In vitro anti-Herpes simplex virus activity of crude extract of the roots of Nauclea latifolia Smith (Rubiaceae)

BMC Complementary and Alternative Medicine

David Lembo³  Carlo Bicchi¹  Patrizia Rubiolo¹  Fabrice Fekam Boyom⁷  Cecilia Cagliero¹  Valeria Cagno⁶  Roberta Rovito⁶  Alembert Tiabou Tchinda⁵  Donatien Gatsing²  Rosalie Annie Ngono Ngane⁴  Huguette Magnifouet Nana²  Manuela Donalisio⁶ 

[1] Laboratory of Phytoanalysis, Department of Drug Science and Technology, University of Turin, PO Box 10125, Torino, Italy;Laboratory of Microbiology and Antimicrobial Substances, University of Dschang, PO Box 67, Dschang, Cameroon;Department of Clinical and Biological Sciences, University of Turin, S. Luigi Gonzaga Hospital, Regione Gonzole, 10, 10043 Orbassano, Turin, Italy;Laboratory of Biochemistry, University of Douala, PO Box 24157, Douala, Cameroon;Laboratory of Phytochemistry, Institute of Medical Research and Medicinal Plants Studies, PO Box 6163, Yaoundé, Cameroon;Laboratory of Molecular Virology, Department of Clinical and Biological Sciences, University of Turin, PO Box 10043, Torino, Italy;Laboratory of Phytobiochemistry and medicinal plants study, Department of Biochemistry, University of Yaoundé, PO Box 812, Yaoundé, Cameroon

关键词: HSV-2;    Antiviral activity;    Phytochemistry;    CH₂Cl₂/MeOH extract;    N. latifolia roots;   

Others  :  1220894
DOI  :  10.1186/1472-6882-13-266

 received in 2013-05-02, accepted in 2013-09-24,  发布年份 2013

【 摘 要 】

Background

Nauclea latifolia Smith, a shrub belonging to the family Rubiaceae is a very popular medicinal plant in Cameroon and neighboring countries where it is used to treat jaundice, yellow fever, rheumatism, abdominal pains, hepatitis, diarrhea, dysentery, hypertension, as well as diabetes. The ethno-medicinal use against yellow fever, jaundice and diarrhea prompted us to investigate on the antiviral activity of the root bark of N. latifolia. In this study, HSV-2 was chosen as a viral model because of its strong impact on HIV transmission and acquisition.

Methods

The crude extract under study was prepared by maceration of air-dried and powdered roots barks of N. latifolia in CH₂Cl₂/MeOH (50:50) mixture for 48 hours, then it was subjected to filtration and evaporation under vacuum. A phytochemical analysis of the crude extract was performed by High Performance Liquid Chromatography coupled with a photodiode array and mass spectrometry (HPLC-PDA-ESI-qMS). The anti-HSV-2 activity was assayed in vitro by plaque reduction and virus yield assays and the major mechanism of action was investigated by virucidal and time of addition assays. Data values were compared using the Extra sum of squares F test of program GraphPad PRISM 4.

Results

The main components detected in the extract belong to the class of indole alkaloids characteristic of Nauclea genus. Strictosamide, vincosamide and pumiloside were tentatively identified together with quinovic acid glycoside. N. latifolia crude extract inhibited both acyclovir sensitive and acyclovir resistant HSV-2 strains, with IC₅₀ values of 5.38 μg/ml for the former and 7.17 μg/ml for the latter. The extract was found to be most active when added post-infection, with IC₅₀ of 3.63 μg/ml.

Conclusion

The results of this work partly justify the empirical use of N. latifolia in traditional medicine for the treatment of viral diseases. This extract could be a promising rough material for the development of a new and more effective modern anti-HSV-2 medication also active against acyclovir-resistant HSV-2 strains.

