Green Ultrasound-Assisted Extraction of Podophyllotoxin from Juniperus scopulorum Needles
Abstract
:1. Introduction
2. Materials and Methods
2.1. Plant Material
2.2. Chemicals
2.3. Grinding Approach
2.4. Ultrasound-Assisted Extraction (USAE) Optimization
2.5. Reference Solid/Liquid Extraction
2.6. High-Performance Liquid Chromatography (HPLC) Analysis
2.7. Experimental Design
2.8. Statistical Analysis
3. Results
3.1. Preliminary Single Factor Experiments
3.2. Development of a Multifactorial Approach
3.3. Variation of Podophyllotoxin Content in Different Varieties of Juniperus scopulorum
3.4. Comparison of the Optimized Protocol with the Reference Protocol
3.5. The Juniperus Extract Stability
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Canel, C.; Moraes, R.M.; Dayan, F.; Ferreira, D. Podophyllotoxin. Phytochemistry 2000, 54, 115–120. [Google Scholar] [CrossRef] [PubMed]
- Cragg, G.M.; Kingston, D.G. Anticancer Agents from Natural Products, 2nd ed.; CRC Press: Boca Raton, FL, USA, 2011; p. 97. [Google Scholar]
- Podwyssotzki, V. The active constituents of podophyllotoxin. Pharm. J. Trans. 1881, 12, 217–218. [Google Scholar]
- Podwyssotzki, V. On the active constituents of podophyllin. Am. J. Pharm. 1882, 12, 102–115. [Google Scholar]
- Podwyssotzki, V. Pharmakologische Studien uber Podophyllum peltatum. Arch. Exp. Path. Pharmakol. 1884, 13, 29–52. [Google Scholar] [CrossRef]
- Yu, X.; Che, Z.P.; Xu, H. Recent Advances in the Chemistry and Biology of Podophyllotoxins. Chem. Eur. J. 2016, 10, 1002–1006. [Google Scholar] [CrossRef]
- Stoll, A.; Renz, J.; Wartburg, A.V. The isolation of podophyllotoxin glucoside. J. Am. Chem. Soc. 1954, 76, 3103–3104. [Google Scholar] [CrossRef]
- Stoll, A.; von Wartburg, A.; Angliker, E.; Renz, J. The isolation of 40-Demethylpodophyllotoxin glucoside from rhizomes podophyllum emodi wall. J. Am. Chem. Soc. 1954, 76, 5004–5005. [Google Scholar] [CrossRef]
- Emmenggger, H.; Stahelin, H.; Rutschmann, J.; von Wartburg, A. Chemistry and Pharmacology of podophyllum glucosides and derivatives. I. Arzneim. 1961, 11, 327–333. [Google Scholar]
- Kuhn, M.; von Wartburg, A. Mitosis-inhibiting substances. XXI. Synthesis of epipodophyllotoxin b-D-glucopyranoside. Helv. Chim. Acta 1968, 51, 1631–1641. [Google Scholar] [CrossRef]
- Kuhn, M.; von Wartburg, A. Mitosis-inhibiting substances. Glycosidation process. II. Glycosides of 4”-demethylepipodophyllotoxin. Helv. Chim. Acta 1969, 52, 948–955. [Google Scholar] [CrossRef]
- Keller-Juslen, C.; Kuhn, M.; VonWartburg, A.; Staehelin, H. Synthesis and antimitotic activity of glycosidic lignan derivatives related to podophyllotoxin. J. Med. Chem. 1971, 14, 936–940. [Google Scholar] [CrossRef] [PubMed]
- Joel, S. The clinical pharmacology of etoposide. An update. Cancer Treat. Rev. 1996, 22, 179–221. [Google Scholar] [CrossRef] [PubMed]
- Stahelin, H.F.; von Wartburg, A. The chemical and biological route from podophyllotoxin glucoside to etoposide: Ninth cain memorial award lecture. Cancer Res. 1991, 51, 5–15. [Google Scholar] [PubMed]
