med Chem 2008; 15: 3248-3267 DOI: 10.2174/092986708786848532.
- 2 Singh B, Sharma M, Meghwal P, Sahu P, Singh S. Anti-inflammatory activity of shikonin derivatives from Arnebia hispidissima . Phytomedicine 2003; 10: 375-380 DOI: 10.1078/0944-7113-00262.
- 3 Sahakyan N, Petrosyan M, Trchounian A. The activity of Alkanna species in vitro culture and intact plant extracts against antibiotic resistant bacteria. Curr Pharm Des 2019; 25: 1861-1865 DOI: 10.2174/1381612825666190716112510.
- 4 Zhang X, Wang R, Zhou W, Xiao S, Meng Q, Li S. Antitumor activity of DMAKO-05, a novel shikonin derivative, and its metabolism in rat liver microsome. AAPS PharmSciTech 2015; 16: 259-266 DOI: 10.1208/s12249-014-0217-5.
- 5 Sankawa U, Ebizuka Y, Miyazaki T, Isomura Y, Otsuka H. Antitumor activity of shikonin and its derivatives. Chem Pharm Bull 1977; 25: 2392-2395 DOI: 10.1248/cpb.25.2392.
- 6 Cui J, Zhang X, Huang G, Zhang Q, Dong J, Sun G, Meng Q, Li S. DMAKO-20 as a new multitarget anticancer prodrug activated by the tumor specific CYP1B1 enzyme. Mol Pharm 2019; 16: 409-421 DOI: 10.1021/acs.molpharmaceut.8b01062.
- 7 Fan C, Lim L, Loh S, Ying Lim K, Upton Z, Leavesley D. Application of “macromolecular crowding” in vitro to investigate the naphthoquinones shikonin, naphthazarin and related analogues for the treatment of dermal scars. Chem Biolo Interact 2019; 310: 108747 DOI: 10.1016/j.cbi.2019.108747.
- 8 Papageorgiou V, Assimopoulou A, Couladouros E, Hepworth D, Nicolaou K. The chemistry and biology of alkannin, shikonin, and related naphthazarin natural products. Angew Chem Int Ed Engl 1999; 38: 270-301 DOI: 10.1002/(SICI)1521-3773(19990201)38:3<270::AID-ANIE270>3.0.CO;2-0.
- 9 Babula P, Adam V, Havel L, Kizek R. Noteworthy secondary metabolites naphthoquinones-their occurrence, pharmacological properties and analysis. Curr Pharm Anal 2009; 5: 47-68 DOI: 10.2174/157341209787314936.
- 10 Ruesgas-Ramón M, Figueroa-Espinoza M, Durand E. Application of deep eutectic solvents (DES) for phenolic compounds extraction: overview, challenges, and opportunities. J Agric Food Chem 2017; 65: 3591-3601 DOI: 10.1021/acs.jafc.7b01054.
- 11 Dai Y, van Spronsen J, Witkamp G, Verpoorte R, Choi Y. Ionic liquids and deep eutectic solvents in natural products research: mixtures of solids as extraction solvents. J Nat Prod 2013; 76: 2162-2173 DOI: 10.1021/np400051w.
- 12 Santana A, Mora-Vargas J, Guimarães T, Amaral C, Oliveira A, Gonzalez M. Sustainable synthesis of natural deep eutectic solvents (NADES) by different methods. J Mol Liq 2019; 293: 111452 DOI: 10.1016/j.molliq.2019.111452.
- 13 Choi Y, Spronsen J, Dai Y, Verberne M, Hollmann F, Arends I, Witkamp G, Verpoorte R. Are natural deep eutectic solvents the missing link in understanding cellular metabolism and physiology?. Plant Physiol 2011; 156: 1701-1705 DOI: 10.1104/pp.111.178426.
- 14 Fraige K, Arrua R, Sutton A, Funari C, Cavalheiro A, Hilder E, Bolzani V. Using natural deep eutectic solvents for the extraction of metabolites in Byrsonima intermedia leaves. J Sep Sci 2019; 42: 591-597 DOI: 10.1002/jssc.201800905.
- 15 Ahmad I, Pertiwi A, Kembaren Y, Rahman A. Application of natural deep eutectic solvent-based ultrasonic assisted extraction of total polyphenolic and caffeine content from coffee beans (Coffea Beans L.) for instant food products. J App Pharm Sci 2018; 8: 138-143 DOI: 10.7324/JAPS.2018.8819.
