Antiviral activity of Eucalyptus camaldulensis leaves ethanolic extract on herpes viruses infection

Main Article Content

Aya Abu-Jafar
Mahmoud Huleihel

Abstract

Eucalyptus camaldulensis (Ec) is considered as a traditional medicinal plant with valuable therapeutic effects. Here we evaluated the antiviral activity of its ethanolic leave extract on different herpes viruses. Vero cells were infected with either of the tested viruses [herpes simplex virus -1 and 2 (HSV-1, HSV-2) and Varicella-Zoster Virus (VZV)] with or without treatment with Ec extract and viral infection development was evaluated by plaque assay. Our results showed significant antiviral activity of the examined extract against all tested viruses. The 80%-MeOH fraction of this extract offered the highest activity against these viruses with 50% inhibitory concentration (IC50) of 0.1±0.08, 0.3±0.02 and 1±0.03 μg/ml against HSV-1, HSV-2 and VZV respectively and 50% cytotoxicity (CC50) at 700 μg/ml. The highest antiviral effect of this fraction was obtained mainly when it was added during and post infection (p.i.) or when it was added only p.i. Also, this fraction significantly reduced the amount of infective endogenous viral particles in cells that were treated with the 80%-MeOH fraction only post viral entry into the host cells. A synergistic antiviral effect against all tested viruses was also observed when cells were treated with a combination of acyclovir (ACV) and 80%-MeOH fraction of Ec. Further study is required for the isolation and identification of the anti-virally active component/s of this fraction.

Article Details

Abu-Jafar, A., & Huleihel, M. (2017). Antiviral activity of Eucalyptus camaldulensis leaves ethanolic extract on herpes viruses infection. International Journal of Clinical Virology, 1(1), 001–009. https://doi.org/10.29328/journal.ijcv.1001001
Research Articles

Copyright (c) 2017 Abu- Jafar A, et al.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Müller V, Chávez JH, Reginatto FH, Zucolotto SM, Niero R, et al. Evaluation of antiviral activity of South American plant extracts against herpes simplex virus type 1 and rabies virus. Phytother Res. 2007; 10: 970-974. Ref: https://goo.gl/Y5BY1V

Elion GB, Furman PA, Fyfe JA, de Miranda P, Beauchamp L, et al. Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl)guanine. Proc Natl Acad Sci U S A. 1977; 12: 5716-5720. Ref: https://goo.gl/hFkJCr

Meyers JD, Wade JC, Mitchell CD, Saral R, Lietman PS, et al. Multicenter collaborative trial of intravenous acyclovir for treatment of mucocutaneous herpes simplex virus infection in the immunocompromised host. Am J Med. 1982; 73: 229-235. Ref: https://goo.gl/meF9HM

Snoeck R. Antiviral therapy of herpes simplex. Int J Antimicrob Agents. 2000; 16: 157-159. Ref: https://goo.gl/jhNJgQ

Khan MT, Atherb A, Thompson KD, Gambari R. Extracts and molecules from medicinal plants against herpes simplex viruses. Antiviral Res. 2005; 67: 107-119. Ref: https://goo.gl/37YbHC

Whitley RJ, Bernard Roizman. Herpes simplex virus infections. Lancet. 2001; 357: 1513-1518. Ref: https://goo.gl/eXTLqC

Celum C1, Wald A, Hughes J, Sanchez J, Reid S, et al. Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial. Lancet. 2008; 371: 2109-2119. Ref: https://goo.gl/jeCvWE

De Clercq E. Antiviral drugs in current clinical use. J Clin Virol. 2004; 30: 115-133. Ref: https://goo.gl/TCxt1x

Bao B1, Meng Z, Li N, Meng Z, Zhang L, et al. Design Synthesis and Antiviral Activity Studies of Schizonepetin Derivatives. Int J Mol Sci. 2013; 14: 17193-17203. Ref: https://goo.gl/PMF8sy

