Otilia Bobiş
Andresa Aparecida Berretta
Miguel Vilas-Boas
David De Jong- 1Faculty of Animal Science and Biotechnology, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, Cluj-Napoca, Romania
- 2Research Development and Innovation Department, Apis Flora Indl Coml Ltd., Ribeirão Preto, Brazil
- 3Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Bragança, Portugal
- 4Ribeirão Preto Medical School, University of São Paulo (FMRP/USP), Ribeirão Preto, Brazil
Editorial on the Research Topic
Therapeutic potential of propolis—from in vitro studies to clinical trials
Propolis is a natural product made by bees from bioactive plant exudates and/or resins, which they employ to protect their colony health and integrity (Ghisalberti, 1979; Simone-Finstrom and Spivak, 2010). Taking their cue from the bees, man has been harvesting and using this product for thousands of years, across many civilizations, stimulated by empirical knowledge concerning its efficacy as a medically useful product (Berretta et al., 2020). More recently, the development of analytical methods and modern extraction processes has led to numerous studies regarding the chemical composition and diversity of propolis, and to a better understanding of its therapeutic properties (Bankova et al., 2019). There are numerous scientific publications showing the antimicrobial, antifungal, antiviral, anti-inflammatory, immunoregulatory, and other biological properties of propolis, especially in vitro and animal models (Machado et al., 2012; Berretta et al., 2013; Hori et al., 2013; Salatino, 2022). Based on observations from traditional medicine uses of propolis, well-conducted pre-clinical and clinical studies have investigated the therapeutic benefits of propolis for treating a multitude of diseases (Silveira et al., 2019; Berretta et al., 2020; Diniz et al., 2020; Gonçalves et al., 2021; Salatino, 2022). However, routine use of propolis as a health aid requires special care and attention due to the difficulty of guaranteeing a uniform chemical composition, considering that it varies according to plant sources and regions where it is produced (Bankova, 2005; Berretta et al., 2012; Salatino, 2022). Other factors that can affect its properties include the extraction solvents and processes used to produce propolis extracts (Galeotti et al., 2018; Bankova et al., 2021; Suran et al., 2021); these are aspects that potentially also impact their safety and efficacy.
Along this line, the main objective of this Research Topic in Frontiers in Pharmacology was to increase our understanding of how propolis will function in clinical settings, focusing on recent progress in propolis research, to provide an overview of the state of the art in this field. There is considerable evidence that propolis can be therapeutically beneficial, and in vitro, in vivo, and clinical studies motivated by such evidence have frequently confirmed its utility (Berretta et al., 2020; Salatino, 2022). The continuous use of synthetic medications has resulted in pathogenic bacteria and viruses becoming resistant to these molecules (Salatino, 2022). Consequently, finding alternative options for treatment has become a priority. The various bee products have been intensely studied; among these propolis and its components, with their known properties, have become the principal focus for health research (Salatino, 2022). To help fully understand the potential role of propolis as a health product, pharmacological studies should be encouraged in order to objectively examine the safety and therapeutic benefits of propolis for various diseases and pathologies.
A review paper regarding the suitability of propolis as a bioactive component of biomaterials was included in this Research Topic (Lesmana et al.). This is an innovative approach, since propolis is known mainly as an ingredient in medicinal formulations. This review article analyzes the potential application of propolis as a biomaterial component that can be mixed with other natural or synthetic materials. In the case of orthopedic/dentistry-related materials, two important aspects need to be taken into consideration: osseointegration and protection against infection. Due to the immunomodulatory and anti-inflammatory properties of propolis, it can be considered a useful candidate as a component in biomaterials used in dentistry, including titanium-based biomaterials. Another field in which biomaterials must have certain specific properties is orthopedic applications that use hydroxyapatite/calcium phosphate-based biomaterials. Skin dressing biomaterials used in wound management are important challenges for medicine because mortality from chronic wounds is comparable to that of cancer. The inclusion of propolis in polyvinyl alcohol fiber mats demonstrated that its bioactive compounds were released to the wound. Their healing effects were improved by incorporating silver nanoparticles and propolis into the fiber mats.
