Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000058.xml
Planta Med 2023; 89(11): 1063-1073
DOI: 10.1055/a-2063-5265
DOI: 10.1055/a-2063-5265
Biological and Pharmacological Activity
Original Papers
Anti-viral and Anti-inflammatory Isoflavonoids from Ukrainian Iris aphylla Rhizomes: Structure-Activity Relationship Coupled with ChemGPS-NP Analysis
The research was supported by grants from the National Science and Technology Council, Taiwan (111-2320-B-037-007 awarded to M. K. for chemical analysis and logistics; 111-2321-B-255-001, 111-2321-B-182 – 001, 109-2320-B-650-001-MY3, 109-2327-B-255-001, and 109-2327-B-182-002 awarded to T.-L. H. for bioactivity assays and instrumentation; 109-2320-B-037-004-MY3 awarded to B.-H. C. for bioactivity assays and analysis). This study was also supported by a grant from the Kaohsiung Medical University Research Foundation (KMU-Q112 006) awarded to M. K. for chemical analysis; Chang Gung Memorial Hospital (CMRPF1M0131-2, CMRPF1M0101-2, CMRPF1L0071, and CORPF1L0011) and Chang Gung University of Science and Technology (ZRRPF3L0091) awarded to T.-L. H. for bioactivity assays and technical support.
Abstract
Dried Iris rhizomes have been used in Chinese and European traditional medicine for the treatment of various diseases such as bacterial infections, cancer, and inflammation, as well as for being astringent, laxative, and diuretic agents. Eighteen phenolic compounds including some rare secondary metabolites, such as irisolidone, kikkalidone, irigenin, irisolone, germanaism B, kaempferol, and xanthone mangiferin, were isolated for the first time from Iris aphylla rhizomes. The hydroethanolic Iris aphylla extract and some of its isolated constituents showed protective effects against influenza H1N1 and enterovirus D68 and anti-inflammatory activity in human neutrophils. The promising anti-influenza effect of apigenin (13, almost 100% inhibition at 50 µM), kaempferol (14, 92%), and quercetin (15, 48%) were further confirmed by neuraminidase inhibitory assay. Irisolidone (1, almost 100% inhibition at 50 µM), kikkalidone (5, 93%), and kaempferol (14, 83%) showed promising anti-enterovirus D68 activity in vitro. The identified compounds were plotted using ChemGPS-NP to correlate the observed activity of the isolated phenolic compounds with the in-house database of anti-influenza and anti-enterovirus agents. Our results indicated that the hydroethanolic Iris aphylla extract and Iris phenolics hold the potential to be developed for the management of seasonal pandemics of influenza and enterovirus infections.
Key words
Iris aphylla - Iris hungarica - Iridaceae - isoflavones - enterovirus - influenza - neutrophilic inflammation - ChemGPS-NPSupporting Information
- Supporting Information
The following file is available free of charge.
Figures and tables describing NMR, spectroscopic, and MS data of isolated compounds, complete anti-viral data (influenza H1N1, enterovirus D68), and ChemGPS-NP in-house database (PDF).
Publication History
Received: 14 July 2022
Accepted after revision: 23 March 2023
Accepted Manuscript online:
28 March 2023
Article published online:
05 June 2023
© 2023. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Wang C, Wang Z, Wang G, Lau JY, Zhang K, Li W. COVID-19 in early 2021: Current status and looking forward. Signal Transduct Target Ther 2021; 6: 114-128
- 2 Woolf SH, Chapman DA, Sabo RT, Zimmerman EB. Excess deaths from COVID-19 and other causes in the US, March 1, 2020, to January 2, 2021. JAMA 2021; 325: 1786-1789
- 3 United Nationn. Coronavirus global health emergency. Accessed February 13, 2022 at: https://www.un.org/en/coronavirus
- 4 World Health Organization. Coronavirus disease (COVID-19) pandemic. Accessed February 13, 2022 at: https://www.who.int/
- 5 Khanna M, Kumar P, Choudhary K, Kumar B, Vijayan VK. Emerging influenza virus: A global threat. J Biosci 2008; 33: 475-482
