Natural products in caries research: current (limited) knowledge, challenges and future perspective.

Dental caries is the most prevalent and costly oral infectious disease worldwide. Virulent biofilms firmly attached to tooth surfaces are prime biological factors associated with this disease. The formation of an exopolysaccharide-rich biofilm matrix, acidification of the milieu and persistent low pH at the tooth-biofilm interface are major controlling virulence factors that modulate dental caries pathogenesis. Each one offers a selective therapeutic target for prevention. Although fluoride, delivered in various modalities, remains the mainstay for the prevention of caries, additional approaches are required to enhance its effectiveness. Available antiplaque approaches are based on the use of broad-spectrum microbicidal agents, e.g. chlorhexidine. Natural products offer a rich source of structurally diverse substances with a wide range of biological activities, which could be useful for the development of alternative or adjunctive anticaries therapies. However, it is a challenging approach owing to complex chemistry and isolation procedures to derive active compounds from natural products. Furthermore, most of the studies have been focused on the general inhibitory effects on glucan synthesis as well as on bacterial metabolism and growth, often employing methods that do not address the pathophysiological aspects of the disease (e.g. bacteria in biofilms) and the length of exposure/retention in the mouth. Thus, the true value of natural products in caries prevention and/or their exact mechanisms of action remain largely unknown. Nevertheless, natural substances potentially active against virulent properties of cariogenic organisms have been identified. This review focuses on gaps in the current knowledge and presents a model for investigating the use of natural products in anticaries chemotherapy.