Skip to main content

Advertisement

Log in

Combination effect of three anti-HSV-2 active plant extracts exhibiting different modes of action

  • Research Article
  • Published:
Advances in Traditional Medicine Aims and scope Submit manuscript

Abstract

The emergence of multidrug-resistant viruses leads to discover a novel source of drugs or a new strategy to overcome this obstacle. Combined herbal therapies are becoming a promising approach for a better efficiency. In this study, Pistacia lentiscus and Peganum harmala were investigated for their anti HSV-2 activity. Twenty eight organic extracts from different organs were evaluated for their cytotoxicity on Vero cells and their anti HSV-2 activity using the MTT test and the plaque reduction assay, respectively. Peganum harmala methanol seeds extract, Pistacia lentiscus methanol stem and dichloromethane fruit extracts were active on HSV-2 with selectivity index values of 13.19, 51.23 and 10.23, respectively. These active extracts exhibited different mode of action: (1) Peganum harmala methanol seeds extract showed a virucidal action before virus adsorption and penetration, and on the newly formed virions before their release outside infected cells—(2) Pistacia lentiscus methanol stem extract exhibited virucidal effect only before virus adsorption and penetration—(3) Pistacia lentiscus dichloromethane fruit extracts demonstrated virus inhibition up to 7 h post infection. The binary combination of the three active extracts did not improve their individually activity. This report could contribute to prove that combination of active extracts do not necessary increase the initial activity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  • Ali-Shtayeh MS, Yaghmour RM, Faidi YR, Salem K, Al-Nuri MA (1998) Antimicrobial activity of 20 plants used in folkloric medicine in the Palestinian area. J Ethnopharmacol 60:265–271

    Article  CAS  Google Scholar 

  • Ali-Shtayeh MS, Yaniv Z, Mahajna J (2000) Ethnobotanical survey in the Palestinian area: a classification of the healing potential of medicinal plants. J Ethnopharmacol 73:221–223

    Article  CAS  Google Scholar 

  • Asgarpanah J, Ramezanloo F (2012) Chemistry, pharmacology and medicinal properties of Peganum harmala L. Afr J Pharm Pharmacol 6:1573–1580

    CAS  Google Scholar 

  • Bentley RY, Trimen H (1980) Medicinal plants. Churchill, London, p 68

    Google Scholar 

  • Bergmann JS, Woods GL (1998) In vitro activity of antimicrobial combinations against clinical isolates of susceptible and resistant Mycobacterium tuberculosis. Int J Tuberc Lung Dis 2:621–626

    CAS  PubMed  Google Scholar 

  • Cheng HY, Yang CM, Lin TC, Lin LT, Chiang LC (2011) Lin CC (2011) Excoecarianin, isolated from Phyllanthus urinaria Linnea, inhibits herpes simplex virus type 2 infection through inactivation of viral particles. Evid Based Complement Altern Med 2011(1741-427X):259103

    Google Scholar 

  • Delaney WE, Yang H, Miller MD, Gibbs CS, Xiong S (2004) Combinations of adefovir with nucleoside analogs produce additive antiviral effects against hepatitis B virus in vitro. Antimicrob Agents Chemother 48:3702–3710

    Article  CAS  Google Scholar 

  • Dimas K, Hatziantoniou S, Wyche JH, Pantazis P (2009) A mastic gum extract induces supression of growth of human colorectal tumor xenografts in immunodeficient mice. Vivo 23:63–68

    CAS  Google Scholar 

  • Hayashi K, Hayashi T, Kojima I (1996) A natural sulfated polysaccharide, calcium spirulan, isolated from Spirulina platensis: in vitro and ex vivo evaluation of anti-herpes simplex virus and anti-human immunodeficiency virus activities. AIDS Res Hum Retroviruses 12:1463–1471

    Article  CAS  Google Scholar 

  • Herrick TM, Million RP (2007) Tapping the potential of fixed dose combinations. Nat Rev Drug Discov 6:513–514

    Article  CAS  Google Scholar 

  • Hook EW, Cannon RO, Nahmias AJ, Lee FF, Campbell CHJ, Glasser D, Quinn TC (1992) Herpes simplex virus infection as a risk factor for human immunodeficiency virus infection in heterosexuals. J Infect Dis 165:251–255

    Article  Google Scholar 

  • Humphrey RW, Brockway-Lunardi LM, Bonk DT, Dohoney KM, Doroshow JH, Meech SJ (2011) Opportunities and challenges in the development of experimental drug combinations for cancer. J Nat Cancer Inst 103:1222–1226

    Article  CAS  Google Scholar 

  • Kiani SJ, Shamsi Shahrabadi M, Ataei A, Sajjadi N (2007) Peganum harmala seed extract can prevent HSV-1 replication in vitro. Iran J Virol 1:11–16

    Article  Google Scholar 

  • Lapucci A, Macchia M, Parkin A (1993) Antiherpes virus agents: a review. Farmaco 48:871–895

    CAS  PubMed  Google Scholar 

  • Larder BA, Kemp SD, Harrigan PR (1995) Potential mechanism for sustained antiretroviral efficacy of AZT-3TC combination therapy. Science 269:696–699

    Article  CAS  Google Scholar 

  • Larson EC, Hathaway LB, Lamb JG, Pond CD, Rai PP, Matainaho TK, Piskaut P, Barrows LR, Franklin MR (2014) Interactions of Papua New Guinea medicinal plant extracts with antiretroviral therapy. J Ethnopharmacol 155:1433–1440

