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Topical formulations containing Trichilia catigua extract as therapeutic options for a genital and an acyclovir-resistant strain of herpes recurrent infection

  • Biotechnology and Industrial Microbiology - Research Paper
  • Published:
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Abstract

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infect, respectively, 67% and 13% of the world population, most commonly causing mild symptoms, such as blisters/ulcers. However, severe conditions such as keratitis, encephalitis, and systemic infections may occur, generally associated with the patient’s immunological condition. Although Acyclovir® (ACV) and its analogs are the reference drugs for herpetic infections, the number of ACV-resistant HSV infections is growing exponentially. Therefore, new natural products’ bioactive compounds have been studied to develop novel effective anti-herpetics. Trichilia catigua is a plant widely used in traditional medicine, including the treatment of skin diseases and sexual infections. In our study, 16 extracts from the bark of T. catigua, obtained with different solvents and their combinations, were evaluated against HSV-1 AR and HSV-2, respectively, ACV resistance and genital strains in vitro. The extracts with the highest selectivity index were used to prepare new topical anti-herpetic formulations and confirmed in vivo. Two new topical formulations were suggested to treat cutaneous and genital herpetic recurrent lesions. The cytotoxicity and antiviral activity were tested using the MTT method. The cytotoxic (CC50) and inhibitory (IC50) concentrations of 50% and the selectivity index (SI: CC50/IC50) were determined. Tc12, Tc13, and Tc16 were added to the formulations. Infected BALB/c mice were treated for 8 days, and the severity of the herpetic lesions was analyzed daily. All CEs showed a CC50 value ranging from 143 to 400 µg/mL, except for Tc3 and Tc10. Tc12, Tc13, and Tc16 showed the best SI in the 0 h, virucidal, and adsorption inhibition assays. In the in vivo test against HSV-1 AR, the infected animals treated with creams were statistically different from the infected non-treated animals and similar to ACV-treated mice. In HSV-2-infected genitalia, similar effects were found for Tc13 and Tc16 gels. The present study demonstrated that extracts from the bark of T. catigua, traditionally used in folk medicine, are a valuable source of active compounds with anti-herpetic activity. The extracts showed a virucidal mechanism of action and prevented the initial stages of viral replication. The cutaneous and genital infections were strongly inhibited by the Tc12, Tc13, and Tc16 extracts. New topical therapeutic alternatives using Trichilia catigua extracts are suggested for patients infected with ACV-resistant strains of HSV.

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References

  1. Burn CA, Knipe DM, Herold BC (2020) Model of vaccine efficacy against HSV-2 superinfection of HSV-1 seropositive mice demonstrates protection by antibodies mediating cellular cytotoxicity. NPJ Vaccines 5:1–8. https://doi.org/10.1038/s41541-020-0184-7

    Article  CAS  Google Scholar 

  2. Kinghorn GR, Barbara Turner E, Barton IG et al (1983) Efficacy of topical acyclovir cream in first and recurrent episodes of genital herpes. Antiviral Res 3:291–301. https://doi.org/10.1016/0166-3542(83)90037-2

    Article  CAS  PubMed  Google Scholar 

  3. Van Puyvelde L, Geiser I, Pierre-Claver Rwangabo BS (1983) Rwandese herbal remedies used against Gonorrhoea. J Ethnopharmacol 8:279–286. https://doi.org/10.1016/0378-8741(83)90065-x

    Article  PubMed  Google Scholar 

  4. Arnold HJ, Gulumian M (1984) Pharmacopoeia of traditional medicine in Venda. J Ethnopharmacol 12:35–74. https://doi.org/10.1016/0378-8741(84)90086-2

    Article  CAS  PubMed  Google Scholar 

  5. Mabogo EDN (1990) The ethnobotany of the Vhavenda. University of Pretoria

    Google Scholar 

  6. Matos AP (2006) Busca de compostos inseticidas: Estudo de espécies do gênero Trichilia (Meliaceae). Universidade Federal de São Carlos

