Uncovering New Anticariogenic Agents
by Zachary R. Conley
The formation of dental plaque involves a rather ordered pattern of bacterial colonization. As the teeth erupt (or if they are cleaned), surfaces of the enamel are first coated with conditioning film which is characterized by molecules from the host (e.g., saliva) and from the bacteria (e.g., secreted by-products). Early colonizers will grow and change the local conditions to increase its suitability for more discriminating species which colonize later, attaching to previously bound bacteria by adhesion-receptor mechanisms. Biofilm efficiently produce acid via their metabolism of carbohydrates, leading to demineralization of hard dental tissue. In order to prevent caries, it is essential to set our targets on the formation process of dental biofilms. 1
Anticariogenic compounds that are able to target the mechanisms of biofilm formation are gaining interest in recent history, and provide effective supplements to typical mechanical oral cleaning methods.
Milk proteins have been shown experimentally to interfere with the process of bacterial colonization on surfaces coated in saliva. A more recent study showed the effect of bovine milk osteopontin (OPN), a phosphorylated whey glycoprotein, on in vitro models of dental biofilm. It was found that OPN was able to bind to the cell surfaces of bacteria and reduce biofilm formation, even when introduced 12 hours post-initiation of the biofilm. Moreover, it had a significant impact on reducing the amount of biofilm that formed and its stability. This compound may be a valuable accessory to future oral hygiene protocols if these results can be translated to in vivo models.2
Epigallocatechin Gallate (EGCG):
Tea is said to be the most widely consumed beverage in today’s world and is known to contain numerous bioactive components. Epigallocatechin gallate is an antimicrobial component of tea catechins and, in a recent study, showed an interference of attachment of S. mutans. EGCG inhibited in vitro growth of S. mutans in medium and had a minimum bactericidal concentration of 62.5 µg/ml. EGCG is able to reduce S. mutans’ biofilm formation by suppression of gtf expression associated with biofilm formation and cell adherence and is thus takes its action at sub-lethal doses. This is an exciting natural anticariogenic compound that can prevent biofilm without having to suppress the growth of the oral bacteria population.3,4
Ginkgo biloba, a component of the extract from Ginkgo leaves and seeds, has been widely used in traditional Chinese medicine. Furthermore, Ginkgolic acids are a group of compounds in Ginkgo biloba and have attracted attention as a result of their bioactive properties (e.g., antitumor and antimicrobial effects). One recent paper investigated the effects of ginkgogenolic acid against S. mutans to see whether it would interfere with bacterial adherence, biofilm formation, and other factors. Ginkgoneolic acid was found to inhibit the adherence of S. mutans at a concentration of 2 μg/mL. When ginkgoneolic acid’s antimicrobial capabilities were evaluated in vitro, it was shown to be bactericidal against S. mutans at even 4 μg/mL. Moreover, this agent was able to successfully inhibit formation of a biofilm. This natural product might be a promising future therapeutic agent if experiments with multi-species biofilms can produce the similar results.5,6
It is necessary to conduct basic science, translational, and clinical research on potential new anticariogenic agents in order to stay on the cutting edge of caries prevention. Many natural products contain antimicrobial properties and may provide useful in prevention of biofilm formation. As our discovery and characterization of new cavity-preventative compounds progresses, we will be able significantly advance the effectiveness of preventative therapies that are currently available to patients.
1. P.D. Marsh, Are dental diseases examples of ecological catastrophes?
Microbiology, 149 (2) (2003), pp. 279–294
2. Schlafer S, Raarup MK, Wejse PL, Nyvad B, Städler BM, et al. (2012) Osteopontin Reduces Biofilm Formation in a Multi-Species Model of Dental Biofilm. PLoS ONE 7(8): e41534. doi:10.1371/journal.pone.0041534
3. Xin Xu, Xue D. Zhou, Christine D. Wu, Tea catechin epigallocatechin gallate inhibits Streptococcus mutans biofilm formation by suppressing gtf genes. Archives of Oral Biology, Volume 57, Issue 6, June 2012, Pages 678–683
4. C.D. Wu, G.X. Wei, Tea as a functional food for oral health. Nutrition, 18 (5) (2002), pp. 443–444
5. Zhou C,Li X,Du W,Feng Y,Kong X,Li Y,Xiao L,Zhang P(2010)Antitumor effects of ginkgolic acid in human cancer cell occur via cell cycle arrest and decrease the Bcl-2/Bax ratio to induce apo- ptosis. Chemotherapy 56:393–402
6. He J, Wang S, Wu T, Cao Y, Xu X, Zhou X, Effects of ginkgoneolic acid on the growth, acidogenicity, adherence, and biofilm of Streptococcus mutans in vitro. Folia Microbiol (Praha). 2012 Sep 6; . Epub 2012 Sep 6.