DOI QR코드

DOI QR Code

Pine Needle Extract Applicable to Topical Treatment for the Prevention of Human Papillomavirus Infection

  • Lee, Hee-Jung (Department of Biomedical Science and Engineering, Konkuk University) ;
  • Park, Mina (Department of Biomedical Science and Engineering, Konkuk University) ;
  • Choi, HeeJae (Department of Biomedical Science and Engineering, Konkuk University) ;
  • Nowakowska, Aleksandra (Department of Biomedical Science and Engineering, Konkuk University) ;
  • Moon, Chiung (Moonstech) ;
  • Kwak, Jong Hwan (School of Pharmacy, Sungkyunkwan University) ;
  • Kim, Young Bong (Department of Biomedical Science and Engineering, Konkuk University)
  • Received : 2020.10.27
  • Accepted : 2020.11.04
  • Published : 2021.01.28

Abstract

Most cervical cancers are associated with high-risk human papillomavirus (HPV) infection. Currently, cervical cancer treatment entails surgical removal of the lesion, but treatment of infection and preventing tissue damage are issues that still remain to be addressed. Herbal medicine and biological studies have focused on developing antiviral drugs from natural sources. In this study, we analyzed the potential antiviral effects of Pinus densiflora Sieb. et Zucc. leaf extracts against HPV. The pine needle extracts from each organic solvent were analyzed for antiviral activity. The methylene chloride fraction (PN-MC) showed the highest activity against HPV pseudovirus (PV). The PN-MC extract was more effective before, rather than after treatment, and therefore represents a prophylactic intervention. Mice were pre-treated with PN-MC via genital application or oral administration, followed by a genital or subcutaneous challenge with HPV PV, respectively. The HPV challenge results showed that mice treated via genital application exhibited complete protection against HPV. In conclusion, PN-MC represents a potential topical virucide for HPV infection.