Two original research articles (Gonçalves et al.; Rebouças-Silva et al.) were also published in this Research Topic, describing several bioactive properties of propolis (leishmanicidal, immunomodulatory, and cardioprotective). Gonçalves et al. investigated the effects of standardized green propolis extract on heart outcomes of Parkinson rats, through PET imaging to assess cardiac 2-Deoxy-2-18F-fluoro-d-glucose uptake, and by metabolomics to examine the metabolic response to dietary propolis supplementation. The observations include evidence that Brazilian standardized green propolis extract increases cardiac glucose metabolism in propolis-fed rats and showed the relevant metabolic pathways involved in the underlying alterations in metabolite abundance. Propolis supplementation is suggested as a potential treatment to minimize non-motor manifestations of Parkinson’s disease.
Leishmaniasis is part of a group of vector-borne tropical diseases with serious therapeutic limitations. In the study by Rebouças-Silva et al., Brazilian propolis as a standardized product (EPP-AF®) alone and incorporated into a gel formulation was evaluated as an anti-leishmanicidal agent and as an immunomodulator. In vitro studies showed that EPP-AF® reduced macrophage infection and modulated the production of various inflammatory biomarkers. In vivo analysis demonstrated the effectiveness of a gel formulation containing EPP-AF® for reducing lesion size in infected mice (cutaneous Leishmaniasis).
A clinical trial was also published (Fernandez et al.), in which Brazilian organic propolis extract was used for the treatment of patients after radiotherapy, applied following surgery of head and neck cancer. The use of radiotherapy procedures in oral and oropharyngeal cancer patients can induce acute and chronic toxicities, including oral mucositis, dysphagia, dysgeusia, and oral candidiasis. Finding natural remedies as complementary therapeutics after radiotherapy could help reduce the impact of these side effects on the patients. Organic Brazilian propolis has shown considerable antioxidant, anti-inflammatory and antifungal properties and was used as a complementary therapeutic option for radiotherapy-induced toxicity. Randomized patients received?? an aqueous suspension of propolis or a placebo. Propolis lowered the mean score of toxicity after radiotherapy, and reduced patient pain. Oral candidiasis was also reduced. In conclusion, the topical use of aqueous propolis extract was useful as a complementary option for the prevention and treatment of toxicities resulting from radiotherapy of head and neck cancer patients.
Overall, the published articles in this Research Topic covered various novel and relevant aspects of the therapeutic potential of propolis, portraying new findings that will help strengthen the development of medicinal applications of propolis and its inclusion in clinical practice. We hope that this series of publications will stimulate further studies to improve knowledge in this challenging field.
Author contributions
All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.
Acknowledgments
The editors would like to express their gratitude to the authors of the publications in this Research Topic for choosing this edition to display their work and to Frontiers in Pharmacology for launching this Propolis Research Topic.
Conflict of interest
Author AB was employed by the company Apis Flora Indl Coml Ltd.