- 16 Ivanović M, Alañón M, Arráez-Román D, Segura-Carretero A. Enhanced and green extraction of bioactive compounds from Lippia citriodora by tailor-made natural deep eutectic solvents. Food Res Int 2018; 111: 67-76 DOI: 10.1016/j.foodres.2018.05.014.
- 17 Huang Y, Feng F, Jiang J, Qiao Y, Wu T, Voglmeir J, Chen Z. Green and efficient extraction of rutin from tartary buckwheat hull by using natural deep eutectic solvents. Food Chem 2017; 221: 1400-1405 DOI: 10.1016/j.foodchem.2016.11.013.
- 18 Bosiljkov T, Dujmić F, Cvjetko Bubalo M, Hribar J, Vidrih R, Brnčić M, Zlatic E, Radojčić Redovniković I, Jokić S. Natural deep eutectic solvents and ultrasound-assisted extraction: Green approaches for extraction of wine lees anthocyanins. Food Bioprod Process 2017; 102: 195-203 DOI: 10.1016/j.fbp.2016.12.005.
- 19 Bajkacz S, Adamek J. Evaluation of new natural deep eutectic solvents for the extraction of isoflavones from soy products. Talanta 2017; 168: 329-335 DOI: 10.1016/j.talanta.2017.02.065.
- 20 Wu Y, Wu P, Li Y, Liu T, Zhang L, Zhou Y. Natural deep eutectic solvents as new green solvents to extract anthraquinones from Rheum palmatum L. RSC Adv 2018; 8: 15069-15077 DOI: 10.1039/C7RA13581E.
- 21 Wang T, Jiao J, Gai Q, Wang P, Guo N, Niu L, Fu Y. Enhanced and green extraction polyphenols and furanocoumarins from Fig (Ficus carica L.) leaves using deep eutectic solvents. J Pharm Biomed Anal 2017; 145: 339-345 DOI: 10.1016/j.jpba.2017.07.002.
- 22 Liu Y, Friesen J, McAlpine J, Lankin D, Chen S, Pauli G. Natural deep eutectic solvents: Properties, applications, and perspectives. J Nat Prod 2018; 81: 679-690 DOI: 10.1021/acs.jnatprod.7b00945.
- 23 Dai Y, Witkamp G, Verpoorte R, Choi Y. Tailoring properties of natural deep eutectic solvents with water to facilitate their applications. Food Chem 2015; 187: 14-19 DOI: 10.1016/j.foodchem.2015.03.123.
- 24 Gullón P, Gullón B, Romaní A, Rocchetti G, Lorenzo J. Smart advanced solvents for bioactive compounds recovery from agri-food by-products: A review. Trends Food Sci & Technol 2020; 101: 182-197 DOI: 10.1016/j.tifs.2020.05.007.
- 25 Assimopoulou A, Sturm S, Stuppner H, Papageorgiou V. Preparative isolation and purification of alkannin/shikonin derivatives from natural products by high-speed counter-current chromatography. Biomed Chromatogr 2009; 23: 182-198 DOI: 10.1002/bmc.1101.
- 26 Zhang Y, Xiao S, Li X, Zeng X, Cheng Y. Ionization of shikonin derivatives using negative-ion electrospray mass spectrometry: [M – H]- versus [M + e]•-. J Mass Spectrom 2012; 47: 581-585 DOI: 10.1002/jms.2045.
- 27 Sagratini G, Cristalli G, Giardinà D, Gioventù G, Maggi F, Ricciutelli M, Vittori S. Alkannin/shikonin mixture from roots of Onosma echioides (L.): Extraction method study and quantification. J Sep Sci 2008; 31: 945-952 DOI: 10.1002/jssc.200700408.
- 28 Husson F, Josse J, Le S, Mazet J. FactoMineR: Multivariate Exploratory Data Analysis and Data Mining. R package version 2.3. Accessed December 11, 2020 at: https://CRAN.R-project.org/package=FactoMineR
- 29 Wickham H. ggplot2: Create Elegant Data Visualisations Using the Grammar of Graphics. R package version 3.3.2. Accessed June 25, 2021 at: https://CRAN.R-project.org/package=ggplot2
- 30 Mendiburu F. Accessed June 06, 2021 at: https://CRAN.Rproject.org/package=agricolae//