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DOI: 10.1055/a-1345-6831
Inactivation of Herpes Simplex Virus by Photosensitizing Anthraquinones Isolated from Heterophyllaea pustulata
Gefördert durch: Consejo Nacional de Ciencia y Tecnología de Argentina (CONICET) PIP-2013-2015, res. GI 4316/2013Gefördert durch: Fondo para la Investigación Científica y Tecnológica (FONCYT) BID-PICT 2014 n° 2204, res. ANPCyT n° 270/25
Gefördert durch: Fondo para la Investigación Científica y Tecnológica (FONCYT) BID-PICT 2016 Nº 1697, res. ANPCyT n° 285/17
Gefördert durch: Secretaria de Ciencia y Tecnología, Universidad Nacional de Córdoba (SeCyT-UNC) Proyecto Consolidar 2018-2021, res. N° 411/18, 99
Gefördert durch: Secretaria de Ciencia y Tecnología, Universidad Nacional de Córdoba (SeCyT-UNC) Proyecto “FORMAR”, res. N° 411/18, 99/19
Gefördert durch: Secretaria de Ciencia y Tecnología, Universidad Nacional de Córdoba (SeCyT-UNC) SeCyT 2016-2017, res. n° 366/16 y 113/17
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Abstract
Heterophyllaea pustulata is a phototoxic plant from Argentina. Aerial parts extracts, high in photosensitizing anthraquinones, have shown in vitro antiviral activity. The purpose of this study was to study the antiherpetic activity of the main purified anthraquinones, even evaluating their competence as photodynamic sensitizers to photo-stimulate the antiviral effect. In vitro antiviral activity against Herpes Simplex virus type I and the photo-inactivation of viral particle were studied by the Neutral Red uptake test and observation of the cytopathic effect. Rubiadin 1-methyl ether and 5,5′-bisoranjidiol produced a significant effect (≥ 80% inhibition) with minimal damage to host cells (subtoxic concentration). Anthraquinones with poor antiherpetic activity at its maximum noncytotoxic concentration showed an important photo-stimulated effect, such is the case of soranjidiol and 5,5′-bisoranjidiol (28.0 ± 6.3 vs. 81.8 ± 2.1% and 15.5 ± 0.3 vs. 89.8 ± 1.7%, respectively). The study also proved the decrease of viral particles, necessary to reduce infection. Therefore, photosensitizing anthraquinones from natural resources could be proposed to develop new treatments for localized viral lesions with antimicrobial photodynamic therapy.
Key words
Heterophyllaea pustulata - Rubiaceae - anthraquinones - Herpes Simplex virus type I - photo-inactivation - antiviral activity - antimicrobial photodynamic therapySupporting Information
- Supporting Information
As supporting information, we included the spectral data of each tested AQ, the HPLC chromatograms showing their purity, and the emission spectrum of the lamp used in the irradiation system.
Publikationsverlauf
Eingereicht: 25. September 2020
Angenommen nach Revision: 04. Januar 2021
Artikel online veröffentlicht:
23. Februar 2021
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References
- 1 Bacigalupo NM. Rubiaceae. In: Cabrera AL. ed. Flora de la Provincia de Jujuy. Buenos Aires: INTA; 1993: 375-380
- 2 Hansen EW, Martiarena CA. Contribución al estudio de toxicidad de Heterophyllaea pustulata Hook “cegadera” en el ganado. Rev Invest Agrop (INTA) 1967; 4: 81-113
- 3 Núñez Montoya SC, Agnese AM, Cabrera JL. Anthraquinone derivatives from Heterophyllaea pustulata . J Nat Prod 2006; 69: 801-803 doi:10.1021/np050181o
- 4 Comini LR, Núñez Montoya SC, Sarmiento M, Cabrera JL, Argüello GA. Characterizing some photophysical, photochemical and photobiological properties of photosensitizing anthraquinones. J Photochem Photobiol A Chem 2007; 188: 185-191 doi:10.1016/j.jphotochem.2006.12.011
- 5 Marioni J, Arce JE, Cabrera JL, Paraje MG, Núñez Montoya SC. Reduction of Candida tropicalis biofilm by photoactivation of a Heterophyllaea pustulata extract. Pharm Biol 2016; 54: 2791-2801 doi:10.1080/13880209.2016.1183683
- 6 Konigheim BS, Beranek M, Comini LR, Aguilar JJ, Marioni J, Cabrera JL, Núñez Montoya SC. In vitro antiviral activity of Heterophyllaea pustulata extracts. Nat Prod Commun 2012; 7: 1025-1028 doi:10.1177/1934578X1200700816
- 7 Comini LR, Núñez Montoya SC, Páez PL, Argüello GA, Albesa I, Cabrera JL. Antibacterial activity of anthraquinone derivatives from Heterophyllaea pustulata (Rubiaceae). J Photochem Photobiol B Biol 2011; 102: 108-114 doi:10.1016/j.jphotobiol.2010.09.009
- 8 Comini LR, Fernandez IM, Rumie Vittar NB, Núñez Montoya SC, Cabrera JL, Rivarola VA. Photodynamic activity of anthraquinones isolated from Heterophyllaea pustulata Hook f. (Rubiaceae) on MCF-7c3 breast cancer cells. Phytomedicine 2011; 18: 1093-1095 doi:10.1016/j.phymed.2011.05.008