    Google Scholar 

  7. Longhini R, Klein T, Luciano Bruschi M et al (2013) Development and validation studies for determination of phenylpropanoid-substituted flavan-3-ols in semipurified extract of Trichilia catigua by high-performance liquid chromatography with photodiode array detection. J Sep Sci 36:1247–1254. https://doi.org/10.1002/jssc.201200911

    Article  CAS  PubMed  Google Scholar 

  8. de Ferreira LAQ, Marques CA (2018) Garrafadas: an analitical approach. Fitos 12:243–262. https://doi.org/10.17648/2446-4775.2018.639

    Article  Google Scholar 

  9. Bernardi ALS, Faccin-Galhardi LC, Rincão VP et al (2010) Effects of the Trichilia catigua (Catuaba/catigua) inhibit bovine herpesvirus-1 replication in cell culture. Virus Rev 15:112–113

    Google Scholar 

  10. Espada S, Faccin-Galhardi L, Rincao V et al (2015) Antiviral activity of Trichilia catigua bark extracts for herpesvirus and poliovirus. Curr Pharm Biotechnol 16:724–732. https://doi.org/10.2174/1389201016666150505125235

    Article  CAS  PubMed  Google Scholar 

  11. Faccin-Galhardi LC, Rincão VP, Nozawa CM, et al (2008) Antiviral activity of crude extract and the aqueous and acetate fractions from Trichilia catigua against poliovirus. In: XIX National Meeting of Virology - III Mercosur Meeting of Virology. Caxumba

  12. Lonni AASG (2012) Desenvolvimento e caracterização de formulação de uso tópico contendo extrato padronizado de Trichilia catigua para fins cosmético. http://repositorio.uem.br:8080/jspui/handle/1/5369. Accessed 31 May 2022

  13. Reed LJ, Muench H (1938) A simple method of estimating fifty per cent endpoints. Am J Epidemiol 27:493–497. https://doi.org/10.1093/oxfordjournals.aje.a118408

    Article  Google Scholar 

  14. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63. https://doi.org/10.1016/0022-1759(83)90303-4

    Article  CAS  PubMed  Google Scholar 

  15. Takeuchi H, Baba M, Shigeta S (1991) An application of tetrazolium (MTT) colorimetric assay for the screening of anti-herpes simplex virus compounds. J Virol Methods 33:61–71. https://doi.org/10.1016/0166-0934(91)90008-N

    Article  CAS  PubMed  Google Scholar 

  16. Brasil (2004) Guia de estabilidade de Produtos Cosméticos. Brasília

    Google Scholar 

  17. Brasil (2008) Guia de controle de qualidade de produtos cosméticos, 2nd ed. Ministério da Saúde, Agência Nacional de Vigilância Sanitária (ANVISA), Brasília

  18. Borghetti GS, Knorst MT (2006) Desenvolvimento e avaliação da estabilidade física de loções O/A contendo filtros solares. J Pharm Sci 42:531–537. https://doi.org/10.1590/S1516-93322006000400008

    Article  CAS  Google Scholar 

  19. OECD (2015) Guidelines for the testing of chemicals. Acute dermal irritation/corrosion. OECD Guidelines for the Testing of Chemicals, Section 4 Health Effects 1–8

  20. Wouk J, Celestino GG, Rodrigues BCD et al (2022) Sulfonated (1 → 6)-β-d-glucan (Lasiodiplodan): a promising candidate against the acyclovir-resistant herpes simplex virus type 1 (HSV-1) strain. Biomacromol 23:4041–4052. https://doi.org/10.1021/acs.biomac.2c00156

    Article  CAS  Google Scholar 

  21. Cardozo FTGS, Larsen IV, Carballo EV et al (2013) In vivo anti-herpes simplex virus activity of a sulfated derivative of Agaricus brasiliensis Mycelial Polysaccharide. Antimicrob Agents Chemother 57:2541–2549. https://doi.org/10.1128/AAC.02250-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Musarra-Pizzo M, Ginestra G, Smeriglio A et al (2019) The antimicrobial and antiviral activity of polyphenols from almond (Prunus dulcis L.) Skin. Nutrients 11:1–11. https://doi.org/10.3390/nu11102355

