Alpinone exhibited immunomodulatory and antiviral activities in Atlantic salmon

B. Valenzuela, F.E. Rodríguez, B. Modak, M. Imarai

Research output: Contribution to journalArticle

Abstract

In this study, we seek to identify flavonoids able to regulate the gene expression of a group of cytokines important for the control of infections in Atlantic salmon (Salmo salar). Particularly, we studied the potential immunomodulatory effects of two flavonoids, Alpinone and Pinocembrine, which were isolated and purified from resinous exudates of Heliotropium huascoense and Heliotropium sinuatum, respectively. The transcript levels of TNF-α and IL-1 (inflammatory cytokines), IFN-γ and IL-12 (T helper 1 type cytokines), IL4/13A (Th2-type cytokine), IL-17 (Th17 type cytokine) TGF-β1 (regulatory cytokine) and IFN-α (antiviral cytokine) were quantified by qRT-PCR in kidneys of flavonoid-treated and control fish. We demonstrated that the administration of a single intramuscular dose of purified Alpinone increased the transcriptional expression of five cytokines, named TNF-α, IL-1, IFN-α, IFN-γ and TGF-β1 in treated fish compared to untreated fish. Conversely, administration of purified Pinocembrine reduced the transcriptional expression of TNF-α, IL-1 and IL-12 in the kidney of treated fish. No other changes were observed. Interestingly, Alpinone also induced in vitro antiviral effects against Infectious Salmon Anaemia virus. Results showed that Alpinone but not Pinocembrine induces the expression of cytokines, which in vertebrates are essential to control viral infections while Pinocembrine reduces pro-inflammatory cytokines. Altogether results suggest that Alpinone is a good candidate to be further tested as immunostimulant and antiviral drug. © 2017 Elsevier Ltd
LanguageEnglish
Pages76-83
Number of pages8
JournalFish and Shellfish Immunology
Volume74
DOIs
Publication statusPublished - 2018

Fingerprint

Salmo salar
Antiviral Agents
cytokines
Cytokines
fish
Fish
interleukin-1
Interleukin-1
anemia
Flavonoids
Heliotropium
tumor necrosis factor-alpha
flavonoids
Tumor Necrosis Factor-alpha
gene expression
interleukin-12
Interleukin-12
virus
vertebrate
drug

Keywords

  • Alpinone
  • Anti-inflammatory
  • Antiviral activity
  • Atlantic salmon
  • Cytokines
  • Flavonoids
  • IFN alpha
  • Immunostimulant
  • ISAV
  • Pinocembrine
  • Teleost fish
  • Th1-type response
  • alpinone
  • antivirus agent
  • flavonoid
  • gamma interferon
  • immunomodulating agent
  • interleukin 1
  • interleukin 12
  • interleukin 13
  • interleukin 13a
  • interleukin 17
  • interleukin 4
  • pinocembrine
  • transforming growth factor beta1
  • tumor necrosis factor
  • unclassified drug
  • antiviral activity
  • Article
  • controlled study
  • gene expression
  • Heliotropium
  • Heliotropium huascoense
  • Heliotropium sinuatum
  • infectious salmon anemia
  • infectious salmon anemia virus
  • nonhuman
  • priority journal
  • reverse transcription polymerase chain reaction
  • Salmo salar
  • SHK-1 cell line

Cite this

Alpinone exhibited immunomodulatory and antiviral activities in Atlantic salmon. / Valenzuela, B.; Rodríguez, F.E.; Modak, B.; Imarai, M.

In: Fish and Shellfish Immunology, Vol. 74, 2018, p. 76-83.

