The Combination of Dimorphandra gardneriana Galactomannan and Mangiferin Inhibits Herpes Simplex and Poliovirus

Author(s): Daniele Z. Rechenchoski, Nayara L. Samensari, Ligia C. Faccin-Galhardi, Raimundo R. de Almeida, Arcelina P. Cunha, Nágila M.P.S. Ricardo, Carlos Nozawa, Rosa E.C. Linhares*.

Journal Name: Current Pharmaceutical Biotechnology

Volume 20 , Issue 3 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Background: Herpes simplex virus (HSV) and poliovirus (PV) are both agents of major concern in the public health system. It has been shown that Dimorphandra gardneriana galactomannans can be used as solubilizer vehicles in the manufacturing of medicine. Mangiferin is the major constituent of Mangifera indica and presents multiple medicinal and biological activities.

Objective: This study assayed the effect of D. gardneriana galactomannan combined with mangiferin (DgGmM) against HSV-1 and PV-1.

Methods: The DgGmM cytotoxicity was evaluated by the colorimetric MTT method and the antiviral activity by plaque reduction assay, immunofluorescence and polymerase chain reaction (PCR), in HEp-2 cells.

Results: The DgGmM showed a 50% cytotoxic concentration (CC50) > 2000 µg/mL. The 50% inhibitory concentrations (IC50) for HSV-1 and PV-1 were, respectively, 287.5 µg/mL and 206.2 µg/mL, with selectivity indexes (SI) > 6.95 for the former and > 9.69 for the latter. The DgGmM time-ofaddition protocol for HSV-1 showed a maximum inhibition at 500 µg/mL, when added concomitantly to infection and at the time 1 h post-infection (pi). While for PV-1, for the same protocol, the greatest inhibition, was also observed concomitantly to infection at 500 μg/mL and at the times 4 h and 8 h pi. The inhibition was also demonstrated by the decrease of fluorescent cells and/or the inhibition of specific viral genome.

Conclusion: These results suggested that the DgGmM inhibited HSV-1 and PV-1 replication, with low cytotoxicity and high selectivity and, therefore, represents a potential candidate for further studies on the control of herpes and polio infections.

Keywords: Dimorphandra gardneriana, antiviral, galactomannan, mangiferin, herpesvirus, poliovirus.

