# Antimicrobials from Medicinal Plants: An Emergent Strategy to Control Oral Biofilms
## 1 Introduction  
Oral diseases triggered by pathogenic bacteria persevere as a worldwide problem with high impact on human health. More than 750 bacteria species inhabit the oral cavity, some of which are opportunistic species capable of causing infections related to oral biofilm. Epithelial cells, dental surfaces and orthodontic prostheses are examples of oral surfaces favorable to the creation of multispecies biofilms that promote the development of infectious diseases, such as dental caries, gingivitis, and periodontitis, which represent some of the most common chronic oral diseases in adults and children [1, 2, 3, 4]. Dental caries, a medical term for tooth decay or cavities, are part of a group of polymicrobial diseases caused by specific acid-producing bacteria, mainly Gram-positive species, such as _Streptococcus mutans_, _Streptococcus sburnins_ and _Lactobacillus_ spp., responsible for the destruction of the dental enamel and its lower layer, the dentin [5, 6]. These bacteria metabolize sucrose into organic acids, mainly lactic acid, which dissolve calcium phosphate from the teeth causing decalcification and possible decay [7]. On the other hand, periodontal diseases are characterized by the occurrence of severe gum infections that damage the soft tissue and the bone that supports the tooth, most of which caused by the pathogens _Aggregatibacter actinomycetemcomitants_, _Porphyromonas gingivalis_ and _Prevotella intermedia_[5, 8]. Several chemical compounds have been used in the control of oral infectious diseases, like chlorhexidine, fluorine and their combinations [9]. Chlorhexidine is generally acceptedas a chemical antib biofilm agent, widely used in dentistry to preserve the healthy oral microbiome [10]. However, some unwanted side effects have been reported, arising from its use for prolonged periods, which may include tooth pigmentation, burning sensation in the mouth, altered taste, and restocking of the oral cavity by resistant strains [11], the latter being mainly due to an increased resistance to antibiotics and to other synthetic chemicals, with a consequent decrease in their clinical efficacy [2]. Given this, in recent years, one of the adopted strategies to overcome these and other related issues is the use of medicinal plants [12; 13], which have been used as traditional treatments for thousands of years and throughout the world, given their composition in natural bioactive compounds with multiple recognized biological activities [14]. There are several reports of antibacterial and/or antibiofilm activity linked to extracts from a huge variety of plants, mostly related with the presence of secondary metabolites such as flavonoids, phenolic acids, and tannins [15], which play an important role in the resistance to various microbial pathogens and in the protection against free radicals and toxins [16; 17]. Regarding phenolic compounds, several mechanisms through which antimicrobial activity is promoted have been described, since these compounds interact with bacterial proteins and cell membrane structures, damaging and reducing their fluidity, inhibiting the synthesis of nucleic acids, and interfering with the microorganisms' own energy metabolism [16; 18; 19]. On the other hand, the investigation of antibiofilm properties derived from phenolic compounds present in plants has revealed that, in addition to their bactericidal effect, other mechanisms can lead to biofilm suppression, namely through disturbances in its bacterial regulatory mechanisms, such as quorum sensing (QS) [20]. As an example, many catechin-based polyphenols, flavonoids, proanthocyanin oligomers, and some other plant-derived compounds, compromise the formation of biofilm through the inhibition of glucosyltransferases (GTFs) from one of the most important oral pathogens, _S. mutans_[21]. In modern medicine, natural compounds are considered valuable and with undeniable therapeutic assets, showing reduced toxicity and increased efficiency [22].