- Gordaliza, M.; Garcia, P.A.; Miguel del Corral, J.M. Podophyllotoxin: Distribution, sources, applications, and new cytotoxic derivatives. Toxicon 2004, 44, 441–459. [Google Scholar] [CrossRef]
- Ardalani, H.; Avan, A.; Ghayour-Mobarhan, M. Podophyllotoxin: A novel potential natural anticancer agent. Avicenna J. Phytomed. 2017, 7, 285–294. [Google Scholar] [PubMed]
- Holm, B.; Sehested, M.; Jesen, P.B. Improved targeting of brain tumors using dexrazoxane rescue of topoisomerase II combined with supra-lethal doses of etoposide and teniposide. Clin. Cancer Res. 1998, 4, 1367–1373. [Google Scholar]
- Ekstrom, K.; Hoffman, K.; Linne, T.; Eriksoon, B.; Glimelius, B. Single-dose etoposide in advanced pancreatic and biliary cancer, a phase II study. Oncol. Rep. 1998, 5, 931–934. [Google Scholar] [CrossRef]
- Zi, C.T.; Yang, L.; Kong, Q.H.; Li, H.M.; Yang, X.Z.; Ding, Z.T.; Jiang, Z.H.; Hu, J.M.; Zhou, J. Glucoside derivatives of podophyllotoxin: Synthesis, physicochemical properties, and cytotoxicity. Drug Des. Dev. Ther. 2019, 13, 3683–3692. [Google Scholar] [CrossRef]
- Hammonds, T.R.; Denyer, S.P.; Jackson, D.E.; Irving, W.L. Studies to show that with podophyllotoxine the early replicative stages of herpes virus type 1 depend upon functional cytoplasmic microtubules. J. Med. Microbiol. 1996, 45, 167–172. [Google Scholar] [CrossRef]
- Chen, S.W.; Wang, Y.H.; Jin, Y.; Tian, X.; Zheng, Y.T.; Luo, D.Q.; Tu, Y.Q. Synthesis and anti-HIV-1 activities of novel podophyllotoxin derivatives. Bioorg. Med. Chem. Lett. 2007, 17, 2091–2095. [Google Scholar] [CrossRef]
- Maulin, P.; Eduardo, D.; Daniel, S.; Parag, D.; Ashwin, C.; Michael, B.; Roberto, C.; Gerard, C.J. Etoposide as salvage therapy for cytokine storm due to coronavirus disease 2019. Chest 2021, 159, E7–E11. [Google Scholar]
- Hartwell, J.L.; Schrecker, A.W. Components of Podophyllin. V. The Constitution of Podophyllotoxin. J. Am. Chem. Soc. 1951, 73, 2909–2916. [Google Scholar] [CrossRef]
- Purohit, M.C.; Bahuguna, R.; Maithani, U.C.; Purohit, A.N.; Rawat, M.S.M. Variation in podophylloresin and podophyllotoxin contents in different populations of Podophyllum hexandrum. Curr. Sci. India 1999, 77, 1078–1080. [Google Scholar]
- Li, H.; Cimino, S.K. Clinical impact of the etoposide injection shortage. J. Oncol. Pharm. Pract. 2020, 26, 187–192. [Google Scholar] [CrossRef] [PubMed]
- Hartwell, J.L.; Johnson, J.M.; Fitzgerald, D.B.; Belkin, M. Podophyllotoxin from Juniperus species savinin. J. Am. Chem. Soc. 1953, 75, 235–236. [Google Scholar] [CrossRef]
- Cushman, K.E.; Maqbool, M.; Gerard, P.D.; Bedir, E.; Lata, H.; Moraes, R.M. Variation of podophyllotoxin in leaves of Eastern red cedar (Juniperus virginiana). Planta Med. 2003, 69, 477–478. [Google Scholar]
- Gawde, A.; Cantrell, C.L.; Zheljazkov, V.D. Dual extraction of essential oil and podophyllotoxin from Juniperus virginiana. Ind. Crops Prod. 2009, 30, 276–280. [Google Scholar] [CrossRef]