Roizman, B.; Knipe, D.M.; Whitley, R.J. Herpes simplex virus.In Fields Virology; Knipe, D.M.; Howley, P.M., Eds.; Lippincott Willians & Wilkins: Philadelphia, 2007, pp. 2502-2601.
WHO: World Health Organization. Globally, an estimated twothirds of the population under 50 are infected with herpes simplex virus type 1. 2015/herpes/en/ (Accessed Feb 22, 2018).
Frobert, E.; Burrel, S.; Ducastelle-Lepretere, S.; Billaud, G.; Ader, F.; Casalegno, J.S.; Nave, V.; Boutolleau, D.; Michallet, M.; Lina, B.; Morfin, F. Resistance of herpes simplex viruses to acyclovir: An update from a tem-year survey in France. Antiviral Res., 2014, 111(1), 36-41.
Racaniello, V.R. Picornaviridae: the viruses and their replication.In Fields Virology; Knipe, D.M.; Howley, P.M., Eds.; Lippincott Williams & Wilkins: Philadelphia, 2007, pp. 796-838.
GPEI: Global Polio Eradication Iniciative. Endemic countries. (Accessed Feb 22, 2018).
Agra, M.D.F.; Freitas, P.F.D.; Barbosa-Filho, J.M. Synopsis of the plants known as medicinal and poisonous in Northeast of Brazil. Rev. Bras. Farmacogn., 2007, 17(1), 114-140.
Ribeiro, D.A.; Oliveira, L.G.S.; Macêdo, D.G.; Menezes, I.R.A.; Costa, J.G.M.; Silva, M.A.P.; Lacerda, S.R.; Souza, M.M.A. Promising medicinal plants for bioprospection in a Cerrado area of Chapada do Araripe, Northeastern Brazil. J. Ethnopharmacol., 2014, 155(3), 1522-1533.
Cunha, P.L.R.; Vieira, Í.G.P.; Arriaga, Â.M.C.; Paula, R.C.M.; Feitosa, J.P.A. Isolation and characterization of galactomannan from Dimorphandra gardneriana Tul. seeds as a potential guar gum substitute. Food Hydrocoll., 2009, 23(3), 880-885.
Schiermeier, S.; Schmidt, P.C. Fast dispersible ibuprofen tablets. Eur. J. Pharm. Sci., 2002, 15(3), 295-305.
Pires, N.R.; Cunha, P.L.R.; Paula, R.C.M.; Feitosa, J.P.A.; Jamacaru, F.V.F.; Filho, M.O.M. Ophthalmic viscosurgical devices: comparison between commercial and formulations based on Dimorphandra gardneriana galactomannan. Quim. Nova, 2010, 33(8), 1709-1713.
Stoilova, I.; Gargova, S.; Stoyanova, A.; Ho, L. Antimicrobial and antioxidant activity of the polyphenol mangiferin. Herba Pol., 2005, 51(1), 37-44.
Garrido, G.; González, D.; Lemus, Y.; García, D.; Lodeiro, L.; Quintero, G.; Delporte, C.; Núnez-Sellés, A.J.; Delgado, R. In vivo and in vitro anti-inflammatory activity of Mangifera indica L. extract (Vimang®). Pharmacol. Res., 2004, 50(2), 143-149.
Garcia, D.; Escalante, M.; Delgado, R.; Ubeira, F.M.; Leiro, J. Anthelminthic and antiallergic activities of Mangifera indica L. stem bark components Vimang and mangiferin. Phytother. Res., 2003, 17(10), 1203-1208.
Perrucci, S.; Fichi, G.; Buggiani, C.; Rossi, G.; Flamini, G. Efficacy of mangiferin against Cryptosporidium parvum in a neonatal mouse model. Parasitol. Res., 2006, 99(2), 184.
Wang, R.R.; Gao, Y.D.; Ma, C.H.; Zhang, X.J.; Huang, C.G.; Huang, J.F.; Zheng, Y.T. Mangiferin, an anti-HIV-1 agent targeting protease and effective against resistant strains. Molecules, 2011, 16(5), 4264-4277.
Yoosook, C.; Bunyapraphatsara, N.; Boonyakiat, Y.; Kantasuk, C. Antiherpes simplex virus activities of crude water extracts of Thai medicinal plants. Phytomedicine, 2000, 6(6), 411-419.
Schmeda-Hirschmann, G.; Arias, A.R. A screening method for natural products on triatomine bugs. Phytother. Res., 1992, 6(2), 68-73.
Ross, I.A. Medicinal plants of the world, chemical constituents, traditional and modern medicinal uses; Humana Press: Totowa, 1999.