【 授权许可】

   
2013 Donalisio et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Whitley RJ, Roizman B: Herpes simplex virus infections. Lancet 2001, 357:1513-1518.
• [2]Stanberry LR, Cunningham AL, Mindel A, Scott LL, Spruance SL, Aoki FY, Lacey CJ: Prospects for control of herpes simplex virus disease through immunization. Clin Infect Dis 2000, 30:549-566.
• [3]Brown ZA, Selke S, Zeh J, Kopelman J, Maslow A, Ashley RL, Watts DH, Berry S, Herd M, Corey L: The acquisition of herpes simplex virus during pregnancy. N Engl J Med 1997, 337:509-515.
• [4]Looker KJ, Garnett GP, Schmid GP: An estimate of the global prevalence and incidence of herpes simplex virus type 2 infection. Bull World Health Organ 2008, 86:805-812.
• [5]Wald A, Link K: Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: a meta-analysis. J Infect Dis 2002, 185:45-52.
• [6]Greenberg MS, Friedman H, Cohen SG, Oh SH, Laster L, Starr S: A comparative study of herpes simplex infections in renal transplant and leukemic patients. J Infect Dis 1987, 156:280-287.
• [7]Carr DJ, Tomanek L: Herpes simplex virus and the chemokines that mediate the inflammation. Curr Top Microbiol Immunol 2006, 303:47-65.
• [8]Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ: Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. Aids 2006, 20:73-83.
• [9]Corey L, Wald A, Celum CL, Quinn TC: The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: a review of two overlapping epidemics. J Acquir Immune Defic Syndr 2004, 35:435-445.
• [10]Brady RC, Bernstein DI: Treatment of herpes simplex virus infections. Antiviral Res 2004, 61:73-81.
• [11]Gupta R, Warren T, Wald A: Genital Herpes. Lancet. 2007, 370:2127-2137.
• [12]Bacon TH, Boon RJ, Schultz M, Hodges-Savola C: Surveillance for antiviral-agent-resistant herpes simplex virus in the general population with recurrent herpes labialis. Antimicrob Agents Chemother 2002, 46:3042-3044.
• [13]Khan MT, Ather A, Thompson KD, Gambari R: Extracts and molecules from medicinal plants against herpes simplex viruses. Antiviral Res 2005, 67(2):107-19.
• [14]Bringmann G, Pokorny F: The Naphthylisoquinoline alkaloids. In The Alkaloids. Volume 46. Edited by Cordell G. New York: Academic University Press; 1995::127-271.
• [15]Adjanohoun JE, Aboubakar N, Dramane K, Ebot ME, Ekpere JA, Enow-Orock EG, Focho D, Gbilé ZO, Kamanyi A, Kamsu KJ, Keita A, Mbenkum T, Mbi CN, Mbiele AL, Mbome IL, Mubiru NK, Nancy WL, Nkongmeneck B, Satabié B, Sofowora A, Tamze V, Wirmum CW: Contribution to Ethnobotanical and Floristic Studies in Cameroon. Addis Ababa: CSTR/OUA; 1996.
• [16]Okwori AEJ, Okeke CI, Uzoechina A, Etukudoh NS, Amali MN, Adetunji JA, Olabode AO: The antibacterial potentials of Nauclea latifolia. Afr J Biotechnol 2008, 7:1394-1399.
• [17]Gidado A, Ameh DA, Atawodi SE: Effect of Nauclea latifolia leaves aqueous extracts on blood glucose levels of normal and alloxan-induced diabetic rats. Afr J Biotech 2005, 4:91-93.
• [18]Benoit-Vical F, Valentin A, Cournac V, Pélissier Y, Mallié M, Bastide JM: In vitro antiplasmodial activity of stem and root extracts of Nauclea latifolia S.M. (Rubiaceae). J Ethnopharmacol 1998, 61:173-178.
• [19]Ngnokam D, Ayafor JF, Connolly JD, Nuzillard JM: Nauclefolinine: a new alkaloid from the roots of Nauclea latifolia. Bull Chem Soc Ethiop 2003, 17:173-176.
• [20]Shigemori H, Kagata T, Ishiyama H, Morah F, Ohsaki A, Kobayashi J: Naucleamides A-E, new monoterpene indole alkaloids from Nauclea latifolia. Chem Pharm Bull 2003, 51:58-61.
• [21]Abreu P, Pereira A: New indole alkaloids from Sarcocephaleus latifolius. Nat Prod Lett 2001, 15:43-48.
• [22]Field HJ, Darby G, Wildy P: Isolation and characterization of acyclovir-resistant mutants of herpes simplex virus. J Gen Virol 1980, 49(1):115-24.