- Gawde, A.; Zheljazkov, V.D.; Maddox, V.; Cantrell, C.L. Bioprospection of Eastern red cedar from nine physiographic regions in Mississippi. Ind. Crops Prod. 2009, 30, 59–64. [Google Scholar] [CrossRef]
- Cantrell, C.L.; Zheljazkov, V.D.; Osbrink, W.L.; Castro, A.; Maddox, V.; Craker, L.E.; Astatkie, T. Podophyllotoxin and essential oil profile of Juniperus and related species. Ind. Crops Prod. 2013, 43, 668–676. [Google Scholar] [CrossRef]
- Renouard, S.; Lopez, T.; Hendrawati, O.; Dupré, P.; Doussot, J.; Falguieres, A.; Ferroud, C.; Hagège, D.; Lamblin, F.; Lainé, E.; et al. Podophyllotoxin and deoxypodophyllotoxin in Juniperus bermudiana and 12 other Juniperus species: Optimization of extraction, method validation, and quantification. J. Agric. Food Chem. 2011, 59, 8101–8107. [Google Scholar] [CrossRef]
- Och, M.; Och, A.; Cie’sla, L.; Kubrak, T.; Pecio, L.; Stochmal, A.; Kocki, J.; Bogucka-Kocka, A. Study of cytotoxic activity, podophyllotoxin, and deoxypodophyllotoxin content in selected Juniperus species cultivated in Poland. Pharm. Biol. 2015, 53, 831–837. [Google Scholar] [CrossRef] [PubMed]
- Ivanova, D.I.; Nedialkov, P.T.; Tashev, A.N.; Olech, M.; Nowak, R.; Ilieva, Y.E.; Kokanova-Nedialkova, Z.K.; Atanasova, T.N.; Angelov, G.; Najdenski, H.M. Junipers of various origins as potential sources of the anticancer drug precursor podophyllotoxin. Molecules 2021, 26, 5179. [Google Scholar] [CrossRef] [PubMed]
- Kusari, S.; Zühlke, S.; Spiteller, M. Chemometric evaluation of the anti-cancer pro-drug podophyllotoxin and potential therapeutic analogues in Juniperus and Podophyllum species. Phytochem. Anal. 2011, 22, 128–143. [Google Scholar] [CrossRef]
- Woo, K.W.; Choi, S.U.; Park, J.C.; Lee, K.R. A new lignan glycoside from Juniperus rigida. Arch. Pharm. Res. 2011, 34, 2043–2049. [Google Scholar] [CrossRef]
- Han, J.W.; Shim, D.W.; Shin, W.Y.; Kim, M.K.; Shim, E.J.; Sun, X.; Koppula, S.; Kim, T.J.; Kang, T.B.; Lee, K.H. Juniperus rigida Sieb. extract inhibits inflammatory responses via attenuation of TRIF-dependent signaling and inflammasome activation. J. Ethnopharmacol. 2016, 190, 91–99. [Google Scholar] [CrossRef] [PubMed]
- Liu, Z.; Wang, D.; Li, D.; Zhang, S. Quality evaluation of Juniperus rigida Sieb. et Zucc. based on phenolic profiles, bioactivity, and HPLC fingerprint combined with chemometrics. Front. Pharmacol. 2017, 8, 198. [Google Scholar] [CrossRef] [PubMed]
- Zheljazkov, V.D.; Cantrell, C.L.; Donega, M.A.; Astatkie, T.; Heidel, B. Podophyllotoxin concentration in Junipers in the Big Horn Mountains in Wyoming. HortScience 2012, 47, 1696–1697. [Google Scholar] [CrossRef]
- Xu, S.; Li, X.; Liu, S.; Tian, P.; Li, D. Juniperus sabina L. as a source of podophyllotoxins: Extraction optimization and anticholinesterase activities. Int. J. Mol. Sci. 2022, 23, 10205. [Google Scholar] [CrossRef]
- Fu, X.; Wang, D.; Belwal, T.; Xie, J.; Xu, Y.; Zou, L.; Zhang, L.; Luo, Z. Natural deep eutectic solvent enhanced pulse-ultrasonication assisted extraction as a multistability protective and efficient green strategy to extract anthocyanin from blueberry pomace. LWT 2021, 144, 111220. [Google Scholar] [CrossRef]
