Contents lists available at ScienceDirect Journal of Herbal Medicine journal homepage: www.elsevier.com/locate/hermed Research paper Anti-Candida albicans bioflm activity of extracts from two selected indigenous Algerian plants: Clematis flammula and Fraxinus angustifolia Asma Ourabah a , Dina Atmani-Kilani a , Nadjet Debbache-Benaida a , Olga Kolesova b , Lila Azib a , Farah Yous a , Malika Benloukil a , Bruno Botta c , Djebbar Atmani a , Giovanna Simonetti d, * a Laboratoire de Biochimie Appliquée, Faculté des Sciences de la Nature et de la Vie, Université de Bejaia, 06000, Bejaia, Algeria b Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy c Department of Chemistry and Technology of Drugs, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy d Department of Environmental Biology, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Italy ARTICLE INFO Keywords: Candida albicans bioflm Clematis flammula Fraxinus angustifolia Plant extracts Phenolic compounds Virulence factors ABSTRACT Candida albicans bioflm is associated with high rates of morbidity and resistance to antifungals. The aim of the present study was to evaluate the anti-Candida albicans bioflm activity of some indigenous Algerian medicinal plant extracts: Clematis flammula and Fraxinus angustifolia and their infuence on the virulence factors of C. albicans. The anti-bioflm activity was determined using crystal violet assay while the cell surface hydrophobicity (CSH) was estimated in a water-hydrocarbon two-phase assay. Moreover, germ tube formation and hyphae elongation were assessed microscopically. F. angustifolia leaves and bark, as well as C. flammula leaf extracts (500 μg/mL) showed an inhibition of bioflm formation of 62.41 ± 3.88, 54.83 ± 0.98 and 36.78 ± 1.09 %, respectively, probably related to a disruption of CSH, germ tube and hyphae formation of C. albicans ATCC 10231 (p < 0.001). Phytochemical analysis revealed that the plant extracts were a rich source of phenolic compounds with the highest content found in F. angustifolia leaves (173.05 ± 0.15 mg gallic acid equivalent per gram of extract), which could explain its highest efciency against bioflm activity. Considering the results obtained, it can be concluded that the plants tested could be a promising source of drugs against muco-cutaneous infections caused by C. albicans bioflm. 1. Introduction Recent estimates by the National Institute of Health (USA) indicate that pathogenic bioflms are responsible, directly or indirectly, for over 80 % of all microbial infections (Nobile and Johnson, 2015). Candida albicans is a harmless commensal that lives in harmony with other members of the microbiota (Calderone and Fonzi, 2001). However, disturbances in this delicate balance would enable C. albicans to rapidly proliferate and cause infections in the form of bioflms on abiotic or biotic surfaces (Harriott et al., 2010; Ganguly and Mitchell, 2011; Mayer et al., 2013). Bioflm formation occurs in a sequential process, in which adhesion is the frst step. Adherence to epithelial and endothelial tissues as well as to abiotic surfaces depends highly on the hydrophobicty of cells (Borecká-Melkusová and Bujdáková, 2008). The second important step in bioflm formation is germ tubes formation and hyphal elongation (Yang, 2003). The last step is intrinsic to the accumulation of extracellular matrix material and dispersion of yeast cells from the bioflm complex (Harriott et al., 2010). Candida bioflm cells are much more resistant to antifungal drugs than the cells growing in planktonic form (Majumdar et al., 2016). In fact, most of the drugs currently used are not efcient against Candida bioflms (Nobile and Johnson, 2015); therefore, the search for new active compounds is highly recommended. Indeed, the discovery of a novel agent with improved tolerability and efcacy would represent an important advancement in the management of Candida diseases. In this context, recent interest in the biological activities of natural products against Candida bioflm has grown rapidly (Elisabeth et al., 2016; Liu et al., 2017; Bassyouni et al., 2018). Historically, plant extracts and their bioactive constituents remain a valuable source of natural products, which have played a central role in the prevention and treatment of diseases, thus helping to maintain human health (Beloued, 1998; Ji et al., 2009). Many medicinal plants have been explored for their anti-Candida activities (Motsei et al., 2003; https://doi.org/10.1016/j.hermed.2019.100319 Received 15 November 2018; Received in revised form 27 June 2019; Accepted 25 November 2019 ⁎ Corresponding author. E-mail address: giovanna.simonetti@uniroma1.it (G. Simonetti). Journal of Herbal Medicine 20 (2020) 100319 Available online 26 November 2019 2210-8033/ © 2019 Elsevier GmbH. All rights reserved. T