Research output: Contribution to journalArticle

Valenzuela, B. ; Rodríguez, F.E. ; Modak, B. ; Imarai, M. / Alpinone exhibited immunomodulatory and antiviral activities in Atlantic salmon. In: Fish and Shellfish Immunology. 2018 ; Vol. 74. pp. 76-83.
@article{d56095c8f4e04b31a72a406574d8b94f,
title = "Alpinone exhibited immunomodulatory and antiviral activities in Atlantic salmon",
abstract = "In this study, we seek to identify flavonoids able to regulate the gene expression of a group of cytokines important for the control of infections in Atlantic salmon (Salmo salar). Particularly, we studied the potential immunomodulatory effects of two flavonoids, Alpinone and Pinocembrine, which were isolated and purified from resinous exudates of Heliotropium huascoense and Heliotropium sinuatum, respectively. The transcript levels of TNF-α and IL-1 (inflammatory cytokines), IFN-γ and IL-12 (T helper 1 type cytokines), IL4/13A (Th2-type cytokine), IL-17 (Th17 type cytokine) TGF-β1 (regulatory cytokine) and IFN-α (antiviral cytokine) were quantified by qRT-PCR in kidneys of flavonoid-treated and control fish. We demonstrated that the administration of a single intramuscular dose of purified Alpinone increased the transcriptional expression of five cytokines, named TNF-α, IL-1, IFN-α, IFN-γ and TGF-β1 in treated fish compared to untreated fish. Conversely, administration of purified Pinocembrine reduced the transcriptional expression of TNF-α, IL-1 and IL-12 in the kidney of treated fish. No other changes were observed. Interestingly, Alpinone also induced in vitro antiviral effects against Infectious Salmon Anaemia virus. Results showed that Alpinone but not Pinocembrine induces the expression of cytokines, which in vertebrates are essential to control viral infections while Pinocembrine reduces pro-inflammatory cytokines. Altogether results suggest that Alpinone is a good candidate to be further tested as immunostimulant and antiviral drug. {\circledC} 2017 Elsevier Ltd",
keywords = "Alpinone, Anti-inflammatory, Antiviral activity, Atlantic salmon, Cytokines, Flavonoids, IFN alpha, Immunostimulant, ISAV, Pinocembrine, Teleost fish, Th1-type response, alpinone, antivirus agent, flavonoid, gamma interferon, immunomodulating agent, interleukin 1, interleukin 12, interleukin 13, interleukin 13a, interleukin 17, interleukin 4, pinocembrine, transforming growth factor beta1, tumor necrosis factor, unclassified drug, antiviral activity, Article, controlled study, gene expression, Heliotropium, Heliotropium huascoense, Heliotropium sinuatum, infectious salmon anemia, infectious salmon anemia virus, nonhuman, priority journal, reverse transcription polymerase chain reaction, Salmo salar, SHK-1 cell line",
author = "B. Valenzuela and F.E. Rodr{\'i}guez and B. Modak and M. Imarai",