- Yusoff, I.; Taher, Z.; Rahmat, Z.; Chua, L. A review of ultrasound-assisted extraction for plant bioactive compounds: Phenolics, flavonoids, thymols, saponins and proteins. Food Res. Int. 2022, 157, 111268. [Google Scholar] [CrossRef]
- Miller, D.L.; Pislaru, S.V.; Greenleaf, J.E. Sonoporation: Mechanical DNA delivery by ultrasonic cavitation. Somat. Cell Mol. Gen. 2002, 27, 115–134. [Google Scholar] [CrossRef]
- Karshafian, R.; Bevan, P.D.; Williams, R.; Samac, S.; Burns, P.N. Sonoporation by ultrasound-activated microbubble contrast agents: Effect of acoustic exposure parameters on cell membrane permeability and cell viability. Ultrasound Med. Biol. 2009, 35, 847–860. [Google Scholar] [CrossRef] [PubMed]
- Ohta, S.; Suzuki, K.; Miyagawa, S.; Ogino, Y.; Villacorte, M.; Wada, Y.; Yamada, G. Sonoporation in developmental biology. In Electroporation and Sonoporation in Developmental Biology; Nakamura, H., Ed.; Springer: Tokyo, Japan, 2009; pp. 317–326. [Google Scholar]
- Gang, D.; Wang, J.; Dudareva, N.; Nam, K.; Simon, J.; Lewinsohn, E.; Pichersky, E. An investigation of the storage and biosynthesis of phenylpropenes in sweet basil. Plant. Physiol. 2001, 125, 539–555. [Google Scholar] [CrossRef] [PubMed]
- Khoddami, A.; Wilkes, M.A.; Roberts, T.H. Techniques for analysis of plant phenolic compounds. Molecules 2013, 18, 2328–2375. [Google Scholar] [CrossRef] [PubMed]
- Shen, L.; Pang, S.; Zhong, M.; Sun, Y.; Qayum, A.; Liu, Y.; Rashid, A.; Xu, B.; Liang, Q.; Ma, H.; et al. A comprehensive review of ultrasonic assisted extraction (UAE) for bioactive components: Principles, advantages, equipment, and combined technologies. Ultrason. Sonochem. 2023, 101, 106646. [Google Scholar] [CrossRef]
- Zhao, S.; Baik, O. Application of ultrasound as pretreatment for extraction of podophyllotoxin from rhizomes of Podophyllum peltatum. Ultrason. Sonochem. 2012, 19, 22–31. [Google Scholar] [CrossRef]
- Corbin, C.; Fidel, T.; Leclerc, E.A.; Barakzoy, E.; Sagot, N.; Falguiéres, A.; Renouard, S.; Blondeau, J.P.; Ferroud, C.; Doussot, J.; et al. Development and validation of an efficient ultrasound assisted extraction of phenolic compounds from flax (Linum usitatissimum L.) seeds. Ultrason. Sonochem. 2015, 26, 176–185. [Google Scholar] [CrossRef]
- Soria, A.C.; Villamiel, M. Effect of ultrasound on the technological properties and bioactivity of food: A review. Trends Food Sci. Technol. 2010, 21, 323–331. [Google Scholar] [CrossRef]
- Lavilla, I.; Bendicho, C. Fundamentals of ultrasound-assisted extraction. In Water Extraction of Bioactive Compounds; González, H.D., González Muñoz, M.J., Eds.; Elsevier: Amsterdam, The Netherlands, 2017; pp. 291–316. [Google Scholar]
- Medina-Torres, N.; Ayora-Talavera, T.; Espinosa-Andrews, H.; Sánchez-Contreras, A.; Pacheco, N. Ultrasound assisted extraction for the recovery of phenolic compounds from vegetable sources. Agronomy 2017, 7, 47. [Google Scholar] [CrossRef]