- 9 Marioni J, Bresolí-Obach R, Agut M, Comini LR, Cabrera JL, Paraje MG, Núñez Montoya SC. On the mechanism of Candida tropicalis biofilm reduction by the combined action of naturally-occurring anthraquinones and blue light. PLoS One 2017; 12: e0181517 doi:10.1371/journal.pone.0181517
- 10 Fatahzadeh M, Schwartz RA. Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management. J Am Acad Dermatol 2007; 57: 737-763 doi:10.1016/j.jaad.2007.06.027
- 11 Yan C, Luo Z, Li W, Li X, Dallmann R, Kurihara H, He RR. Disturbed Yin-Yang balance: stress increases the susceptibility to herpes simplex virus type 1 primary and recurrent infections. Acta Pharmaceutica Sinica B 2020; 10: 383-398 doi:10.1016/j.apsb.2019.06.005
- 12 Álvarez DM, Castillo E, Duarte LF, Arriagada J, Corrales N, Farías MA, Henríquez A, Agurto-Muñoz C, González PA. Current antivirals and novel botanical molecules interfering with herpes simplex virus infection. Front Microbiol 2020; 11: 139 doi:10.3389/fmicb.2020.00139
- 13 Hamblin MR. Antimicrobial photodynamic inactivation: a bright new technique to kill resistant microbes. Curr Opin Microbiol 2016; 33: 67-73 doi:10.1016/j.mib.2016.06.008
- 14 Siewert B, Stuppner H. The photoactivity of natural products–an overlooked potential of phytomedicines. Phytomedicine 2019; 60: 152985 doi:10.1016/j.phymed.2019.152985
- 15 Del Barrio Alonso G, Alvarez Rodriguez ÁL, Valdes Garcia SM, Parra Fernandez F. Metodología de pesquisa preclínica de actividad anti-herpesvirus a partir de productos naturales. Rev Cubana Farm 2008; 42: 0 Accessed online April 06, 2020 at: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S0034-75152008000200008
- 16 Wijnsma R, Verpoorte R. Anthraquinones in the Rubiaceae. In: Grisebach H, Kirby G, Tamm Ch. eds. Progress in the Chemistry of organic natural Products. Wien: Springer; 1986: 79-149
- 17 Alves DS, Pérez-Fons L, Estepa A, Micol V. Membrane-related effects underlying the biological activity of the anthraquinones emodin and barbaloin. Biochem Pharmacol 2004; 68: 549-561 doi:10.1016/j.bcp.2004.04.012
- 18 Battistutta R, Sarno S, De Moliner E, Papinutto E, Zanotti G, Pinna LA. The replacement of ATP by the competitive inhibitor emodin induces conformational modifications in the catalytic site of protein kinase CK2. J Biol Chem 2000; 275: 29618-29622
- 19 Yim H, Lee YH, Lee CH, Lee SK. Emodin, an anthraquinone derivative isolated from the rhizomes of Rheum palmatum, selectively inhibits the activity of casein kinase II as a competitive inhibitor. Planta Med 1999; 65: 9-13
- 20 Hsiang CY, Ho TY. Emodin is a novel alkaline nuclease inhibitor that suppresses herpes simplex virus type 1 yields in cell cultures. Br J Pharmacol 2008; 155: 227-235
- 21 Hassan ST, Masarčíková R, Berchová K. Bioactive natural products with anti‐herpes simplex virus properties. J Pharm Pharmacol 2015; 67: 1325-1336 doi:10.1111/jphp.12436
- 22 Knipe D, Howley P. Herpes simplex Viruses. In: Knipe D, Howley P. eds. Fields Virology. 5th ed. Boston: Lippincott Williams y Wilkins; 2007: 2515
- 23 Tomé JP, Silva EM, Pereira AM, Alonso CM, Faustino MA, Neves MG, Valdeira ML. Synthesis of neutral and cationic tripyridylporphyrin-D-galactose conjugates and the photoinactivation of HSV-1. Bioorg Med Chem 2007; 15: 4705-4713
- 24 Latief MA, Chikama T, Ko JA, Kiuchi Y, Sakaguchi T, Obana A. Inactivation of acyclovir-sensitive and-resistant strains of herpes simplex virus type 1 in vitro by photodynamic antimicrobial chemotherapy. Mol Vis 2015; 21: 532-537 Accessed September 2, 2020 at: http://www.molvis.org/molvis/v21/532
- 25 Contigiani MS, Sabattini MS. Virulencia diferencial de cepas de virus Junín por marcadores biológicos en ratones y cobayos. Medicina 1977; 37: 244-251
- 26 Konigheim BS, Comini LR, Grasso S, Aguilar JJ, Marioni J, Contigiani MS, Núñez Montoya SC. Determination of non-toxic and subtoxic concentrations of potential antiviral natural anthraquinones. Lat Am J Pharm 2012; 31: 51-56
- 27 Borenfreund E, Puerner JA. Toxicity determined in vitro by morphological alterations and neutral red absorption. Toxicol Lett 1985; 24: 119-124 doi:10.1016/0378-4274(85)90046-3
- 28 Gescher K, Kühn J, Hafezi W, Louis A, Derksen A, Deters A, Hensel A. Inhibition of viral adsorption and penetration by an aqueous extract from Rhododendron ferrugineum L. as antiviral principle against herpes simplex virus type-1. Fitoterapia 2011; 82: 408-413 doi:10.1016/j.fitote.2010.11.022
- 29 Phototherapy lamps Philips, in catalogue on line. Accessed September 2, 2020 at: http://www.philips.com/phototherapy