note = "Export Date: 12 April 2018 CODEN: FSIME Correspondence Address: Imarai, M.; Laboratory of Immunology, Center of Aquatic Biotechnology, Department of Biology, Faculty of Chemistry and Biology, University of Santiago of Chile, Av. Bernardo O'Higgins, Chile; email: monica.imarai@usach.cl Chemicals/CAS: gamma interferon, 82115-62-6; interleukin 12, 138415-13-1; interleukin 13, 148157-34-0; pinocembrine, 480-39-7 Funding details: 1140261, FONDECYT, Fondo Nacional de Desarrollo Cient{\'i}fico y Tecnol{\'o}gico Funding details: 1161015, FONDECYT, Fondo Nacional de Desarrollo Cient{\'i}fico y Tecnol{\'o}gico Funding text: FONDECYT1140261 and 1161015, Basal USA 1555, Basal USA 1298, Basal USA 1498 financed this work. We also thank Carolina Espinoza and Carolina Camus for outstanding technical assistance. References: Crane, M., Hyatt, A., Viruses of fish: an overview of significant pathogens (2011) Viruses, 3 (11), pp. 2025-2046; Gomez-Casado, E., Estepa, A., Coll, J.M., A comparative review on European-farmed finfish RNA viruses and their vaccines (2011) Vaccine, 29 (15), pp. 2657-2671; Kang, S.Y., Kang, J.Y., Oh, M.J., Antiviral activities of flavonoids isolated from the bark of Rhus verniciflua stokes against fish pathogenic viruses in Vitro (2012) J. Microbiol., 50 (2), pp. 293-300; Martinez, J.P., Sasse, F., Bronstrup, M., Diez, J., Meyerhans, A., Antiviral drug discovery: broad-spectrum drugs from nature (2015) Nat. Prod. Rep., 32 (1), pp. 29-48; Chandra, H., Bishnoi, P., Yadav, A., Patni, B., Mishra, A.P., Nautiyal, A.R., Antimicrobial resistance and the alternative resources with special emphasis on plant-based antimicrobials-a review (2017) Plants, 6 (2). , (Basel); Naithani, R., Huma, L.C., Holland, L.E., Shukla, D., McCormick, D.L., Mehta, R.G., Moriarty, R.M., Antiviral activity of phytochemicals: a comprehensive review (2008) Mini Rev. Med. Chem., 8 (11), pp. 1106-1133; Luebert, F., A revision of Heliotropium sect. Cochranea (Heliotropiaceae) (2013) Kew Bull., 68, pp. 1-54; Modak, B., Rojas, M., Torres, R., Rodilla, J., Luebert, F., Antioxidant activity of a new aromatic geranyl derivative of the resinous exudates from Heliotropium glutinosum Phil (2007) Molecules, 12 (5), pp. 1057-1063; Modak, B., Salina, M., Rodilla, J., Torres, R., Study of the chemical composition of the resinous exudate isolated from Heliotropium sclerocarpum and evaluation of the antioxidant properties of the phenolic compounds and the resin (2009) Molecules, 14 (11), pp. 4625-4633; Modak, B., Torres, R., Lissi, E., delle Monache, F., Antioxidant capacity of flavonoids and a new arylphenol of the resinous exudate from Heliotropium sinuatum (2003) Nat. Prod. Res., 17 (6), pp. 403-407; Torres, R., Modak, B., Urzua, A., Villarroel, L., Delle Monache, F., Sanchez-Ferrando, F., Flavonoides del exudado resinoso de Heliotropium sinuatum (1996) Bol. Soc. Chil. Quim., 41, pp. 195-197; Modak, B., Contreras, M.L., Gonzalez-Nilo, F., Torres, R., Structure-antioxidant activity relationships of flavonoids isolated from the resinous exudate of Heliotropium sinuatum (2005) Bioorg. Med. Chem. Lett, 15 (2), pp. 309-312; Modak, B., Rojas, M., Torres, R., Chemical analysis of the resinous exudate isolated from Heliotropium taltalense and evaluation of the antioxidant activity of the phenolics components and the resin in homogeneous and heterogeneous systems (2009) Molecules, 14 (6), pp. 1980-1989; Modak, B., Sandino, A.M., Arata, L., Cardenas-Jiron, G., Torres, R., Inhibitory effect of aromatic geranyl derivatives isolated from Heliotropium filifolium on infectious pancreatic necrosis virus replication (2010) Vet. Microbiol., 141 (1-2), pp. 53-58; Urzua, A., Modak, A., Villarroel, L., Torres, R., Andrade, L., Mendoza, L., Wilkens, M., External flavonoids fro Heliotropium magalanthum and huescoense (Boraginavceae). Chemotaxonomic considerations (2000) Bol. Soc. Chil. Quim., 45 (1); Valenzuela, B., Imarai, M., Catalan, R., Parra, M., Soto, S., Sandino, A., Torres, R., Modak, B., Evaluation of the bactericidal activity of secondary metabolites isolated from Heliotropium genus against Piscirickettsia salmonis (2015) Bol. Latinoam. Caribe Plantas Med. Aromat. (BLACPMA), 14 (2), pp. 131-140; Modak, B., Rivas, A., Vallejos, E., Sandino, A., Spencer, E., Antiviral activity in vitro and in vivo of natural flavonoids isolated from Heliotropium sinuatum against infectious salmon anemia virus (ISAV) (2012) Bol. Latinoam. Caribe Plantas Med. Aromat. (BLACPMA), 11 (4), pp. 377-384; Modak, B., Torres, R., Wilkens, M., Urzua, A., Antibacterial activity of compounds isolated of the resinous exudates from Heliotropium sinuatum of phytopathogenic bacteria (2004) J. Chil. Chem. Soc., 49, pp. 1-3; Valenzuela, B., Imarai, M., Torres, R., Modak, B., Immunomodulatory effects of the aromatic geranyl derivative filifolinone tested by the induction of cytokine expression (2013) Dev. Comp. Immunol., 41 (4), pp. 675-682; Kumar, S., Pandey, A.K., Chemistry and biological activities of flavonoids: an overview (2013) Sci. Tech. Rep., 2013, p. 162750; Modak, B., Arrieta, A., Torres, R., Urz{\'u}a, A., Activated antibacteriana de flavonoides aislados del exudado resinoso de Heliotropium sinuatum: efecto del tipo de estructura (2002) J. Chil. Chem. Soc., 47, pp. 19-23; Han, M.S., Lee, I.K., Kim, Y.S., Kim, J.H., Kim, J.T., Shoe, K.R., Yun, B.S., Flavonoids from propolis inhibit DNA single strand breakage by the fenton reaction (2010) J. Kor. Soc. Appl. Biol. Chem., 53, pp. 512-515; Chabalgoity, J.A., Baz, A., Rial, A., Grille, S., The relevance of cytokines for development of protective immunity and rational design of vaccines (2007) Cytokine Growth Factor Rev., 18 (1-2), pp. 195-207; Zou, J., Secombes, C.J., The function of fish cytokines (2016) Biology, 5 (2). , (Basel); Svingerud, T., Solstad, T., Sun, B., Nyrud, M.L., Kileng, O., Greiner-Tollersrud, L., Robertsen, B., Atlantic salmon type I IFN subtypes show differences in antiviral activity and cell-dependent expression: evidence for high IFNb/IFNc-producing cells