Abstract
Dengue is the most important viral infection transmitted among humans by arthropod-borne. There are currently no vaccines or specific therapeutical treatment. Therefore, immunomodulatory compounds from plants have been widely examined for their antiviral effects. Cissampelos sympodialis Eichler. Menis-permaceae. has scientifically proven to present immunomodulatory activities. Here we assessed the antiviral activity of leaf hydroalcoholic extract, warifteine or methylwarifteine from C sympodialis in an in vitro dengue virus infection model. The results demonstrated that leaf hydroalcoholic extract or warifteine/methyI warifteine treatment did not reduce dengue virus-Ag+ hepatocyte (Huh-7 cell) rates in present experimental conditions. However, we assessed the potential antiviral effect of leaf hydroalcoholic extract or warifteine/methylwarifteine on dengue virus-infection by the production of inflammatory molecules. TNF-α. MIF. IL-8 and PGE2. Dengue virus infection enhanced TNF-α. MIF. IL-8 and PGE2 production in infected Huh-7 cells and leaf hydroalcoholic extract but not warifteine/methylwarifteine treatments, significantly reduced these molecules in infected cells. In dengue virus-infected Huh-7 cells. non-structural protein-1 is produced and leaf hydroalcoholic extract significantly inhibited it independently of alkaloids. Our findings imply that leaf hydroalcoholic extract may attenuate dengue virus infection in Huh-7 cells by inhibiting the enhanced of pro-inflammatory mediators and non-structural protein-1 production induce by dengue virus independently of warifteine/methywarifteine its major compound.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Abd Kadir, S.L., Yaakob, H., Mohamed Zulkifli, R., 2013. Potential anti-dengue medicinal plants: a review. J. Nat. Med. 67, 677–689.
Amorim, J.H., Alves, R.P., Boscardin, S.B., Ferreira, LC., 2014. The dengue virus nonstructural 1 protein: risks and benefits. Virus Res. 181, 53–60.
Assuncao-Miranda, I., Amaral, F.A., Bozza, F.A., Fagundes, CT., Sousa, LP., Souza, D.G., Pacheco, P., Barbosa-Lima, G., Gomes, R.N., Bozza, P.T., Da Poian, A.T., Teixeira, M.M., Bozza, M.T., 2010. Contribution of macrophage migration inhibitory factor to the pathogenesis of dengue virus infection. FASEBJ. 24, 218–228.
Braga, E.L., Moura, P., Pinto, L.M., Ignacio, S.R., Oliveira, M.J., Cordeiro, M.T., Kubelka, CF., 2001. Detection of circulant tumor necrosis factor-alpha, soluble tumor necrosis factor p75 and interferon-gamma in Brazilian patients with dengue fever and dengue hemorrhagic fever. Mem. Inst. Oswaldo Cruz 96, 229–232.
Cerqueira-Lima, A.T., Alcantara-Neves, N.M., de Carvalho, L.C., Costa, R.S., Barbosa-Filho, J.M., Piuvezam, M., Momtchilo, R., Barboza, R., de Jesus Oliveira, E., Marinho, A., Figueiredo, CA., 2010. Effects of Cissampelos sympodialis Eichl. and its alkaloid warifteine, in an experimental model of respiratory allergy to Blomia tropicalis. Curr. Drug Targets 11, 1458–1467.
Chen, H.-C., Hofman, F.M., Kung, J.T., Lin, Y.D., Wu-Hsieh, B.A., 2007. Both virus and tumor necrosis factor alpha are critical for endothelium damage in a mouse model of dengue virus-induced hemorrhage. J. Virol. 81, 5518–5526.
De Freitas, M.R., Cortes, S.F., Thomas, G., Barbosa Filho, J.M., 1996. Modification of Ca2+ metabolism in the rabbit aorta as a mechanism of spasmolytic action of warifteine a bisbenzylisoquinoline alkaloid isolated from the leaves of Cissampelos sympodialis Eichl. (Menispermaceae). J. Pharm. Pharmacol. 48, 332–336.
Lima-Junior, R.S., Mello Cda, S., Siani, A.C., Valente, L.M., Kubelka, CF., 2013. Uncaria tomentosa alkaloidal fraction reduces paracellular permeability. IL-8 and NS1 production on human microvascular endothelial cells infected with dengue virus. Nat. Prod. Commun. 8, 1547–1550.
Liou, J.T., Chen, Z.Y., Ho, L.J., Yang, S.P., Chang, D.M., Liang, CC., Lai, J.H., 2008. Differential effects of triptolide and tetrandrine on activation of COX-2. NF-kappaB, and AP1 and virus production in dengue virus-infected human lung cells. Eur. J. Pharmacol. 589, 288–298.