Fiddian AP, Brigden D, Yeo JM, Hickmott EA. Acyclovir: An update of the clinical applications of this antiherpes agent. Antiviral Res. 1984; 4: 99-117. Ref: https://goo.gl/utMMLp

Erlich KS, Mills J, Chatis P, Mertz GJ, Busch DF, et al. Acyclovir-Resistant Herpes Simplex Virus Infections in Patients with the Acquired Immunodeficiency Syndrome. N Engl J Med. 1989; 320: 293-296. Ref: https://goo.gl/c7ECYP

Oliver NM, Collins P, Van der Meer J, Van't Wout JW. Biological and biochemical characterization of clinical isolates of herpes simplex virus type 2 resistant to acyclovir. Antimicrob Agents Chemother. 1989; 33: 635-640. Ref: https://goo.gl/8XuHqe

Burrelab S, Aimeb C, Hermetb L, Ait-Arkoub Z, Aguta H, et al. Surveillance of herpes simplex virus resistance to antivirals: A 4-year survey. Antiviral Res. 2013; 100: 365-372. Ref: https://goo.gl/nVgrTt

Churqui MP, Lind L, Thörn K, Svensson A, Savolainen O, et al. Extracts of Equisetum giganteum L and Copaifera reticulate Ducke show strong antiviral activity against the sexually transmitted pathogen herpes simplex virus type 2. J Ethnopharmacol. 2017; 210: 192-197. Ref: https://goo.gl/Xb2H66

Frobert E, Burrel S, Ducastelle-Lepretre S, Billaud G, Ader F, et al. Resistance of herpes simplex viruses to acyclovir: An update from a ten-year survey in France. Antiviral Res. 2014; 111: 36-41. Ref: https://goo.gl/Az5DkS

Field AK, Biron KK. "The end of innocence" revisited: resistance of herpesviruses to antiviral drugs. Clin Microbiol Rev. 1994; 7: 1-13. Ref: https://goo.gl/VD1Hy2

İlker Devrim, Hasan Tezer, Göknur Haliloğlu, Ateş Kara, Gülten Seçmeer. Relapsing Herpes simplex virus encephalitis despite high-dose acyclovir therapy: a case report. Turk J Pediatr. 2008; 50: 380-382. Ref: https://goo.gl/Q429CT

Picton SF, Flatt PR, McClenaghan NH. Differential Acute and Long Term Actions of Succinic Acid Monomethyl Ester Exposure on Insulin-Secreting BRIN-BD11 Cells. Int J Exp Diabetes Res. 2001; 2: 19-27. Ref: https://goo.gl/vFehUS

Clark A . Natural products as a resource for new drugs. Pharm Res. 1996; 13: 1133-1141. Ref: https://goo.gl/4tiws9

Bailly C1, Perrine D, Lancelot JC, Saturnino C, Robba M, et al. Sequence-selective binding to DNA of bis(amidinophenoxy)alkanes related to propamidine and pentamidine. Biochem J. 1997; 323: 23-31. Ref: https://goo.gl/zuuDNz

Yarmolinsky L, Zaccai M, Ben-Shabat S, Mills D, Huleihel M. Antiviral activity of ethanol extracts of Ficus binjamina and Lilium candidum in vitro. N Biotechnol. 2009; 26: 307-313. Ref: https://goo.gl/cJA2zf

Yarmolinsky L, Huleihel M, Zaccai M, Ben-Shabat S. Potent antiviral flavone glycosides from Ficus benjamina leaves. Fitoterapia. 2012; 83: 362-367. Ref: https://goo.gl/zecCdJ

Chiang LC, Cheng HY, Liu MC, Chiang W, Lin CC. In Vitro anti-herpes simplex viruses and anti-adenoviruses activity of twelve traditionally used medicinal plants in Taiwan. Biol Pharm Bull. 2003; 26: 1600-1604. Ref: https://goo.gl/aZGTbE