in fish lymphoid tissues (2012) J. Immunol., 189 (12), pp. 5912-5923; Chang, C.J., Robertsen, C., Sun, B., Robertsen, B., Protection of Atlantic salmon against virus infection by intramuscular injection of IFNc expression plasmid (2014) Vaccine, 32 (36), pp. 4695-4702; Zou, J., Carrington, A., Collet, B., Dijkstra, J.M., Yoshiura, Y., Bols, N., Secombes, C., Identification and bioactivities of IFN-gamma in rainbow trout Oncorhynchus mykiss: the first Th1-type cytokine characterized functionally in fish (2005) J. Immunol., 175 (4), pp. 2484-2494; Dannevig, B.H., Falk, K., Namork, E., Isolation of the causal virus of infectious salmon anaemia (ISA) in a long-term cell line from Atlantic salmon head kidney (1995) J. Gen. Virol., 76, pp. 1353-1359; Devold, M., Krossoy, B., Aspehaug, V., Nylund, A., Use of RT-PCR for diagnosis of infectious salmon anaemia virus (ISAV) in carrier sea trout Salmo trutta after experimental infection (2000) Dis. Aquat. Org., 40 (1), pp. 9-18; Cottet, L., Rivas-Aravena, A., Cortez-San Martin, M., Sandino, A.M., Spencer, E., Infectious salmon anemia virus–genetics and pathogenesis (2011) Virus Res., 155 (1), pp. 10-19; Munir, K., Kibenge, F.S., Detection of infectious salmon anaemia virus by real-time RT-PCR (2004) J. Virol Meth., 117 (1), pp. 37-47; Reyes-Cerpa, S., Reyes-Lopez, F.E., Toro-Ascuy, D., Ibanez, J., Maisey, K., Sandino, A.M., Imarai, M., IPNV modulation of pro and anti-inflammatory cytokine expression in Atlantic salmon might help the establishment of infection and persistence (2012) Fish Shellfish Immunol., 32 (2), pp. 291-300; Wang, T., Husain, M., Hong, S., Holland, J.W., Differential expression, modulation and bioactivity of distinct fish IL-12 isoforms: implication towards the evolution of Th1-like immune responses (2014) Eur. J. 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Immunol., 32, pp. 51-82; Robertsen, B., The role of type I interferons in innate and adaptive immunity against viruses in Atlantic salmon (2018) Dev. Comp. Immunol., 80, pp. 41-52; Chang, C.J., Sun, B., Robertsen, B., Adjuvant activity of fish type I interferon shown in a virus DNA vaccination model (2015) Vaccine, 33 (21), pp. 2442-2448; Wong, G.H., Goeddel, D.V., Tumour necrosis factors alpha and beta inhibit virus replication and synergize with interferons (1986) Nature, 323 (6091), pp. 819-822; Mestan, J., Digel, W., Mittnacht, S., Hillen, H., Blohm, D., Moller, A., Jacobsen, H., Kirchner, H., Antiviral effects of recombinant tumour necrosis factor in vitro (1986) Nature, 323 (6091), pp. 816-819; Kakegawa, T., Miyazaki, A., Yasukawa, K., Anti-inflammatory effects of alpinone 3-acetate from Alpinia japonica seeds (2016) J. Nat. 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year = "2018",
doi = "10.1016/j.fsi.2017.12.043",
language = "English",
volume = "74",
pages = "76--83",
journal = "Fish and Shellfish Immunology",
issn = "1050-4648",
publisher = "Caister Academic Press",