- 6 Holm-Hansen CC, Midgley SE, Fischer TK. Global emergence of enterovirus D68: A systematic review. Lancet Infect Dis 2016; 16: e64
- 7 Hussain M, Galvin HD, Haw TY, Nutsford AN, Husain M. Drug resistance in influenza A virus: The epidemiology and management. Infect Drug Resist 2017; 10: 121-134
- 8 Sethy B, Hsieh CF, Lin TJ, Hu PY, Chen YL, Lin CY, Tseng SN, Horng JT, Hsieh PW. Design, synthesis, and biological evaluation of itaconic acid derivatives as potential anti-influenza agents. J Med Chem 2019; 62: 2390-2403
- 9 Moscona A. Neuraminidase inhibitors for influenza. N Engl J Med 2005; 353: 1363-1373
- 10 McKimm-Breschkin JL. Influenza neuraminidase inhibitors: Antiviral action and mechanisms of resistance. Influenza Other Respir Viruses 2013; 7: 25-36
- 11 Korkmaz B, Horwitz MS, Jenne DE, Gauthier F. Neutrophil elastase, proteinase 3, and cathepsin G as therapeutic targets in human diseases. Pharmacol Rev 2010; 62: 726-759
- 12 Chiang CC, Korinek M, Cheng WJ, Hwang TL. Targeting neutrophils to treat acute respiratory distress syndrome in coronavirus disease. Front Pharmacol 2020; 11: 572009-572023
- 13 Drugs.com. Find Drugs & Conditions. Accessed February 13, 2022 at: https://www.drugs.com/
- 14 European Medical Agency. Covid-19 pandemic. Accessed February 13, 2022 at: https://www.ema.europa.eu/en
- 15 U.S. Food & Drugs. Accessed February 13, 2022 at: https://www.fda.gov/drugs
- 16 Compendium. Drugs. Accessed February 13, 2022 at: https://compendium.com.ua/
- 17 Wróblewska A, Brzosko E, Czarnecka B, Nowosielski J. High levels of genetic diversity in populations of Iris aphylla L. (Iridaceae), an endangered species in Poland. Bot J Linn Soc 2003; 142: 65-72
- 18 Marinescu VM, Alexiu V. Iris aphylla L. ssp. hungarica critically endangered taxon in Europa. CTNS 2013; 2: 96-99
- 19 Mykhailenko O, Ivanauskas L, Bezruk I, Lesyk R, Georgiyants V. Comparative investigation of amino acids content in the dry extracts of Juno bucharica, Gladiolus hybrid zefir, Iris hungarica, Iris variegata and Crocus sativus raw materials of Ukrainian flora. Sci Pharm 2020; 88: 8-21
- 20 Mykhailenko O, Gudžinskas Z, Kovalyov V, Desenko V, Ivanauskas L, Bezruk I, Georgiyants V. Effect of ecological factors on the accumulation of phenolic compounds in Iris species from Latvia, Lithuania and Ukraine. Phytochem Anal 2020; 31: 1-19
- 21 Mykhailenko O, Korinek M, Ivanauskas L, Bezruk I, Myhal A, Petrikaitė V, El-Shazly M, Yen CH, Chen BH, Georgiyants V, Hwang TL. Qualitative and quantitative analysis of Ukrainian Iris species: A fresh look on their antioxidant content and biological activities. Molecules 2020; 25: 4588
- 22 Mykhailenko O, Kovalyov V, Kovalyov S, Krechun A. Isoflavonoids from the rhizomes of Iris hungarica and antibacterial activity of the dry rhizomes extract. Ars Pharm 2017; 58: 39-45
- 23 Larsson J, Gottfries J, Muresan S, Backlund A. ChemGPS-NP: Tuned for navigation in biologically relevant chemical space. J Nat Prod 2007; 70: 789-794
- 24 Korinek M, Tsai YH, El-Shazly M, Lai KH, Backlund A, Wu SF, Lai WC, Wu TY, Chen SL, Wu YC, Cheng YB, Hwang TL, Chen BH, Chang FR. Anti-allergic hydroxy fatty acids from Typhonium blumei explored through ChemGPS-NP. Front Pharmacol 2017; 8: 356-363
- 25 Ibrahim SR, Mohamed GA, Al-Musayeib NM. New constituents from the rhizomes of Egyptian Iris germanica L. Molecules 2012; 17: 2587-2598
- 26 Buch SM, Mir FA, Rehman S, Qurishi MA, Banday JA. Irigenin – an isoflavone: A brief study on structural and optical properties. Eur Phys J Appl Phys 2013; 62: 31201-31205
- 27 Ayatollahi SAM, Moein MR, Kobarfard F, Nasim S, Choudhary MI. 1-D and 2D-NMR assignments of nigricin from Iris imbricate . Iran J Pharm Sci 2005; 4: 250-254
- 28 Zhou J, Xie G, Yan X. Encyclopedia of Traditional Chinese Medicines. Vol. 3. Berlin, Heidelberg, New York: Springer; 2011
- 29 Qiu QH, Zhang ZG, Wang JH, Lv TS. [Studies on the isoflavonoids of Iris tectorum]. Zhong Yao Cai 2009; 32: 1392-1394 [Article in Chinese]