Jassim SA, Naji MA. Novel antiviral agents: a medicinal plant perspective. J Appl Microbiol. 2003; 95: 412-427. Ref: https://goo.gl/3gLiUo

Sanchez Palomino S, Abad MJ, Bedoya LM, García J, Gonzales E, et al. Screening of South American Plants against Human Immunodeficiency Virus: Preliminary Fractionation of Aqueous Extract from Baccharis trinervis. Biol Pharm Bull. 2002; 25: 1147-1150. Ref: https://goo.gl/QXee6r

Elaissi A, Rouis Z, Salem NA, Mabrouk S, ben Salem Y, et al. Chemical composition of 8 eucalyptus species' essential oils and the evaluation of their antibacterial, antifungal and antiviral activities. BMC Complement Altern Med. 2012; 12: 81-81. Ref: https://goo.gl/7bTF4H

Gemechu A, Giday M, Worku A, Ameni G. In vitro Anti-mycobacterial activity of selected medicinal plants against Mycobacterium tuberculosis and Mycobacterium bovis Strains. BMC Complement Altern Med. 2013; 13: 291-291. Ref: https://goo.gl/kcmWeU

Almeida IF, Fernandes E, Lima JL, Valentão P, Andrade PB, et al. Oxygen and Nitrogen Reactive Species Are Effectively Scavenged by Eucalyptus globulus Leaf Water Extract. J Med Food. 2009; 12: 175-183. Ref: https://goo.gl/S8AWVa

Takasaki M, Konoshima T, Fujitani K, Yoshida S, Nishimura H, et al. Inhibitors of skin-tumor promotion. VIII. Inhibitory effects of euglobals and their related compounds on Epstein-Barr virus activation. (1). Chem Pharm Bull (Tokyo). 1990; 38: 2737-2739. Ref: https://goo.gl/xeVpFM

Brochot A, Guilbot A, Haddioui L, Roques C. Antibacterial, antifungal, and antiviral effects of three essential oil blends. Microbiologyopen. 2017; 6: e00459. Ref: https://goo.gl/SxkZDH

Dhifi W, Bellili S, Jazi S, Bahloul N, Mnif W. Essential Oils’ Chemical Characterization and Investigation of Some Biological Activities: A Critical Review. Medicines (Basel). 2016; 3: 25. Ref: https://goo.gl/7WX1ck

Döll-Boscardin PM, Sartoratto A, Sales Maia BH, Padilha de Paula J, Nakashima T, et al. In Vitro Cytotoxic Potential of Essential Oils of Eucalyptus benthamii and Its Related Terpenes on Tumor Cell Lines. Evid Based Complement Altern Med. 2012; 2012: 342652. Ref: https://goo.gl/FpGa7E

Astani A, Reichling J, Schnitzler P. Comparative Study on the Antiviral Activity of Selected Monoterpenes Derived from Essential Oils. Phytother Res. 2010; 24: 673-679. Ref: https://goo.gl/2MQqoB

Adeniyi BA, OO Ayepola, FD Adu. The antiviral activity of leaves of Eucalyptus camaldulensis (Dehn) and Eucalyptus torelliana (R. Muell). Pak J Pharm Sci. 2015; 28: 1773-1776. Ref: https://goo.gl/haPqTW

Ju HQ, Wang SY, Pei Y, Xiang YF, Li S, et al. [In vitro study on the anti-HSV-1 and HBV activities of extracts from the fruit of Eucalyptus maidenii]. Zhong Yao Cai. 2011; 34: 242-245. Ref: https://goo.gl/6XJw8E

YufangShi, Barbara S.Kornovski, RashminSavani, Eva ATurley. A rapid. multiwell colorimetric assay for chemotaxis. J Immunol Methods. 1993; 164: 149-154. Ref: https://goo.gl/FJss6e