    Article  CAS  Google Scholar 

  • Lev E, Amar Z (2002) Ethnopharmacological survey of traditional drugs sold in the Kingdom of Jordan. J Ethnopharmacol 82:131–145

    Article  Google Scholar 

  • Levinson W, Jawetz E (2002) Medical microbiology and immunology: examination and board review, 7th edn. Lange Medical Books/McGraw-Hill, New York

    Google Scholar 

  • Liu W, Cheng X, Wang Y, Li S, Zheng T, Gao Y, Wang G, Qi S, Wang J, Ni J, Wang Z, Wang C (2015) In vivo evaluation of the antitussive, expectorant and bronchodilating effects of extract and fractions from aerial parts of Peganum harmala linn. J Ethnopharmacol 13(162):79–86

    Article  Google Scholar 

  • Monsef HR, Ghobadi A, Iranshahi M, Abdollahi M (2004) Antinociceptive effects of Peganum harmala L. alkaloid extract on mouse formalin test. J Pharm Pharm Sci 7:65–69

    CAS  PubMed  Google Scholar 

  • Moradi MT, Karimi A, Fotouhi F, Kheiri S, Torabi A (2017a) In vitro and in vivo effects of Peganum harmala L. seeds extract against influenza A virus. Avicenna J Phytomed 7:519–530

    CAS  PubMed  PubMed Central  Google Scholar 

  • Moradi MT, Karimi A, Rafieian-Kopaei M, Fotouhi F (2017b) In vitro antiviral effects of Peganum harmala seed extract and its total alkaloids against Influenza virus. Microb Pathog 110:42–49

    Article  CAS  Google Scholar 

  • Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  CAS  Google Scholar 

  • Nenaah G (2010) Antibacterial and antifungal activities of (beta)-carboline alkaloids of Peganum harmala (L) seeds and their combination effects. Fitoterapia 81:779–782

    Article  CAS  Google Scholar 

  • Patel SJ, Kuten SA, Musick WL, Gaber AO, Monsour HP, Knight RJ (2016) Combination drug products for HIV-A word of caution for the transplant clinician. Am J Transplant 16:2479–2482

    Article  CAS  Google Scholar 

  • Pellecuer J, Jacob M, Simeon DM, Dusart G, Attisto M, Barthez M, Gourgas L, Pascal B, Tomei R (1980) Essais d’utilisations d’huiles essentielles de plantes aromatiques Méditerranéennes en odontologie conservatrice. Plantes Medicinales et Phytotherapie 14:83–98

    CAS  Google Scholar 

  • Singha VK, Mishrab V, Tiwaria S, Khaliqa T, Barthwalb MK, Pandeyc HP, Palitb G, Narendera T (2013) Anti-secretory and cyto-protective effects of peganine hydrochloride isolated from the seeds of Peganum harmala on gastric ulcers. Phytomedicine 20:1180–1185

    Article  Google Scholar 

  • Sudo K, Konno K, Yokota T, Shigeta S (1994) A sensitive assay system screening antiviral compounds against herpes simplex virus type 1 and type 2. J Virol Methods 49:169–178

    Article  Google Scholar 

  • Suzuki R, Sakagami H, Amano S, Fukuchi K, Sunaga K, Kanamot T, Terakubo S, Nakashima H, Shirataki Y, Tomomura M, Masuda Y, Yokose S, Tomomura A, Watanabe H, Okawara M, Matahira Y (2017) Evaluation of biological activity of mastic extracts based on chemotherapeutic indices. Vivo 31:591–598

    Article  CAS  Google Scholar 

  • Takahashi K, Fukazawa M, Motohia H, Ochiai K, Nishikawa H, Miyata TA (2003) Pilot study on antiplaque effects of mastic chewing gum in the oral cavity. J Periodontol 74:501–505

    Article  Google Scholar 

  • Yin N, Ma W, Pei J, Ouyang Q, Tang C, Lai L (2014) synergistic and antagonistic drug combinations depend on network topology. PLoS ONE 9(4):e93960

    Article  Google Scholar 

  • Yoosook C, Bunyapraphatsara N, Boonyakiat Y, Kantasuk C (2000) Anti-herpes simplex virus activities of crude water extracts of Thai medicinal plants. Phytomedicine 6:411–419

    Article  CAS  Google Scholar 

  • Yuan R (2000) Traditional Chinese medicine an approach to scientific proof and clinical validation. Pharmacol Therapeut 86:191–198

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful to Dr. Hela KALLEL and Mrs Ahlem BEN YAHIA (Pasteur Institute of Tunis, Tunisia), for providing Vero cell line and HSV-2 clinical isolate, and Pr. Abderrazak SMAOUI (Center of Biotechnology of Borj Cedria) for his help in plant collection and their identification (Grant No.: LR15CBBC03).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Roudaina Benzekri or Lamjed Bouslama.

Ethics declarations

Ethical statement

This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

Roudaina Benzekri has no conflict of interest. Ferid Limam has no conflict of interest. Lamjed Bouslama has no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Benzekri, R., Limam, F. & Bouslama, L. Combination effect of three anti-HSV-2 active plant extracts exhibiting different modes of action. ADV TRADIT MED (ADTM) 20, 223–231 (2020). https://doi.org/10.1007/s13596-020-00430-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13596-020-00430-0

Keywords

Navigation