Therapeutic efficacy in BALB/C mice of extract from marine alga Canistrocarpus cervicornis (Phaeophyceae) against herpes simplex virus type 1
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Abstract
Studies with diterpenes from marine brown alga Canistrocarpus cervicornis showed the antiviral potential of the products from this alga in controlling the replication of HSV-1 and maintaining low cytotoxicity. Hence, the aim of this work was to evaluate the anti-herpetic efficacy of C. cervicornis extract ointment in BALB/c mice. To test the anti-herpetic efficacy in vivo, four groups of BALB/c mice (n = 5) were used: 1—untreated, 2—extract ointment (2 % or 0.4 mg cm−2 dose−1), 3—Acyclovir cream (5 % or 1.0 mg cm−2 dose−1), and 4—ointment base. The right midflank of each mouse was clipped and depilated with a chemical depilatory. After 2 days, the skin area was scratched and inoculated with HSV-1. The ointments and cream were applied three times a day over a 16-day period, beginning 1 h after virus inoculation. The development of skin lesions was continuously monitored and scored. To evaluate the effect of C. cervicornis topical treatment on biochemical parameters and on body weight, two uninfected groups were formed: an untreated group and a group treated with ointment C. cervicornis extract (2 %). The signs of infection appeared from the second day after infection, while on the 10th day of the experiment, the ointment base and untreated groups had significantly more severe lesions than did the groups that were treated with extract (p < 0.05) or acyclovir (p < 0,01). The topical application of extract ointment did not change body weight, hepatic, or renal function suggesting that the extract has a low toxicity in this route of administration. These results suggest that the extract may be useful in reducing the severity of HSV-1 cutaneous lesions.
Keywords
Canistrocarpus cervicornis Phaeophyceae HSV-1 Marine natural product AntiviralNotes
Acknowledgments
The authors are grateful to CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) for the financial support and for Productivity Fellowships to ICNPP (303368/2013-6) and VLT (301420/2010-6). ICNPP (E-26/103.024/2011) and VLT (E-26/103.176/2011) also thank the FAPERJ (Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro) for the Cientista do Nosso Estado Fellowship. CSB thanks FAPERJ for the DSc fellowship (E-26/100.770/2012). MWLG thanks FAPERJ for the fellowship (E-26/200.712/2015).
References
- Barros CdS, Teixeira VL, Paixão ICN (2015a) Seaweeds with anti-herpes simplex virus type 1 activity. J Appl Phycol 27:1623–1637Google Scholar
- Barros CdS, Cirne-Santos CC, Garrido V, Barcelos I, Stephens PRS, Giongo V, Teixeira VL, de Palmer Paixão ICN (2015b) Anti-HIV-1 activity of compounds derived from marine alga Canistrocarpus cervicornis. J Appl Phycol doi: 10.1007/s10811-015-0776-1
- Cardozo F, Larsen I, Carballo E, Jose G, Stern R, Brummel R, Camelini C, Rossi M, Simões C, Brandt C (2013) In vivo anti-herpes simplex virus activity of a sulfated derivative of Agaricus brasiliensis mycelial polysaccharide. Antimicrob Agents Chhemother 57:2541–2549Google Scholar
- de Oliveira AS, Cavalcanti DN, Bianco EM, de Paula JC, Pereira RC, Yoneshigue-Valentin Y, Teixeira VL (2008) Chemical composition of diterpenes from the brown alga Canistrocarpus cervicornis (Dictyotaceae, Phaeophyceae). Nat Prod Commun 3:1469–1472Google Scholar
- De-Paula JC, de Gusmão Pedrini A, Pinheiro MD, Pereira RC, Teixeira VL (2001) Chemical similarity between the brown algae Dictyota cervicornis and D. pardalis (Dictyotales, Phaeophyta). Biochem Syst Ecol 29:425–427CrossRefPubMedGoogle Scholar