Mahmoud Huleihel, Vladimir Ishanu, Jacov Tal, Shoshana (Malis) Arad. Antiviral effect of red microalgal polysaccharides on Herpes Simplex and Varicella zoster viruses. J Appl Phycology. 2001; 13: 127-134. Ref: https://goo.gl/MksrhV

Kirsten Geschera, Joachim Kühnb, Wali Hafezi, bAndreas Louisa, Andrea Derksen, et al. Inhibition of viral adsorption and penetration by an aqueous extract from Rhododendron ferrugineum L. as antiviral principle against herpes simplex virus type-1. Fitoterapia. 2011; 82: 408-413. Ref: https://goo.gl/u4riYt

Noam R, M Huleihel, Michele Zaccai. Stress conditions during plant growth increase the anti-herpetic properties of Lilium candidum leaf extracts and fractions. J Med Plants Res. 2015; 9: 954-961. Ref: https://goo.gl/4whu4n

Cheng HY, Lin LT, Huang HH, Yang CM, Lin CC. Yin Chen HaoTang, a Chinese prescription, inhibits both herpes simplex virus type-1 and type-2 infections in vitro. Antiviral Res. 2008; 77: 14-19. Ref: https://goo.gl/kPZ5Wq

Arena A, Bisignano G, Pavone B, Tomaino A, Bonina FP, et al. Antiviral and immunomodulatory effect of a lyophilized extract of Capparis spinosa L. buds. Phytother Res. 2008; 22: 313-317. Ref: https://goo.gl/qv7bUX

Cheng HY, Yang CM, Lin TC, Lin LT, Chiang LC, et al. Excoecarianin, Isolated from Phyllanthus urinaria Linnea, Inhibits Herpes Simplex Virus Type 2 Infection through Inactivation of Viral Particles. Evid Based Complement Alternat Med. 2011; 2011: 259103. Ref: https://goo.gl/LXreMR

Yang CM, Cheng HY, Lin TC, Chiang LC, Lin CC. Acetone, ethanol and methanol extracts of Phyllanthus urinaria inhibit HSV-2 infection in vitro. Antiviral Res. 2005; 67: 24-30. Ref: https://goo.gl/ixSvJK

Wyrwicz LS, Rychlewski L. Identification of Herpes TATT-binding protein. Antiviral Res. 2007; 75: 167-172. Ref: https://goo.gl/4Qi1kA

Field HJ, S Biswas, IT Mohammad. Herpesvirus latency and therapy--from a veterinary perspective. Antiviral Res. 2006; 71: 127-33. Ref: https://goo.gl/U3kGGg

Kesharwani A, Polachira SK, Nair R, Agarwal A, Mishra NN, et al. Anti-HSV-2 activity of Terminalia chebula Retz extract and its constituents, chebulagic and chebulinic acids. BMC Complement Altern Med. 2017; 17: 110. Ref: https://goo.gl/UTsnZZ

Gescher K, Kühn J, Lorentzen E, Hafezi W, Derksen A, et al. Proanthocyanidin-enriched extract from Myrothamnus flabellifolia Welw. exerts antiviral activity against herpes simplex virus type 1 by inhibition of viral adsorption and penetration. J Ethnopharmacol. 2011; 134: 468-474. Ref: https://goo.gl/Fe1Yc3

Jabareen A, M Huleihil, M Huleihel. Effect of Extracts of Passiflora edulis Leaves on Herpes Viruses Infection. J Virol Antivir Res. 2013; 2: 1-6. Ref: https://goo.gl/JcX4jG

Choi HJ, Song JH, Park KS, Kwon DH. Inhibitory effects of quercetin 3-rhamnoside on influenza A virus replication. Eur J Pharm Sci. 2009; 37: 329-333. Ref: https://goo.gl/1BrUuS

Mucsi I, Prágai BM. Inhibition of virus multiplication and alteration of cyclic AMP level in cell cultures by flavonoids. Experientia. 1985; 41: 930-931. Ref: https://goo.gl/GGqxUA