The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
References
Bankova, V., Bertelli, D., Borba, R., Conti, B. J., Cunha, I. B. S., Danert, C., et al. (2019). Standard methods for Apis mellifera propolis research. J. Apic. Res. J. Apic. Res. 58 (2), 1–49. doi:10.1080/00218839.2016.1222661
Bankova, V. (2005). Recent trends and important developments in propolis research. Evid. Based. Complement. Altern. Med. 2, 29–32. doi:10.1093/ecam/neh059
Bankova, V., Trusheva, B., and Popova, M. (2021). Propolis extraction methods: A review. J. Apic. Res. 60, 734–743. doi:10.1080/00218839.2021.1901426
Berretta, A. A., Castro, P. A., Cavalheiro, A. H., Fortes, V. S., Bom, V. P., Nascimento, A. P., et al. (2013). Evaluation of mucoadhesive gels with propolis (EPP-AF) in preclinical treatment of candidiasis vulvo vaginal infection. Evid. Based Complement. Altern. Med. 2013, 641480. doi:10.1155/2013/641480
Berretta, A. A., Nascimento, A. P., Bueno, P. C. P., Vaz, M. M. O. L. L., and Marchetti, J. M. (2012). Propolis standardized extract (EPP-AF®), an innovative chemically and biologically reproducible pharmaceutical compound for treating wounds. Int. J. Biol. Sci. 8, 512–521. doi:10.7150/ijbs.3641
Berretta, A. A., Silveira, M. A. D., Capcha, J. M. C., and De Jong, D. (2020). Propolis and its potential against SARS-CoV-2 infection mechanisms and COVID-19 disease Running title: Propolis against SARS-CoV-2 infection and COVID-19. Biomed. Pharmacother. 131, 110622. doi:10.1016/j.biopha.2020.110622
Diniz, D. P., Lorencini, D. A., Berretta, A. A., Cintra, M. A. C. T., Lia, E. N., Jordão, A. A., et al. (2020). Antioxidant effect of standardized extract of propolis (EPP-AF®) in healthy volunteers: A “before and after” clinical study. Evid. Based Complement. Altern. Med. 2020, 7538232. doi:10.1155/2020/7538232
Galeotti, F., Maccari, F., Fachini, A., and Volpi, N. (2018). Chemical composition and antioxidant activity of propolis prepared in different forms and in different solvents useful for finished products. Foods 7, 41. doi:10.3390/foods7030041
Ghisalberti, E. L. (1979). Propolis: A review. Bee World 60 (2), 59–84. doi:10.1080/0005772X.1979.11097738
Gonçalves, J. M. M., Ribeiro, C. F., and Berretta, A. A. (2021). Acupuncture, yoga, homeopathy, and apitherapy under the vibrational point of view, alternative medicine - update. IntechOpen 27. doi:10.5772/intechopen.94997
Hori, J. I., Zamboni, D. S., Carrão, D. B., Goldman, G. H., and Berretta, A. A. (2013) The inhibition of inflammasome by Brazilian propolis (EPP-AF). Evid. Based Complement. Altern. Med. 2013, 418508. doi:10.1155/2013/418508
Machado, J. L., Assunção, A. K. M., Silva, M. C. P., Reis, A. S., Costa, G. C., Arruda, D. S., et al. (2012). Brazilian green propolis: Anti-inflammatory property by an immunomodulatory activity. Evid. Based Complement. Altern. Med. 2012, 157652. doi:10.1155/2012/157652
Salatino, A. (2022). Perspectives for uses of propolis in therapy against infectious diseases. Molecules 27, 4594. doi:10.3390/molecules27144594
Silveira, M. A. D., Teles, F., Berretta, A. A., Sanches, T. R., Rodrigues, C. E., Seguro, A. C., et al. (2019). Effects of Brazilian green propolis on proteinuria and renal function in patients with chronic kidney disease: A randomized, double-blind, placebo-controlled trial. BMC Nephrol. 20, 140. doi:10.1186/s12882-019-1337-7
Simone-Finstrom, M., and Spivak, M. (2010). Propolis and bee health: The natural history and significance of resin use by honey bees. Apidologie 41, 295–311. doi:10.1051/apido/2010016
Keywords: bioactive component, propolis, properties, therapeutic potential, editorial
Citation: Bobiş O, Berretta AA, Vilas-Boas M and De Jong D (2023) Editorial: Therapeutic potential of propolis—from in vitro studies to clinical trials. Front. Pharmacol. 14:1192045. doi: 10.3389/fphar.2023.1192045
Received: 22 March 2023; Accepted: 18 April 2023;
Published: 25 May 2023.
Edited by:
Javier Echeverria, University of Santiago, ChileReviewed by:
Dâmaris Silveira, University of Brasilia, BrazilCopyright © 2023 Bobiş, Berretta, Vilas-Boas and De Jong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Otilia Bobiş, obobis@usamvcluj.ro; Andresa Aparecida Berretta, andresa.berretta@apisflora.com.br