- 30 Kovalev VN, Zatylʼnikova OA, Kovalev SV. A new isoflavone from Iris pseudacorus . Chem Nat Comp 2013; 49: 34-35
- 31 Hsieh CF, Lo C, Liu CH, Lin S, Yen HR, Lin TY, Horng JT. Mechanism by which ma-xing-shi-gan-tang inhibits the entry of influenza virus. J Ethnopharmacol 2012; 143: 57-67
- 32 Jeong HJ, Ryu YB, Park SJ, Kim JH, Kwon HJ, Kim JH, Park KH, Rho MC, Lee WS. Neuraminidase inhibitory activities of flavonols isolated from Rhodiola rosea roots and their in vitro anti-influenza viral activities. Bioorg Med Chem 2009; 17: 6816-6823
- 33 Liu AL, Liu B, Qin HL, Lee SM, Wang YT, Du GH. Anti-influenza virus activities of flavonoids from the medicinal plant Elsholtzia rugulosa . Planta Med 2008; 74: 847-851
- 34 Alhazmi MI. Molecular docking of selected phytocompounds with H1N1 Proteins. Bioinformation 2015; 11: 196-202
- 35 Mehta P, Shah R, Lohidasan S, Mahadik KR. Pharmacokinetic profile of phytoconstituent(s) isolated from medicinal plants-A comprehensive review. J Tradit Complement Med 2015; 5: 207-227
- 36 Hsieh CF, Chen YL, Lin CF, Ho JY, Huang CH, Chiu CH, Horng JT. An extract from Taxodium distichum targets hemagglutinin- and neuraminidase-related activities of influenza virus in vitro . Sci Rep 2016; 6: 1-13
- 37 Sadati S, Gheibi N, Ranjbar S, Hashemzadeh M. Docking study of flavonoid derivatives as potent inhibitors of influenza H1N1 virus neuraminidase. Biomed Rep 2018; 10: 33-38
- 38 Liu Z, Zhao J, Li W, Wang X, Xu J, Xie J, Tao K, Shen L, Zhang R. Molecular docking of potential inhibitors for influenza H7N9. Comput Math Methods Med 2015; 2015: 480764
- 39 Sethy B, Hsieh CF, Yeh C, Horng JT, Hsieh PW. Design, synthesis & structure-activity relationships of a new class of antihuman enterovirus D68 & A71 agents. Future Med Chem 2018; 10: 1333-1347
- 40 Dai W, Bi J, Li F, Wang S, Huang X, Meng X, Sun B, Wang D, Kong W, Jiang C, Su W. Antiviral efficacy of flavonoids against enterovirus 71 infection in vitro and in newborn mice. Viruses 2019; 11: 625
- 41 Zumla A, Chan JF, Azhar EI, Hui DS, Yuen KY. Coronaviruses – drug discovery and therapeutic options. Nat Rev Drug Discov 2016; 15: 327-347
- 42 Rosen J, Lovgren A, Kogej T, Muresan S, Gottfries J, Backlund A. ChemGPS-NP(Web): chemical space navigation online. J Comput Aided Mol Des 2009; 23: 253-259
- 43 Amarelle L, Lecuona E, Sznajder JI. Anti-influenza treatment: Drugs currently used and under development. Arch Bronconeumol 2017; 53: 19-26
- 44 Hu Y, Musharrafieh R, Zheng M, Wang J. Enterovirus D68 antivirals: Past, present, and future. ACS Infect Dis 2020; 6: 1572-1586
- 45 Hsu JTA, Yeh JY, Lin TJ, Li ML, Wu MS, Hsieh CF, Chou YC, Tang WF, Lau KS, Hung HC, Fang MY, Ko S, Hsieh HP, Horng JT. Identification of BPR3P0128 as an inhibitor of cap-snatching activities of influenza virus. Antimicrob Agents Chemother 2012; 56: 647-657
- 46 Hsieh CF, Jheng JR, Lin GH, Chen YL, Ho JY, Liu CJ, Hsu KY, Chen YS, Chan YF, Yu HM, Hsieh PW, Chern JH, Horng JT. Rosmarinic acid exhibits broad anti-enterovirus A71 activity by inhibiting the interaction between the five-fold axis of capsid VP1 and cognate sulfated receptors. Emerg Microbes Infect 2020; 9: 1194-1205
- 47 Boyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl 1968; 97: 77-89
- 48 Korinek M, Hsieh PS, Chen YL, Hsieh PW, Chang SH, Wu YH, Hwang TL. Randialic acid B and tomentosolic acid block formyl peptide receptor 1 in human neutrophils and attenuate psoriasis-like inflammation in vivo . Biochem Pharmacol 2021; 190: 114596
- 49 Yang SC, Chung PJ, Ho CM, Kuo CY, Hung MF, Huang YT, Chang WY, Chang YW, Chan KH, Hwang TL. Propofol inhibits superoxide production, elastase release, and chemotaxis in formyl peptide-activated human neutrophils by blocking formyl peptide receptor 1. J Immunol 2013; 190: 6511-6519
- 50 Hwang TL, Su YC, Chang HL, Leu YL, Chung PJ, Kuo LM, Chang YJ. Suppression of superoxide anion and elastase release by C18 unsaturated fatty acids in human neutrophils. J Lipid Res 2009; 50: 1395-1408