In vitro safety assessment of the strawberry tree (Arbutus unedo L.) water leaf extract and arbutin in human peripheral blood lymphocytes
- 247 Downloads
Strawberry tree (Arbutus unedo L.) leaves have long been used in the traditional medicine of the Mediterranean region. One of their most bioactive constituents is the glycoside arbutin, whose presence makes A. unedo suitable as a potential substitute for bearberry [Arctostaphylos uva ursi (L.) Spreng] leaves, an herbal preparation widely used for treating urinary tract infections. The safety and biocompatibility of strawberry tree water leaf extract have not yet been documented well. This study estimated arbutin content in strawberry tree water leaf extract (STE) using high performance liquid chromatography. Furthermore, we performed an in vitro safety assessment of the 24 h exposure to three presumably non-toxic concentrations of standardized STE and arbutin in human peripheral blood lymphocytes using the apoptosis/necrosis assay, the alkaline comet assay, and the cytokinesis-block micronucleus cytome assay. The STE was also tested for total antioxidant capacity and lipid peroxidation. At a concentration corresponding to the maximum allowable daily intake of arbutin, the tested extract was not cytotoxic, had a negligible potential for causing primary DNA damage and even hindered micronuclei formation in lymphocytes. It also showed a valuable antioxidant capacity, and did not exert marked lipid peroxidation. These promising results represent a solid frame for further development of STE-based herbal preparations. Although arbutin generally had a low DNA damaging potential, the slowing down of lymphocyte proliferation observed after 24 h of exposure points to a cytostatic effect, which merits further research.
KeywordsApoptosis Arbutus unedo L. Cytokinesis-block micronucleus “cytome” assay Oxidative stress Primary DNA damage
This study was financially supported by the Mali Lošinj Tourist Board and Institutional funding provided by the Ministry of Science and Education of the Republic of Croatia.
Compliance with ethical standards
Conflict of interest
The authors declare no conflicts of interest.
- Aydin S, Tokaç D, Başaran N, Başaran AA (2015) Effect of epigallocatechin gallate on oxidative DNA damage in human lymphocytes. Turk J Pharm Sci 12:19–28Google Scholar
- Dong Q, Zhang CJ, Zhou HB, Zou ZX, Yang GD (2005) The study of arbutin against the damage caused by a H2O2 in ECV-304 cells. J Harbin Med Univ 2:142–144. https://doi.org/10.3969/j.issn.1000-1905.2005.02.013 CrossRefGoogle Scholar
- Duke RC, Cohen JJ (1992) Morphological and biochemical assays of apoptosis. In: Coligan JE, Kruisbeal AM, Margulies DH, Shevach EM, Strober W (eds) Current protocols in immunology. Willey, New York, pp 3.17.1–3.17.16Google Scholar
- European Medicines Agency (2012) Assessment report on Arctostaphylos uva-ursi (L.) Spreng., folium. http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_HMPC_assessment_report/2011/07/WC500108750.pdf. Accessed 21 Mar 2018
- Gašić U, Jurica K, Brčić Karačonji I, Milojković Opsenica D (2015) Phytochemical fingerprint of the strawberry tree. In Todorović T, Opsenica I, Dekanski A (eds) Book of abstracts/third conference of young chemists of Serbia, Belgrade, Serbia. Serbian Chemical Society, Belgrade, Serbia, pp 11–11. ISBN: 978-86-7132-059-7Google Scholar
- Hertzog DI, Tica OA (2012) Molecular mechanisms underlying the anti-cancerous action of flavonoids. Curr Health Sci J 38:145–149Google Scholar
- Jurica K (2016) Phenolic compounds in strawberry tree (Arbutus unedo L.) and their biological effect. Doctoral thesis, Faculty of Science, University of Zagreb, Croatia, 161 ppGoogle Scholar
- NTP—National Toxicology Program (2006) Chemical information review document for arbutin [CAS No. 497-76-7] and extracts from Arctostaphylos uva-ursi. Natl Toxicol Progr pp 1–38. https://ntp.niehs.nih.gov/ntp/htdocs/chem_background/exsumpdf/arbutin_508.pdf. Accessed 1 Oct 2017
- Oliveira I, Baptista P, Bento A, Pereira JA (2011) Arbutus unedo L. and its benefits on human health. J Food Nutr Res 50:73–85Google Scholar
- Seyfizadeh N, Mahjoub S, Zabihi E, Moghadamnia A, Pouramir M, Mir H, Khosravifarsani M, Elahimanesh F (2012) Cytoprotective effects of arbutin against tert-butyl hydroperoxide induced toxicity in Hep-G2 cell line. World Appl Sci J 19:163–167Google Scholar
- Sreejaya SB, Archana D, Santhy KS (2017) Genoprotective effects of Acorus calamus rhizome against DNA damage in peripheral blood lymphocytes. Int J Green Pharm Suppl 11:S108–S111Google Scholar
- Valencia-Quintana R, Gómez-Arroyo S, Sánchez-Alarcón S, Milić M, Olivares JLG, Waliszewski SM, Cortés-Eslava J, Villalobos-Pietrini R, Calderón-Segura ME (2016a) Assessment of genotoxicity of Lannate-90® and its plant and animal metabolites in human lymphocyte cultures. Arh Hig Rada Toksikol 67:116–125CrossRefPubMedGoogle Scholar
- Valencia-Quintana R, Gómez-Arroyo S, Sánchez-Alarcón S, Milić M, Olivares JLG, Waliszewski SM, Cortés-Eslava J, Villalobos-Pietrini R, Calderón-Segura ME (2016b) Genotoxic effects of the carbamate insecticide Pirimor-50® in Vicia faba root tip meristems and human lymphocyte culture after direct application and treatment with its metabolic extracts. Arh Hig Rada Toksikol 67:266–276CrossRefPubMedGoogle Scholar