- Fernandes DRP, de Oliveira VP, Valentin YY (2014) Seaweeds biotechnology in Brazil: six decades of studies on natural products and their antibiotic and other biological activities. J Appl Phycol 26:1923–1937CrossRefGoogle Scholar
- Hussin A, Md Nor NS, Ibrahim N (2013) Phenotypic and genotypic characterization of induced acyclovir-resistant clinical isolates of herpes simplex virus type 1. Antivir Res 100:306–313CrossRefPubMedGoogle Scholar
- Karampuri S, Bag P, Yasmin S, Chouhan DK, Bal C, Mitra D, Chattopadhyay D, Sharon A (2012) Structure based molecular design, synthesis and biological evaluation of alpha-pyrone analogs as anti-HSV agent. Bioorg Med Chem Lett 22:6261–6266CrossRefPubMedGoogle Scholar
- Kelecom A, Teixeira VL (1988) Dolastane diterpenes from the marine brown alga Dictyota cervicornis. Phytochemistry 27:2907–2909CrossRefGoogle Scholar
- Lipipun V, Sasivimolphan P, Yoshida Y, Daikoku T, Sritularak B, Ritthidej G, Likhitwitayawuid K, Pramyothin P, Hattori M, Shiraki K (2011) Topical cream-based oxyresveratrol in the treatment of cutaneous HSV-1 infection in mice. Antivir Res 91:154–160CrossRefPubMedGoogle Scholar
- Looker KJ, Magaret AS, May MT, Turner KM, Vickerman P, Gottlieb SL, Newman LM (2015) Global and regional estimates of prevalent and incident Herpes Simplex Virus Type 1 infections in 2012. PLoS one 10(10), e0140765Google Scholar
- Nakama S, Tamaki K, Ishikawa C, Tadano M, Mori N (2012) Efficacy of Bidens pilosa extract against Herpes Simplex Virus infection in vitro and in vivo. Evid Based Complement Alternat Med 2012:413453CrossRefPubMedPubMedCentralGoogle Scholar
- Park H-J, Kurokawa M, Shiraki K, Nakamura N, Choi J-S, Hattori M (2005) Antiviral activity of the marine alga Symphyocladia latiuscula against herpes simplex virus (HSV-1) in vitro and its therapeutic efficacy against HSV-1 infection in mice. Biol Pharm Bull 28:2258–2262CrossRefPubMedGoogle Scholar
- Piret J, Boivin G (2011) Resistance of herpes simplex viruses to nucleoside analogues: mechanisms, prevalence, and management. Antimicrob Agents Chemother 55:459–472CrossRefPubMedGoogle Scholar
- Roy S, Majumdar S, Singh AK, Ghosh B, Ghosh N, Manna S, Chakraborty T, Mallick S (2015) Synthesis, characterization, antioxidant status, and toxicity study of vanadium–rutin complex in Balb/c mice. Biol Trace Elem Res 166:183–200CrossRefPubMedGoogle Scholar
- Santos S, Rangel E, Lima J, Silva R, Lopes L, Noldin V, Monache FD, Martins D (2009) Toxicological and phytochemical studies of Aspidosperma subincanum Mart. stem bark (Guatambu). Pharmazie 64:836–839PubMedGoogle Scholar
- Sasivimolphan P, Lipipun V, Ritthidej G, Chitphet K, Yoshida Y, Daikoku T, Sritularak B, Likhitwitayawuid K, Pramyothin P, Hattori M, Shiraki K (2012) Microemulsion-based oxyresveratrol for topical treatment of herpes simplex virus (HSV) infection: physicochemical properties and efficacy in cutaneous HSV-1 infection in mice. AAPS PharmSciTech 13:1266–1275CrossRefPubMedPubMedCentralGoogle Scholar
- Teixeira V, Tomassini T, Kelecom A (1986a) Cervicol, a further secodolastane diterpene from the marine brown alga Dictyota cervicornis Kützing (Phaeophyceae, Dictyotaceae). Bull Soc Chim Belg 95:263–268CrossRefGoogle Scholar
- Teixeira VL, Tomassini T, Fleury BG, Kelecom A (1986b) Dolastane and secodolastane diterpenes from the marine brown alga, Dictyota cervicornis. J Nat Prod 49:570–575CrossRefGoogle Scholar
- Vallim MA, Barbosa JE, Cavalcanti DN, De-Paula JC, Silva V, Teixeira VL, Paixão I (2010) In vitro antiviral activity of diterpenes isolated from the Brazilian brown alga Canistrocarpus cervicornis. J Med Plant Res 4:2379–2382Google Scholar
- WHO (2016) Globally, an estimated two-thirds of the population under 50 are infected with herpes simplex virus type 1. World Health Organization. http://www.who.int/mediacentre/news/releases/2015/herpes/en/. Accessed 4th, January 2016