}

TY - JOUR

T1 - Alpinone exhibited immunomodulatory and antiviral activities in Atlantic salmon

AU - Valenzuela, B.

AU - Rodríguez, F.E.

AU - Modak, B.

AU - Imarai, M.

N1 - Export Date: 12 April 2018 CODEN: FSIME Correspondence Address: Imarai, M.; Laboratory of Immunology, Center of Aquatic Biotechnology, Department of Biology, Faculty of Chemistry and Biology, University of Santiago of Chile, Av. Bernardo O'Higgins, Chile; email: monica.imarai@usach.cl Chemicals/CAS: gamma interferon, 82115-62-6; interleukin 12, 138415-13-1; interleukin 13, 148157-34-0; pinocembrine, 480-39-7 Funding details: 1140261, FONDECYT, Fondo Nacional de Desarrollo Científico y Tecnológico Funding details: 1161015, FONDECYT, Fondo Nacional de Desarrollo Científico y Tecnológico Funding text: FONDECYT1140261 and 1161015, Basal USA 1555, Basal USA 1298, Basal USA 1498 financed this work. We also thank Carolina Espinoza and Carolina Camus for outstanding technical assistance. References: Crane, M., Hyatt, A., Viruses of fish: an overview of significant pathogens (2011) Viruses, 3 (11), pp. 2025-2046; Gomez-Casado, E., Estepa, A., Coll, J.M., A comparative review on European-farmed finfish RNA viruses and their vaccines (2011) Vaccine, 29 (15), pp. 2657-2671; Kang, S.Y., Kang, J.Y., Oh, M.J., Antiviral activities of flavonoids isolated from the bark of Rhus verniciflua stokes against fish pathogenic viruses in Vitro (2012) J. Microbiol., 50 (2), pp. 293-300; Martinez, J.P., Sasse, F., Bronstrup, M., Diez, J., Meyerhans, A., Antiviral drug discovery: broad-spectrum drugs from nature (2015) Nat. Prod. Rep., 32 (1), pp. 29-48; Chandra, H., Bishnoi, P., Yadav, A., Patni, B., Mishra, A.P., Nautiyal, A.R., Antimicrobial resistance and the alternative resources with special emphasis on plant-based antimicrobials-a review (2017) Plants, 6 (2). , (Basel); Naithani, R., Huma, L.C., Holland, L.E., Shukla, D., McCormick, D.L., Mehta, R.G., Moriarty, R.M., Antiviral activity of phytochemicals: a comprehensive review (2008) Mini Rev. Med. Chem., 8 (11), pp. 1106-1133; Luebert, F., A revision of Heliotropium sect. Cochranea (Heliotropiaceae) (2013) Kew Bull., 68, pp. 1-54; Modak, B., Rojas, M., Torres, R., Rodilla, J., Luebert, F., Antioxidant activity of a new aromatic geranyl derivative of the resinous exudates from Heliotropium glutinosum Phil (2007) Molecules, 12 (5), pp. 1057-1063; Modak, B., Salina, M., Rodilla, J., Torres, R., Study of the chemical composition of the resinous exudate isolated from Heliotropium sclerocarpum and evaluation of the antioxidant properties of the phenolic compounds and the resin (2009) Molecules, 14 (11), pp. 4625-4633; Modak, B., Torres, R., Lissi, E., delle Monache, F., Antioxidant capacity of flavonoids and a new arylphenol of the resinous exudate from Heliotropium sinuatum (2003) Nat. Prod. Res., 17 (6), pp. 403-407; Torres, R., Modak, B., Urzua, A., Villarroel, L., Delle Monache, F., Sanchez-Ferrando, F., Flavonoides del exudado resinoso de Heliotropium sinuatum (1996) Bol. Soc. Chil. Quim., 41, pp. 195-197; Modak, B., Contreras, M.L., Gonzalez-Nilo, F., Torres, R., Structure-antioxidant activity relationships of flavonoids isolated from the resinous exudate of Heliotropium sinuatum (2005) Bioorg. Med. Chem. Lett, 15 (2), pp. 309-312; Modak, B., Rojas, M., Torres, R., Chemical analysis of the resinous exudate isolated from Heliotropium taltalense and evaluation of the antioxidant activity of the phenolics components and the resin in homogeneous and heterogeneous systems (2009) Molecules, 14 (6), pp. 1980-1989; Modak, B., Sandino, A.M., Arata, L., Cardenas-Jiron, G., Torres, R., Inhibitory effect of aromatic geranyl derivatives isolated from Heliotropium filifolium on infectious pancreatic necrosis virus replication (2010) Vet. Microbiol., 141 (1-2), pp. 53-58; Urzua, A., Modak, A., Villarroel, L., Torres, R., Andrade, L., Mendoza, L., Wilkens, M., External flavonoids fro Heliotropium magalanthum and huescoense (Boraginavceae). Chemotaxonomic considerations (2000) Bol. Soc. Chil. Quim., 45 (1); Valenzuela, B., Imarai, M., Catalan, R., Parra, M., Soto, S., Sandino, A., Torres, R., Modak, B., Evaluation of the bactericidal activity of secondary metabolites isolated from Heliotropium genus against Piscirickettsia salmonis (2015) Bol. Latinoam. Caribe Plantas Med. Aromat. (BLACPMA), 14 (2), pp. 131-140; Modak, B., Rivas, A., Vallejos, E., Sandino, A., Spencer, E., Antiviral activity in vitro and in vivo of natural flavonoids isolated from Heliotropium sinuatum against infectious salmon anemia virus (ISAV) (2012) Bol. Latinoam. Caribe Plantas Med. Aromat. (BLACPMA), 11 (4), pp. 377-384; Modak, B., Torres, R., Wilkens, M., Urzua, A., Antibacterial activity of compounds isolated of the resinous exudates from Heliotropium sinuatum of phytopathogenic bacteria (2004) J. Chil. Chem. Soc., 49, pp. 1-3; Valenzuela, B., Imarai, M., Torres, R., Modak, B., Immunomodulatory effects of the aromatic geranyl derivative filifolinone tested by the induction of cytokine expression (2013) Dev. Comp. Immunol., 41 (4), pp. 675-682; Kumar, S., Pandey, A.K., Chemistry and biological activities of flavonoids: an overview (2013) Sci. Tech. Rep., 2013, p. 162750; Modak, B., Arrieta, A., Torres, R., Urzúa, A., Activated antibacteriana de flavonoides aislados del exudado resinoso de Heliotropium sinuatum: efecto del tipo de estructura (2002) J. Chil. Chem. Soc., 47, pp. 19-23; Han, M.S., Lee, I.K., Kim, Y.S., Kim, J.H., Kim, J.T., Shoe, K.R., Yun, B.S., Flavonoids from propolis inhibit DNA single strand breakage by the fenton reaction (2010) J. Kor. Soc. Appl. Biol. Chem., 53, pp. 512-515; Chabalgoity, J.A., Baz, A., Rial, A., Grille, S., The relevance of cytokines for development of protective immunity and rational design of vaccines (2007) Cytokine Growth Factor Rev., 18 (1-2), pp. 195-207; Zou, J., Secombes, C.J., The function of fish cytokines (2016) Biology, 5 (2). , (Basel); Svingerud, T., Solstad, T., Sun, B., Nyrud, M.L., Kileng, O., Greiner-Tollersrud, L., Robertsen, B., Atlantic salmon type I IFN subtypes show differences in antiviral activity and cell-dependent expression: evidence for high IFNb/IFNc-producing cells in fish lymphoid tissues (2012) J. Immunol., 189 (12), pp. 5912-5923; Chang, C.J., Robertsen, C., Sun, B., Robertsen, B., Protection of Atlantic salmon against virus infection by intramuscular injection of IFNc expression plasmid (2014) Vaccine, 32 (36), pp. 4695-4702; Zou, J., Carrington, A., Collet, B., Dijkstra, J.M., Yoshiura, Y., Bols, N., Secombes, C., Identification and bioactivities of IFN-gamma in rainbow trout Oncorhynchus mykiss: the first Th1-type cytokine characterized functionally in fish (2005) J. Immunol., 175 (4), pp. 2484-2494; Dannevig, B.H., Falk, K., Namork, E., Isolation of the causal virus of infectious salmon anaemia (ISA) in a long-term cell line from Atlantic salmon head kidney (1995) J. Gen. Virol., 76, pp. 1353-1359; Devold, M., Krossoy, B., Aspehaug, V., Nylund, A., Use of RT-PCR for diagnosis of infectious salmon anaemia virus (ISAV) in carrier sea trout Salmo trutta after experimental infection (2000) Dis. Aquat. Org., 40 (1), pp. 9-18; Cottet, L., Rivas-Aravena, A., Cortez-San Martin, M., Sandino, A.M., Spencer, E., Infectious salmon anemia virus–genetics and pathogenesis (2011) Virus Res., 155 (1), pp. 10-19; Munir, K., Kibenge, F.S., Detection of infectious salmon anaemia virus by real-time RT-PCR (2004) J. Virol Meth., 117 (1), pp. 37-47; Reyes-Cerpa, S., Reyes-Lopez, F.E., Toro-Ascuy, D., Ibanez, J., Maisey, K., Sandino, A.M., Imarai, M., IPNV modulation of pro and anti-inflammatory cytokine expression in Atlantic salmon might help the establishment of infection and persistence (2012) Fish Shellfish Immunol., 32 (2), pp. 291-300; Wang, T., Husain, M., Hong, S., Holland, J.W., Differential expression, modulation and bioactivity of distinct fish IL-12 isoforms: implication towards the evolution of Th1-like immune responses (2014) Eur. J. 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PY - 2018