Melo, P.S., de Medeiros Cavalcante, H.M., Barbosa-Filho, J.M., de Fatima Formiga Melo Diniz, M., de Medeiros, I.A., Haun, M., 2003. Warifteine and milonine, alkaloids isolated from Cissampelos sympodialis Eichl: cytotoxicity on rat hepatocyte culture and in V79 cells. Toxicol. Lett. 142, 143–151.
Mosmann, T., 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods 65, 55–63.
Perez, A.B., Sierra, B., Garcia, G., Aguirre, E., Babel, N., Alvarez, M., Sanchez, L., Valdes, L., Volk, H.D., Guzman, M.G., 2010. Tumor necrosis factor-alpha transforming growth factor-beta1, and interleukin-10 gene polymorphisms: implication in protection or susceptibility to dengue hemorrhagic fever. Hum. Immunol. 71, 1135–1140.
Piuvezam, M.R., Bezerra-Santos, CR., Bozza, P.T., Bandeira-Melo, C., Vieira, G.C., Costa, H.F., 2012. Cissampelos sympodialis (Menispermaceae): a novel phytotherapic weapon against allergic diseases? In: Pereira, C. (Ed.), Allergic Diseases -Highlights in the Clinic, Mechanisms and Treatment. InTech, Croatia, p. 554.
Piuvezam, M.R., Peçanha, L.M.T., Alexander, J., Thomas, G., 1999. Cissampelos sympodialis Eichl leaf extract increases the production of IL10 by concanavalin-A-treated BALB/c spleen cells. J. Ethnopharmacol. 67, 93–101.
Purwati, Nasronudin, Kusumowidagdo, E.R., Rantam, F.A., 2011. The relation between levels of TNF-alpha, IL-1beta PGE2 and PLA2 with the severity degree of dengue hemorrhagic. Microbiol. Indones. 5, 5.
Raghupathy, R., Chaturvedi, U.C., Al-Sayer, H., Elbishbishi, E.A., Agarwal, R., Nagar, R., Kapoor, S., Misra, A., Mathur, A., Nusrat, H., Azizieh, F., Khan, M.A., Mustafa, A.S., 1998. Elevated levels of IL-8 in dengue hemorrhagic fever. J. Med. Virol. 56, 280–285.
Reis, S.R., Valente, L.M., Sampaio, A.L., Siani, A.C., Gandini, M., Azeredo, E.L., D’Avila, LA., Mazzei, J.L., Henriques, M., Kubelka, CF., 2008. Immunomodulating and antiviral activities of Uncaria tomentosa on human monocytes infected with Dengue Virus-2. Int. Immunopharmacol. 8, 468–476.
Rocca, B., FitzGerald, G.A., 2002. Cyclooxygenases and prostaglandins: shaping up the immune response. Int. Immunopharmacol. 2, 603–630.
Sellahewa, K.H., 2013. Pathogenesis of dengue haemorrhagic fever and its impact on case management. ISRN Infect. Dis. 2013, 6.
Shresta, S., Sharar, K.L., Prigozhin, D.M., Beatty, P.R., Harris, E., 2006. Murine model for dengue virus-induced lethal disease with increased vascular permeability. J. Virol. 80, 10208–10217.
Steer, S.A., Corbett, J.A., 2003. The role and regulation of COX-2 during viral infection. Viral Immunol. 16, 447–460.
Tsatsanis, C., Androulidaki, A., Venihaki, M., Margioris, A.N., 2006. Signalling networks regulating cyclooxygenase-2. Int. J. Biochem. Cell Biol. 38, 1654–1661.
Vieira, G.C, De Lima, J.F., De Figueiredo, R.C.B.Q., Mascarenhas, S.R., Bezerra-Santos, CR., Piuvezam, M.R., 2013. Inhaled Cissampelos sympodialis down-regulates airway allergic reaction by reducing lung CD3+T cells. Phytother. Res. 27, 916–925.
Acknowledgments
This study was financially supported by CNPq-Universal14/2012-472853/2012-0; CAPES/Brazil; PROEP, IOC and Plataforma Tecnológica (RPT11D)/FIOCRUZCSM, LGF and CM are graduated students at Posgbp IOC, Fiocruz.
Author information
Authors and Affiliations
Contributions
FCL, CFM and LGF (PhD students) contributed to the development of the biological protocols. CSM and ALAL (MS students) contributed to the ELISA assay. JMBF contributed in plant identification and alkaloid isolation. CFK and MRP designed the study, supervised the laboratory work and contributed to critical reading of the manuscript.
Corresponding author
Ethics declarations
The authors declare no conflicts of interest.
Rights and permissions
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Leite, F.C., Mello, C.d.S., Fialho, L.G. et al. Cissampelos sympodialis has anti-viral effect inhibiting dengue non-structural viral protein-1 and pro-inflammatory mediators. Rev. Bras. Farmacogn. 26, 502–506 (2016). https://doi.org/10.1016/j.bjp.2016.03.013
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1016/j.bjp.2016.03.013