Núñez-Sellés, A.J. Antioxidant therapy: Myth or reality? J. Braz. Chem. Soc., 2005, 16(4), 699-710.
Wang, Z.; Deng, J.; Li, X.; Wang, Q. Dissoluble mangiferin inclusion compound and its preparation method. China. Patent CN 101019877-A, Mar 22 2007.
Magbool, F.A.; Elnima, E.I.; Shayoub, M.E.; Hussein, S.O. (2017) Formulation approaches to enhance drug solubility_brief overview. Eur. J. Pharm. Med. Res., 2017, 5(2), 94-100.
O’Brien, M.S.; Markovich, K.C.; Selleseth, D.; DeVita, A.V.; Sethna, P.; Gentry, B.G. In vitro evaluation of current and novel antivirals in combination against human cytomegalovirus. Antiviral Res., 2018, 158, 255-263.
Vieira, I.G.P.; Mendes, F.N.P.; Gallão, M.I.; Brito, E.S. NMR study of galactomannans from the seeds of mesquite tree (Prosopis juliflora (Sw) DC). Food Chem., 2007, 101(1), 70-73.
Barreto, J.C.; Trevisan, M.T.S.; Hull, W.E.; Erben, G.; Brito, E.S.; Pfundstein, B.; Würtele, G.; Spiegelhalder, B.; Owen, R.W. Characterization and quantitation of polyphenolic compounds in bark, kernel, leaves and peel of mango (Mangifera indica L.). J. Agric. Food Chem., 2008, 56(14), 5599-5610.
Almeida, R.R.; Magalhães, H.S.; Souza, J.R.R.; Trevisan, M.T.S.; Vieira, I.G.P.; Feitosa, J.P.A.; Araújo, T.G.; Ricardo, N.M.P.S. Exploring the potential of Dimorphandra gardneriana galactomannans as drug delivery systems. Ind. Crops Prod., 2015, 69(1), 284-289.
Godoi, A.M.; Faccin-Galhardi, L.C.; Lopes, N.; Rechenchoski, D.Z.; Almeida, R.R.; Ricardo, N.M.P.S.; Nozawa, C.; Linhares, R.E.C. Antiviral activity of sulfated polysaccharide of Adenanthera pavonina against poliovirus in HEp-2 cells. Evid. Based Complement. Alternat. Med., 2014, 1-6.
Espada, S.F.; Faccin-Galhardi, L.C.; Rincão, V.P.; Bernardi, A.L.S.; Lopes, N.; Longhini, R.; Mello, J.C.P.; Linhares, R.E.C.; Nozawa, C. Antiviral activity of Trichilia catigua bark extracts for herpesvirus and poliovirus. Curr. Pharm. Biotechnol., 2015, 16(8), 724-732.
Nishimura, T.; Toku, H.; Fukuyasu, H. Antiviral compounds. XII Antiviral activity of amidinohydrazones of alkoxyphenyl-substituted carbonyl compounds against influenza virus in eggs and in mice. Kitasato Arch. Exp. Med., 1977, 50(1-2), 39-46.
Faccin-Galhardi, L.C.; Yamamoto, K.A.; Ray, S.; Ray, B.; Linhares, R.E.C.; Nozawa, C. The in vitro antiviral property of Azadirachta indica polysaccharides for poliovirus. J. Ethnopharmacol., 2012, 142(1), 86-90.
Minari, M.C.; Rincão, V.P.; Soares, S.A.; Ricardo, N.M.P.S.; Nozawa, C.; Linhares, R.E.C. Antiviral properties of polysaccharides from Agaricus brasiliensis in the replication of bovine herpesvirus 1. Acta Virol., 2011, 55(3), 255-259.
Lopes, N.; Faccin-Galhardi, L.C.; Espada, S.F.; Ricardo, N.M.P.S.; Linhares, R.E.C.; Nozawa, C. Sulfated polysaccharide of Caesalpinia ferrea inhibits herpes simplex virus and poliovirus. Int. J. Biol. Macromol., 2013, 60(1), 93-99.
Faccin, L.C.; Benati, F.; Rincão, V.P.; Mantovani, M.S.; Soares, S.A.; Gonzaga, M.L.; Nozawa, C.; Linhares, R.E.C. Antiviral activity of aqueous and ethanol extracts and of an isolated polysaccharide from Agaricus brasiliensis against poliovirus type 1. Lett. Appl. Microbiol., 2007, 45(1), 24-28.
Sauerbrei, A.; Deinhardt, S.; Zell, R.; Wutzler, P. Phenotypic and genotypic characterization of acyclovir-resistant clinical isolates of herpes simplex virus. Antiviral Res., 2010, 86(3), 246-252.