- Toma, M.; Vinatoru, M.; Paniwnyk, L.; Mason, T. Investigation of the effects of ultrasound on vegetal tissues during solvent extraction. Ultrason. Sonochem. 2001, 8, 137–142. [Google Scholar] [CrossRef]
- Vinatoru, M. An overview of the ultrasonically assisted extraction of bioactive principles from herbs. Ultrason. Sonochem. 2001, 8, 303–313. [Google Scholar] [CrossRef] [PubMed]
- Tabaraki, R.; Nateghi, A. Optimization of ultrasonic-assisted extraction of natural antioxidants from rice bran using response surface methodology. Ultrason. Sonochem. 2011, 18, 1279–1286. [Google Scholar] [CrossRef] [PubMed]
- Tchabo, W.; Ma, Y.; Engmann, F.N.; Zhang, H. Ultrasound-assisted enzymatic extraction (UAEE) of phytochemical compounds from mulberry (Morus nigra) must and optimization study using response surface methodology. Ind. Crops Prod. 2015, 63, 214–225. [Google Scholar] [CrossRef]
- Mason, T.; Lorimer, J. General principles. In Applied Sonochemistry: Uses of Power Ultrasound in Chemistry and Processing; Mason, T.J., Lorimer, J.P., Eds.; Wiley: Weinheim, Germany, 2002; pp. 25–74. [Google Scholar]
- Santos, H.; Lodeiro, C.; Capelo-Martínez, J. The power of ultrasound. In Ultrasound in Chemistry: Analytical Applications; Capelo-Martínez, J.L., Ed.; Wiley: Weinheim, Germany, 2009; pp. 1–16. [Google Scholar]
- Shirsath, S.; Sonawane, S.; Gogate, P. Intensification of extraction of natural products using ultrasonic irradiations—A review of current status. Chem. Eng. Process. Process Intensif. 2012, 53, 10–23. [Google Scholar] [CrossRef]
- Peanparkdee, M.; Patrawatt, J.; Iwamoto, S. Effects of extraction conditions on phenolic content, anthocyanin content and antioxidant activity of bran extracts from Thai rice cultivars. J. Cereal Sci. 2019, 86, 86–91. [Google Scholar] [CrossRef]
- Zainol, M.; Mohd Subri, I.; Zamri, I.; Mohd Zin, Z.; Fisal, A.; Mamat, H. Antioxidative properties and proximate analysis of spent coffee ground (SCG) extracted using ultrasonic methanol assisted technique as a potential functional food ingredient. Food Res. 2020, 4, 636–644. [Google Scholar] [CrossRef]
- Bedir, E.; Tellez, M.; Lata, H.; Khan, I.; Cushman, K.E.; Moraes, R.M. Post-harvest and scale-up extraction of American mayapple leaves for podophyllotoxin production. Ind. Crops Prod. 2006, 24, 3–7. [Google Scholar] [CrossRef]
- Renouard, S.; Corbin, C.; Drouet, S.; Medvedec, B.; Doussot, J.; Colas, C.; Maunit, B.; Bhambra, A.; Gontier, E.; Jullian, N.; et al. Investigation of Linum flavum (L.) hairy root cultures for the production of anticancer aryltetralin lignans. Int. J. Mol. Sci. 2018, 19, 990. [Google Scholar] [CrossRef]
- Garros, L.; Drouet, S.; Corbin, C.; Decourtil, C.; Fidel, T.; Lebas de Lacour, J.; Leclerc, E.A.; Renouard, S.; Tungmunnithum, D.; Doussot, J.; et al. Insight into the influence of cultivar type, cultivation year, and site on the lignans and related phenolic profiles, and the health-promoting antioxidant potential of flax (Linum usitatissimum L.) seeds. Molecules 2018, 23, 2636. [Google Scholar] [CrossRef]
