Periodontal disease and caries are highly prevalent oral health problems and the main causes of tooth loss. They impact the quality of life and self-esteem of the affected patients and contribute to the development of chronic diseases (Chapple et al., 2017, Petersen and Ogawa, 2012). Periodontal disease and caries depend on biofilm formation, have multifactorial origin, and involve several bacteria. For example, Actinomyces naeslundii, Porphyromonas gingivalis, Streptococcus sanguinis, S. oralis, S. intermedius, S. gordonii, Fusobacterium nucleatum, and Tannerella forsythia (Hong et al., 2015) underlie the start and progress of periodontitis, whereas S. mutans, S. sobrinus, Lactobacillus salivarius, L. paracasei, and Bifidobacterium dentium are related to caries initiation and formation (Selwitz, Ismail, & Pitts, 2007; Henne, Rheinberg, Melzer-Krick & Conrads, 2015; Sanz et al., 2017). Some of these microorganisms are also related to non-odontogenic infections, such as pulmonary actinomycosis (Huang et al., 2021), bacterial endocarditis (Holland et al., 2016, Nomura et al., 2013), and cancer-related events including breast tumor progression and growth (Parhi et al., 2020) and increased predisposition to head and neck cancer (Bronzato et al., 2020, Malinowski et al., 2019).

Preventing periodontal disease and caries consists in daily removing biofilm from teeth through mechanical and chemical methods. The former method is considered the most effective and consists in associating flossing with toothbrushing (Figuero et al., 2017). The chemical method complements the mechanical method and is based on the antiseptic action conferred by its active principles (chlorhexidine gluconate, triclosan, and cetylpyridinium), which effectively reduce bacterial plaque. However, controlling plaque through the chemical method for a long time can cause an imbalance in the host’s microbiota, which culminates in mouth sores, decreased salivary flow, tooth staining, and taste changes (Bedoux et al., 2012, Gunsolley, 2010; Riley & Lamont, 2013; James et al., 2017; Da Costa et al., 2017). To avoid the side effects of chemical agents and to aid periodontal disease and caries prevention and treatment, researchers have studied the use of medicinal plants in oral health (Khalid et al., 2017, Tanideh et al., 2019).

Numerous plants have been employed as sources of products with nutritional and therapeutic values, particularly in Africa. One example is Euclea natalensis A.D.C., popularly known as “Mulala”, which belongs to the family Ebenaceae and is common in tropical and subtropical regions of Africa (Lall et al., 2016). Euclea natalensis roots, stem, and leaves have been used for various medicinal purposes (Stander & Van, 1991; McGaw, Jäger, & van Staden, 1997; Sales-Peres et al., 2016; Maroyi, 2017). Regarding the treatment of oral diseases, the roots of this plant are preferably employed—the roots are peeled, chewed, and rubbed on teeth and gums, helping to prevent periodontal disease, caries, and dentinal hypersensitivity (Agbor and Naidoo, 2019, More et al., 2008, Sales-Peres et al., 2016, Stander and Van Wyk, 1991).

Previous studies have isolated some E. natalensis chemical components, to find that naphthoquinones and terpenoids, such as betulin, lupeol, diospirin, neodiospirin, and 7-methyljuglone (Van der Kooy, Meyer & Lall, 2006) are correlated with the antibacterial (Lall & Meyer, 2000), antifungal, (Lall, Weiganand, Hussein, & Meyer, 2006), antimalarial (Ngarivhume, Klooster, de Jong & Van der Westhuizen, 2015), and anticariogenic (Kishore et al., 2014) properties of the plant, among other activities (Chauke et al., 2015, Otieno et al., 2008). Nevertheless, studies evaluating the use of E. natalensis roots specifically for treating periodontal disease and caries pathogens (More et al., 2008, Stander and Van Wyk, 1991) or their cytotoxicity to human cells are scarce (Lall et al., 2005, Lall et al., 2005).

Here, we have (i) evaluated the antibacterial effect of the E. natalensis crude extract and fractions on the main causative agents of periodontal disease and caries; (ii) analyzed their cytotoxic effect on normal human fibroblast cells; and (iii) characterized their chemical composition. We initially hypothesized that the extracts obtained from this plant would effectively kill or inhibit the growth of most of the assayed oral bacteria without being cytotoxic.