Y1 - 2018

N2 - In this study, we seek to identify flavonoids able to regulate the gene expression of a group of cytokines important for the control of infections in Atlantic salmon (Salmo salar). Particularly, we studied the potential immunomodulatory effects of two flavonoids, Alpinone and Pinocembrine, which were isolated and purified from resinous exudates of Heliotropium huascoense and Heliotropium sinuatum, respectively. The transcript levels of TNF-α and IL-1 (inflammatory cytokines), IFN-γ and IL-12 (T helper 1 type cytokines), IL4/13A (Th2-type cytokine), IL-17 (Th17 type cytokine) TGF-β1 (regulatory cytokine) and IFN-α (antiviral cytokine) were quantified by qRT-PCR in kidneys of flavonoid-treated and control fish. We demonstrated that the administration of a single intramuscular dose of purified Alpinone increased the transcriptional expression of five cytokines, named TNF-α, IL-1, IFN-α, IFN-γ and TGF-β1 in treated fish compared to untreated fish. Conversely, administration of purified Pinocembrine reduced the transcriptional expression of TNF-α, IL-1 and IL-12 in the kidney of treated fish. No other changes were observed. Interestingly, Alpinone also induced in vitro antiviral effects against Infectious Salmon Anaemia virus. Results showed that Alpinone but not Pinocembrine induces the expression of cytokines, which in vertebrates are essential to control viral infections while Pinocembrine reduces pro-inflammatory cytokines. Altogether results suggest that Alpinone is a good candidate to be further tested as immunostimulant and antiviral drug. © 2017 Elsevier Ltd

AB - In this study, we seek to identify flavonoids able to regulate the gene expression of a group of cytokines important for the control of infections in Atlantic salmon (Salmo salar). Particularly, we studied the potential immunomodulatory effects of two flavonoids, Alpinone and Pinocembrine, which were isolated and purified from resinous exudates of Heliotropium huascoense and Heliotropium sinuatum, respectively. The transcript levels of TNF-α and IL-1 (inflammatory cytokines), IFN-γ and IL-12 (T helper 1 type cytokines), IL4/13A (Th2-type cytokine), IL-17 (Th17 type cytokine) TGF-β1 (regulatory cytokine) and IFN-α (antiviral cytokine) were quantified by qRT-PCR in kidneys of flavonoid-treated and control fish. We demonstrated that the administration of a single intramuscular dose of purified Alpinone increased the transcriptional expression of five cytokines, named TNF-α, IL-1, IFN-α, IFN-γ and TGF-β1 in treated fish compared to untreated fish. Conversely, administration of purified Pinocembrine reduced the transcriptional expression of TNF-α, IL-1 and IL-12 in the kidney of treated fish. No other changes were observed. Interestingly, Alpinone also induced in vitro antiviral effects against Infectious Salmon Anaemia virus. Results showed that Alpinone but not Pinocembrine induces the expression of cytokines, which in vertebrates are essential to control viral infections while Pinocembrine reduces pro-inflammatory cytokines. Altogether results suggest that Alpinone is a good candidate to be further tested as immunostimulant and antiviral drug. © 2017 Elsevier Ltd

KW - Alpinone

KW - Anti-inflammatory

KW - Antiviral activity

KW - Atlantic salmon

KW - Cytokines

KW - Flavonoids

KW - IFN alpha

KW - Immunostimulant

KW - ISAV

KW - Pinocembrine

KW - Teleost fish

KW - Th1-type response

KW - alpinone

KW - antivirus agent

KW - flavonoid

KW - gamma interferon

KW - immunomodulating agent

KW - interleukin 1

KW - interleukin 12

KW - interleukin 13

KW - interleukin 13a

KW - interleukin 17

KW - interleukin 4

KW - pinocembrine

KW - transforming growth factor beta1

KW - tumor necrosis factor

KW - unclassified drug

KW - antiviral activity

KW - Article

KW - controlled study

KW - gene expression

KW - Heliotropium

KW - Heliotropium huascoense

KW - Heliotropium sinuatum

KW - infectious salmon anemia

KW - infectious salmon anemia virus

KW - nonhuman

KW - priority journal

KW - reverse transcription polymerase chain reaction

KW - Salmo salar

KW - SHK-1 cell line

U2 - 10.1016/j.fsi.2017.12.043

DO - 10.1016/j.fsi.2017.12.043

M3 - Article

VL - 74

SP - 76

EP - 83

JO - Fish and Shellfish Immunology

T2 - Fish and Shellfish Immunology

JF - Fish and Shellfish Immunology

SN - 1050-4648

ER -