- Cushman, K.E.; Moraes, R.M.; Gerard, P.D.; Bedir, E.; Silva, B.; Khan, I.A. Frequency and timing of leaf removal affect growth and podophyllotoxin content of Podophyllum peltatum in full sun. Planta Med. 2006, 72, 824–829. [Google Scholar] [CrossRef]
Independent Variable | Code Unit | Coded Variable Level | ||
---|---|---|---|---|
−1 | 0 | 1 | ||
Ethanol concentration (% v/v) | X1 | 60 | 75 | 90 |
Incubation duration (min) | X2 | 30 | 55 | 80 |
Temperature (°C) | X3 | 40 | 60 | 80 |
Run ID | Run Order | X1 | X2 | X3 | PT (mg/g DW) |
---|---|---|---|---|---|
Obs1 | 11 | −1 | −1 | 0 | 5.9913053 |
Obs2 | 6 | 1 | −1 | 0 | 6.51152504 |
Obs3 | 9 | −1 | 1 | 0 | 6.69284701 |
Obs4 | 15 | 1 | 1 | 0 | 5.72977268 |
Obs5 | 14 | −1 | 0 | −1 | 6.20516809 |
Obs6 | 4 | 1 | 0 | −1 | 6.48178819 |
Obs7 | 12 | −1 | 0 | 1 | 5.83502077 |
Obs8 | 10 | 1 | 0 | 1 | 6.09834046 |
Obs9 | 17 | 0 | −1 | −1 | 6.40098953 |
Obs10 | 8 | 0 | 1 | −1 | 5.80521013 |
Obs11 | 5 | 0 | −1 | 1 | 5.84521745 |
Obs12 | 18 | 0 | 1 | 1 | 6.25163654 |
Obs13 | 3 | 0 | 0 | 0 | 7.07106035 |
Obs14 | 1 | 0 | 0 | 0 | 6.88392753 |
Obs15 | 16 | 0 | 0 | 0 | 7.13525193 |
Obs16 | 2 | 0 | 0 | 0 | 6.77948881 |
Obs17 | 13 | 0 | 0 | 0 | 7.01239831 |
Obs18 | 7 | 0 | 0 | 0 | 6.79463394 |
Source | Value | SD | t | Pr > |t| |
---|---|---|---|---|
Constant | 6.946 | 0.077 | 90.230 | <0.0001 |
X1 | 0.012 | 0.067 | 0.182 | 0.860 |
X2 | −0.034 | 0.067 | −0.505 | 0.627 |
X3 | −0.108 | 0.067 | −1.618 | 0.144 |
X12 | −0.318 | 0.090 | −3.520 | 0.008 |
X1X2 | −0.371 | 0.094 | −3.933 | 0.004 |
X1X3 | −0.003 | 0.094 | −0.035 | 0.973 |
X22 | −0.397 | 0.090 | −4.398 | 0.002 |
X2X3 | 0.251 | 0.094 | 2.657 | 0.029 |
X32 | −0.473 | 0.090 | −5.243 | 0.001 |
Source | Sum of Square | DDL | Mean of Square | F-Value | p-Value |
---|---|---|---|---|---|
Model | 3.462 | 9 | 0.385 | 10.819 | 0.0013 |
Error | 0.284 | 8 | 0.036 | ||
Total corrected | 3.747 | 17 | |||
R2 | 0.924 | ||||
R2 adjusted | 0.839 | ||||
CV% | 1.79 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Verret, C.; Rakotondramavo, A.; Renouard, S. Green Ultrasound-Assisted Extraction of Podophyllotoxin from Juniperus scopulorum Needles. Appl. Sci. 2023, 13, 12194. https://doi.org/10.3390/app132212194
Verret C, Rakotondramavo A, Renouard S. Green Ultrasound-Assisted Extraction of Podophyllotoxin from Juniperus scopulorum Needles. Applied Sciences. 2023; 13(22):12194. https://doi.org/10.3390/app132212194
Chicago/Turabian StyleVerret, Catherine, Anja Rakotondramavo, and Sullivan Renouard. 2023. "Green Ultrasound-Assisted Extraction of Podophyllotoxin from Juniperus scopulorum Needles" Applied Sciences 13, no. 22: 12194. https://doi.org/10.3390/app132212194
APA StyleVerret, C., Rakotondramavo, A., & Renouard, S. (2023). Green Ultrasound-Assisted Extraction of Podophyllotoxin from Juniperus scopulorum Needles. Applied Sciences, 13(22), 12194. https://doi.org/10.3390/app132212194