Keywords

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68: 394-424. https://doi.org/10.3322/caac.21492
  2. Lembo D, Donalisio M, Rusnati M, Bugatti A, Cornaglia M, Cappello P, et al. 2008. Sulfated K5 Escherichia coli polysaccharide derivatives as wide-range inhibitors of genital types of human papillomavirus. Antimicrob. Agents Chemother. 52: 1374-1381. https://doi.org/10.1128/AAC.01467-07
  3. Small W, Jr., Bacon MA, Bajaj A, Chuang LT, Fisher BJ, Harkenrider MM, et al. 2017. Cervical cancer: A global health crisis. Cancer 123: 2404-2412. https://doi.org/10.1002/cncr.30667
  4. Li N, Franceschi S, Howell-Jones R, Snijders PJ, Clifford GM. 2011. Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: Variation by geographical region, histological type and year of publication. Int. J. Cancer 128: 927-935. https://doi.org/10.1002/ijc.25396
  5. Donalisio M, Rusnati M, Civra A, Bugatti A, Allemand D, Pirri G, et al. 2010. Identification of a dendrimeric heparan sulfate-binding peptide that inhibits infectivity of genital types of human papillomaviruses. Antimicrob. Agents Chemother. 54: 4290-4299. https://doi.org/10.1128/aac.00471-10
  6. Stanley MA. 2012. Genital human papillomavirus infections: current and prospective therapies. J. Gen. Virol. 93: 681-691. https://doi.org/10.1099/vir.0.039677-0
  7. Moscicki AB. 2005. Impact of HPV infection in adolescent populations. J. Adolesc. Health 37: S3-9. https://doi.org/10.1016/j.jadohealth.2005.09.011
  8. Wang SX, Zhang XS, Guan HS, Wang W. 2014. Potential anti-HPV and related cancer agents from marine resources: an overview. Mar. Drugs 12: 2019-2035. https://doi.org/10.3390/md12042019
  9. Cha MK, Lee DK, An HM, Lee SW, Shin SH, Kwon JH, et al. 2012. Antiviral activity of Bifidobacterium adolescentis SPM1005-A on human papillomavirus type 16. BMC Med. 10: 72. https://doi.org/10.1186/1741-7015-10-72
  10. Underwood MR, Shewchuk LM, Hassell AM, Phelps WC. 2000. Searching for antiviral drugs for human papillomaviruses. Antivir. Ther. 5: 229-242. https://doi.org/10.1177/135965350000500401
  11. Ahn WS, Yoo J, Huh SW, Kim CK, Lee JM, Namkoong SE, et al. 2003. Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions. Eur. J. Cancer Prev. 12: 383-390. https://doi.org/10.1097/00008469-200310000-00007
  12. Fradet-Turcotte A, Archambault J. 2007. Recent advances in the search for antiviral agents against human papillomaviruses. Antivir. Ther. 12: 431-451. https://doi.org/10.1177/135965350701200417
  13. Lee BH, Chathuranga K, Uddin MB, Weeratunga P, Kim MS, Cho WK, et al. 2017. Coptidis Rhizoma extract inhibits replication of respiratory syncytial virus in vitro and in vivo by inducing antiviral state. J. Microbiol. 55: 488-498. https://doi.org/10.1007/s12275-017-7088-x
  14. Iljazovic E, Ljuca D, Sahimpasic A, Avdic S. 2006. Efficacy in treatment of cervical HRHPV infection by combination of beta interferon, and herbal therapy in woman with different cervical lesions. Bosn. J. Basic Med. Sci. 6: 79-84. https://doi.org/10.17305/bjbms.2006.3128
  15. Polansky H, Itzkovitz E, Javaherian A. 2017. Human papillomavirus (HPV): systemic treatment with Gene-Eden-VIR/Novirin safely and effectively clears virus. Drug Des. Devel. Ther. 11: 575-583. https://doi.org/10.2147/DDDT.S123340
  16. Miyoshi N, Tanabe H, Suzuki T, Saeki K, Hara Y. 2020. Applications of a standardized green tea catechin preparation for viral warts and human papilloma virus-related and unrelated cancers. Molecules 25: 2588. https://doi.org/10.3390/molecules25112588
  17. Ha TKQ, Lee BW, Nguyen NH, Cho HM, Venkatesan T, Doan TP, et al. 2020. Antiviral activities of compounds isolated from pinus densiflora (Pine Tree) against the influenza A Virus. Biomolecule 10: 711. https://doi.org/10.3390/biom10050711
  18. Zou K, Zhao Y, Tu G, Cui J, Jia Z, Zhang R. 2000. Two diastereomeric saponins with cytotoxic activity from Albizia julibrissin. Carbohydr. Res. 324: 182-188. https://doi.org/10.1016/S0008-6215(99)00294-3
  19. Buck CB, Pastrana DV, Lowy DR, Schiller JT. 2004. Efficient intracellular assembly of papillomaviral vectors. J. Virol. 78: 751-757. https://doi.org/10.1128/JVI.78.2.751-757.2004
  20. Pastrana DV, Buck CB, Pang YY, Thompson CD, Castle PE, FitzGerald PC, et al. 2004. Reactivity of human sera in a sensitive, highthroughput pseudovirus-based papillomavirus neutralization assay for HPV16 and HPV18. Virology 321: 205-216. https://doi.org/10.1016/j.virol.2003.12.027
  21. Buck CB, Cheng N, Thompson CD, Lowy DR, Steven AC, Schiller JT, et al. 2008. Arrangement of L2 within the papillomavirus capsid. J. Virol. 82: 5190-5197. https://doi.org/10.1128/JVI.02726-07
  22. Buck CB, Thompson CD. 2007. Production of papillomavirus-based gene transfer vectors. Curr. Protoc. Cell Biol. Chapter 26: Unit 26.1.
  23. Johnson KM, Kines RC, Roberts JN, Lowy DR, Schiller JT, Day PM. 2009. Role of heparan sulfate in attachment to and infection of the murine female genital tract by human papillomavirus. J. Virol. 83: 2067-2074. https://doi.org/10.1128/JVI.02190-08
  24. Buck CB, Thompson CD, Pang YY, Lowy DR, Schiller JT. 2005. Maturation of papillomavirus capsids. J. Virol. 79: 2839-2846. https://doi.org/10.1128/JVI.79.5.2839-2846.2005
  25. Conway MJ, Alam S, Ryndock EJ, Cruz L, Christensen ND, Roden RB, et al. 2009. Tissue-spanning redox gradient-dependent assembly of native human papillomavirus type 16 virions. J. Virol. 83: 10515-10526. https://doi.org/10.1128/JVI.00731-09
  26. Lee HJ, Hur YK, Cho YD, Kim MG, Lee HT, Oh YK, et al. 2012. Immunogenicity of bivalent human papillomavirus DNA vaccine using human endogenous retrovirus envelope-coated baculoviral vectors in mice and pigs. PLoS One 7: e50296. https://doi.org/10.1371/journal.pone.0050296
  27. Roberts JN, Buck CB, Thompson CD, Kines R, Bernardo M, Choyke PL, et al. 2007. Genital transmission of HPV in a mouse model is potentiated by nonoxynol-9 and inhibited by carrageenan. Nat. Med. 13: 857-861. https://doi.org/10.1038/nm1598
  28. Longet S, Schiller JT, Bobst M, Jichlinski P, Nardelli-Haefliger D. 2011. A murine genital-challenge model is a sensitive measure of protective antibodies against human papillomavirus infection. J. Virol. 85: 13253-13259. https://doi.org/10.1128/JVI.06093-11
  29. Singh O, Garg T, Rath G, Goyal AK. 2014. Microbicides for the treatment of sexually transmitted HIV Infections. J. Pharm. (Cairo). 2014: 352425. https://doi.org/10.1155/2014/352425
  30. Calagna G, Maranto M, Paola C, Capra G, Perino A, Chiantera V, et al. 2020. 'Secondary prevention' against female HPV infection: literature review of the role of carrageenan. Expert Rev. Anti. Infect. Ther. 18: 865-874. https://doi.org/10.1080/14787210.2020.1770082
  31. Lee C. 2020. Carrageenans as broad-spectrum microbicides: currentstatus and challenges. Mar. Drugs 18: 435. https://doi.org/10.3390/md18090435