• [23]Cavalli R, Donalisio M, Bisazza A, Civra A, Ranucci E, Ferruti P, Lembo D: Enhanced antiviral activity of acyclovir loaded into nanoparticles. Methods of Enzymology 2012, 509:1-19.
• [24]Lembo D, Swaminathan S, Donalisio M, Civra A, Pastero L, Aquilano D, Vavia P, Trotta F, Cavalli R: Encapsulation of Acyclovir in new carboxylated cyclodextrin-based nanosponges improves the agent's antiviral efficacy. Int J Pharm 2013, 443:262-272.
• [25]Shogan B, Kruse L, Mulamba GB, Hu A, Coen DM: Virucidal activity of a GT-rich oligonucleotide against herpes simplex virus mediated by glycoprotein B. J Virol 2006, 80:4740-4747.
• [26]Donalisio M, Rusnati M, Cagno V, Civra A, Bugatti A, Giuliani A, Pirri G, Volante M, Papotti M, Landolfo S, Lembo D: Inhibition of human respiratory syncytial virus infectivity by a dendrimeric heparan sulfate-binding peptide. Antimicrob Agents Chemother 2012, 56:5278-5288.
• [27]Erdelmeier CAJ, Wright AD, Orjala J, Baumgartner B, Rali T, Sticher O: New indole alkaloid glycosides from Nauclea latifolia. Planta Med 1991, 57:149-152.
• [28]Zhang Z, ElSohly HN, Jacob MR, Pasco DS, Walker LA, Clark AM: New indole alkaloids from the bark of Nauclea orientalis. J Nat Prod 2001, 64:1001-1005.
• [29]Aquino R, De Tommasi T, De Simone F, Pizza C: Triterpenes and quinovic acid glycosides from Uncaria tomentosa. Phytochemistry 1997, 45:1035-1040.
• [30]Shieh MT, WuDunn D, Montgomery RI, Esko JD, Spear PG: Cell surface receptors for herpes simplex virus are heparan sulfate proteoglycans. J Cell Biol 1992, 116:1273-1281.
• [31]Karou SD, Tchacondo T, Ilboudo DP, Simpore J: Sub-Saharan Rubiaceae: a review of their traditional uses, phytochemistry and biological activities. Pak J Biol Sci 2011, 14:149-169.
• [32]Tekwu EM, Pieme AC, Beng VP: Investigations of antimicrobial activity of some Cameroonian medicinal plant extracts against bacteria and yeast with gastrointestinal relevance. J Ethnopharmacol 2012, 142:265-273.
• [33]Taïwe GS, Bum EN, Talla E, Dimo T, Weiss N, Sidiki N, Dawe A, Moto FC, Dzeufiet PD, De Waard M: Antipyretic and antinociceptive effects of Nauclea latifolia root decoction and possible mechanisms of action. Pharm Biol 2011, 49:15-25.
• [34]Abbah J, Amos S, Chindo B, Ngazal I, Vongtau HO, Adzu B, Farida T, Odutola AA, Wambebe C, Gamaniel KS: Pharmacological evidence favouring the use of Nauclea latifolia in malaria ethnopharmacy: effects against nociception, inflammation, and pyrexia in rats and mice. J Ethnopharmacol 2010, 127:85-90.
• [35]Mbopi-Keou FX, Gresenguet G, Mayaud P, Weiss HA, Gopal R, Matta M, Paul JL, Brown DW, Hayes RJ, Mabey DC, Bélec L: Interactions between herpes simplex virus type 2 and human immunodeficiency virus type 1 infection in African women: opportunities for intervention. J Infect Dis 2000, 182:1090-1096.
• [36]Serwadda DGray RHSewankambo NKWabwire-Mangen F, Chen MZ, Quinn TC, Lutalo T, Kiwanuka N, Kigozi G, Nalugoda F, Meehan MP, Ashley Morrow R, Wawer MJ: Human immunodeficiency virus acquisition associated with genital ulcer disease and herpes simplex virus type 2 infection: a nested case–control study in Rakai, Uganda. J Infect Dis 2003, 188:1492-1497.
• [37]Celum CL, Robinson NJ, Cohen MS: Potential effect of HIV type 1 antiretroviral and herpes simplex virus type 2 antiviral therapy on transmission and acquisition of HIV type 1 infection. J Infect Dis 2005, 191:S107-114.
• [38]White RG, Freeman EE, Orroth KK, Bakker R, Weiss HA, O'Farrell N, Buvé A, Hayes RJ, Glynn JR: Population-level effect of HSV-2 therapy on the incidence of HIV in sub-Saharan Africa. Sex Transm Infect 2008, 84:ii12-8.