    Article  CAS  Google Scholar 

  23. Dai J, Mumper RJ (2010) Plant phenolics: extraction, analysis and their antioxidant and anticancer properties. Molecules 15:7313–7352. https://doi.org/10.3390/molecules15107313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Boeing JS, BarizãoSilva ÉOEBC et al (2014) Evaluation of solvent effect on the extraction of phenolic compounds and antioxidant capacities from the berries: application of principal component analysis. Chem Cent J 8:1–9. https://doi.org/10.1186/s13065-014-0048-1

    Article  CAS  Google Scholar 

  25. Rockenbach II, Lessa G, Rodrigues E et al (2008) Solvent influence on total polyphenol content, anthocyanins, and antioxidant activity of grape (Vitis vinifera) bagasse extracts from Tannat and Ancelota — different varieties of Vitis vinifera varieties. Food Science and Technology 28:238–244. https://doi.org/10.1590/S0101-20612008000500036

    Article  Google Scholar 

  26. Astani A, Navid MH, Schnitzler P (2014) Attachment and penetration of acyclovir-resistant herpes simplex virus are inhibited by Melissa officinalis extract. Phytother Res 28:1547–1552. https://doi.org/10.1002/ptr.5166

    Article  PubMed  Google Scholar 

  27. Vilhelmova-Ilieva NS, Galabov A, Mileva M (2020) Tannins as antiviral agents. Tannins - Structural Properties, Biological Properties and Current Knowledge 1–13. https://doi.org/10.5772/intechopen.86490

  28. Pizzolatti MG, Venson AF, Smânia Júnior A et al (2002) Two epimeric flavalignans from Trichilia catigua (Meliaceae) with antimicrobial activity. Zeitschrift fur Naturforschung - Section C J Biosci 57:483–488. https://doi.org/10.1515/znc-2002-5-614

    Article  CAS  Google Scholar 

  29. Rabelo DS, Paula JR, Bara MTF (2013) Quantificação de fenóis totais presentes nas cascas de Trichillia catigua A. Juss (Meliaceae). Revista Brasileira de Plantas Medicinais 15:230–236. https://doi.org/10.1590/S1516-05722013000200010

    Article  CAS  Google Scholar 

  30. Resende FO, Rodrigues-Filho E, Luftmann H et al (2011) Phenylpropanoid substituted flavan-3-ols from Trichilia catigua and their in vitro antioxidative activity. J Braz Chem Soc 22:2087–2093. https://doi.org/10.1590/S0103-50532011001100010

    Article  CAS  Google Scholar 

  31. Álvarez DM, Castillo E, Duarte LF et al (2020) Current antivirals and novel botanical molecules interfering with herpes simplex virus infection. Front Microbiol 11:1–19. https://doi.org/10.3389/fmicb.2020.00139

    Article  Google Scholar 

  32. Debiasi BW, Raiser AL, Dourado SHA et al (2021) Phytochemical screening of Cordia glabrata (MART.) A.DC. extracts and its potential antioxidant, photoprotective, antimicrobial and antiviral activities. Braz J Biol 83:e248083. https://doi.org/10.1590/1519-6984.248083

    Article  CAS  PubMed  Google Scholar 

  33. Li T, Peng T (2013) Traditional Chinese herbal medicine as a source of molecules with antiviral activity. Antiviral Res 97:1–9. https://doi.org/10.1016/j.antiviral.2012.10.006

    Article  CAS  PubMed  Google Scholar 

  34. Yamane H, Konno K, Sabelis M et al (2010) Comprehensive natural products II chemistry and biology. Elsevier, Oxford

  35. Abad MJ, Guerra JA, Bermejo P et al (2000) Search for antiviral activity in higher plant extracts. Phytother Res 14:604–607. https://doi.org/10.1002/1099-1573(200012)14:8%3c604::AID-PTR678%3e3.0.CO;2-L