Amani, H.; Habibey, R.; Hajmiresmail, S.J.; Latifi, S.; Pazoki-Toroudi, H.; Akhavan, O. (2017) Antioxidant nanomaterials in advanced diagnoses and treatments of ischemia reperfusion injuries. J. Mater. Chem. B., 2017, 5(48), 9452-9476.
Wigg, M.D.; Miranda, M.M.F.S. Viroses dermotrópicas. In: Introdução à Virologia Humana;, Santos, N.O.S.; Romanos, M.T.V.; Wigg, M.D., Ed.; Guanabara Koogan: Rio de Janeiro, 2008; pp. 177-211.
Marques, M.M.M.; Morais, S.M.; Silva, A.R.A.; Barroso, N.D.; Filho, T.R.P.; Araújo, F.M.C.; Vieira, I.G.P.; Lima, D.M.; Guedes, M.I.F. Antiviral and antioxidant activities of sulfated galactomannans from plants of Caatinga biome. Evid. Based Complement. Alternat. Med., 2015, •••, 1-8.
Zhu, X.M.; Song, J.X.; Huang, Z.Z.; Wu, Y.M.; Yu, M.J. Antiviral activity of mangiferin against herpes simplex virus type 2 in vitro. Acta Pharmacol. Sin., 1993, 14(5), 452-454.
Ryu, Y.B.; Curtis-Long, M.J.; Lee, J.W.; Kim, J.Y.; Kang, K.Y.; Lee, W.S.; Park, K.H. Characteristic of neuraminidase inhibitory xanthones from Cudrania tricuspidata. Bioorg. Med. Chem., 2009, 17(7), 2744-2750.
Sitohy, M.; Dalgalarrondo, M.; Nowoczin, M.; Besse, B.; Billaudel, S.; Haertlé, T.; Chobert, J.M. The effect of bovine whey proteins on the ability of poliovirus and Coxsackie virus to infect Vero cells cultures. Int. Dairy J., 2008, 18(6), 658-668.
Witvrouw, M.; Este, J.A.; Mateu, M.Q.; Reymen, D.; Andrei, G.; Snoeck, R.; Ikeda, S.; Pauwells, R.; Bianchini, N.V.; Desmyter, J.; De Clercq, E. Activity of a sulfated polysaccharide extracted from the red seaweed Aghardhiella tenera against human immunodeficiency virus and other enveloped viruses. Antivir. Chem. Chemother., 1994, 5(5), 297-303.
Hidari, K.I.P.J.; Takahashi, N.; Arihara, M.; Nagaoka, M.; Morita, K.; Suzuki, T. Structure and anti-dengue virus activity of sulfated polysaccharide from a marine alga. Biochem. Biophys. Res. Commun., 2008, 376(1), 91-95.
Chrestani, F.; Sierakowski, M.R.; Uchoa, D.E.A.; Nozawa, C.; Sassaki, G.L.; Gorin, P.A.J.; Ono, L. In vitro antiherpetic and antirotaviral activities of a sulfate prepared from Mimosa scabrella galactomannan. Int. J. Biol. Macromol., 2009, 45(5), 453-457.
Tong, X.K.; Qiu, H.; Zhang, X.; Shi, L.P.; Wang, G.F.; Ji, F.H.; Ding, H.Y.; Tang, W.; Ding, K.; Zuo, J.P. WSS45, a sulfated α-D-glucan, strongly interferes with dengue 2 virus infection in vitro. Acta Pharmacol. Sin., 2010, 31(5), 585-592.
Ichiyama, K.; Reddy, S.B.G.; Zhang, L.F.; Chin, W.X.; Muschin, T.; Heinig, L.; Suzuki, Y.; Nanjundappa, H.; Yoshinaka, Y.; Ryo, A.; Nomura, N.; Ooi, E.E.; Vasudevan, S.G.; Yoshida, T.; Yamamoto, N. Sulfated polysaccharide, curdlan sulfate, efficiently prevents entry/fusion and restricts antibody-dependent enhancement of dengue virus infection in vitro: A possible candidate for clinical application. PLoS Negl. Trop. Dis., 2013, 7(4), e2188.
Amani, H.; Ajami, M.; Maleki, S.N.; Pazoki-Toroudi, H.; Daglia, M.; Sokeng, A.J.T.; Lorenzo, A.D.; Nabavi, S.F.; Devi, K.P.; Nabavi, S.M. Targeting signal transducers and activators of transcription (STAT) in human cancer by dietary polyphenolic antioxidants. Biochimie, 2017, 142, 63-79.
Medina-Gali, R.M.; Ortega-Villazain, M.D.M.; Mercado, L.; Novoa, B.; Coll, J.; Perez, L. Beta-glucan enhances the response to SVCV infection in zebrafish. Dev. Comp. Immunol., 2018, 7(84), 307-314.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [215 - 221]
Pages: 7
DOI: 10.2174/1389201020666190307130431
Price: $65

Article Metrics

PDF: 26
HTML: 14
PRC: 1