    Article  CAS  PubMed  Google Scholar 

  36. Lin L-T, Chen T-Y, Chung C-Y et al (2011) Hydrolyzable tannins (chebulagic acid and punicalagin) target viral glycoprotein-glycosaminoglycan interactions to inhibit herpes simplex virus 1 entry and cell-to-cell spread. J Virol 85:4386–4398. https://doi.org/10.1128/jvi.01492-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Rajbhandari M, Wegner U, Jülich M et al (2001) Screening of Nepalese medicinal plants for antiviral activity. J Ethnopharmacol 74:251–255. https://doi.org/10.1016/S0378-8741(00)00374-3

    Article  CAS  PubMed  Google Scholar 

  38. Sicurella M, Sguizzato M, Mariani P, et al (2022) Natural polyphenol-containing gels against HSV-1 infection: a comparative study. Nanomaterials 12:. https://doi.org/10.3390/nano12020227

  39. Lonni AASG, Munhoz VM, Lopes GC, et al (2015) Development and characterization of multiple emulsions for controlled release of Trichilia catigua (Catuaba) extract. Pharmaceutical Development and Technology (Print) 1–10. https://doi.org/10.3109/10837450.2015.1081611

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Acknowledgements

Author Elisa Vicente Ribelato is grateful for the post-graduation scholarship granted by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Coordination for the Improvement of Higher Education Personnel, CAPES), protocol no. 88882.448103/2019-01.

Funding

Author Elisa Vicente Ribelato has received a post-graduate scholarship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Coordination for the Improvement of Higher Education Personnel CAPES), protocol number 88882.448103/2019–01.

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Authors and Affiliations

  1. Laboratório de Virologia, Departamento de Microbiologia-Centro de Ciências Biológicas, Universidade Estadual de Londrina (UEL), Londrina, Paraná, Brazil

    Elisa Vicente Ribelato, Jéssica Wouk, Gabriela Gomes Celestino, Bianca Cerqueira Dias Rodrigues, Maria Laura Goussain Darido, Mario Gabriel Lopes Barboza, Tatiana Jabor Botura, Sérgio Paulo Dejato da Rocha & Lígia C. Faccin-Galhardi

  2. Departamento de Histologia–Centro de Ciências Biológicas, Universidade Estadual de Londrina (UEL), Londrina, Paraná, Brazil

    Maylla Cardoso de Oliveira & Fábio Goulart de Andrade

  3. Departamento de Ciências Farmacêuticas–Centro de Ciências da Saúde, Universidade Estadual de Londrina (UEL), Londrina, Paraná, Brazil

    Audrey A. S. G. Lonni

  4. Laboratório de Biologia Farmacêutica, Palafito, Departamento de Farmácia, Universidade Estadual de Maringá (UEM), Maringá, Paraná, Brazil

    João Carlos Palazzo de Mello

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  1. Elisa Vicente Ribelato
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Contributions

All authors contributed to the study’s conception and design. JCPdeM and AASGL provided the plant materials. EVR, GGC, TJB, and MGLB performed the extracts’ antiviral screening tests. EVR, JW, BCDR, and MLGD performed in vivo assay. FGdeA and MCdeO performed histological analysis. SPDdaR and LCF-G conceived and supervised the study. EVR, JW, and LCF-G drafted the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Lígia C. Faccin-Galhardi.

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Ethics approval

All procedures performed in this study involving animals were in accordance with ARRIVE (Animal Research: Reporting of In Vivo Experiments) and following the National Council for the Control of Animal Experimentation (CONCEA) guidelines. The study was approved by the Bioethics Committee of the Universidade Estadual de Londrina (UEL), no. 16933.2018.50.

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The authors declare no competing interests.

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Ribelato, E.V., Wouk, J., Celestino, G.G. et al. Topical formulations containing Trichilia catigua extract as therapeutic options for a genital and an acyclovir-resistant strain of herpes recurrent infection. Braz J Microbiol 54, 1501–1511 (2023). https://doi.org/10.1007/s42770-023-01027-w

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