# Propolis as Natural Product in the Oral Cavity Bacterial Infections Treatment: A Systematic Review
## 3 Antibacterial Properties of Propolis: Mode of Action  
Propolis interacts with lipids in the plasma membrane, increases membrane permeability, disrupts membrane potential and adenosine triphosphate (ATP) production, inhibits bacterial motility [49; 53], cell envelope [54], efflux pumps [54], generates ion imbalance in the microenvironment of the bacteria [53], as well as inhibits bacterial proteins and nucleic acids synthesis [55]. Phenolic compounds and flavonoids play a crucial role in the antibacterial activity of propolisis [47]. Flavonoids (pinocembrin and apigenin) have antibacterial activity against \(S\). _mutans_ and \(S\). _sobrinus_[49]. Flavonoids (galangin, pinocembrin, and pinostrobin) increase bacterial membrane permeability, inhibit bacterial genetic coding, nucleic acid synthesis, the attachment and formation of biofilms, and energy metabolism of bacteria [52]. The B ring of flavonoids inhibits bacterial nucleic acid synthesis [55]. Up to now, three pathways leading to disruption of the bacterial membrane by propolis are known: (I) attaching to the bacteria cell wall, which leads to cell lysis and bacteria's death; (II) the interaction between the hydrophobic parts of the membrane and the polar headgroup of propolisis; (III) ability to inhibit protein synthesis. Moreover, flavonoids are able to bind to bacterial cell walls leading to the lysis of the cells or inhibiting bacterial growth by the inhibition of topoisomerase IV-dependent deactivation activity [55]. Apigenin is a potent inhibitor of glucosyltransferases B and C [56], peptidoglycan synthesis, and \(\beta\)-lactamase enzymes, and it alters the outer and cytoplasmic membrane permeabilization [57]. Lipophilic properties of Tt-farnesol alter the permeability and fluidity of the cell membrane and affect its glycolytic activity, production-secretion of glucosyltransferases and acidurance [56]. Caffeic acid phenethyl ester also increases bacterial membrane permeability and inhibits bacterial RNA polymerase [58]. In case of _P. gingivalis_, atrepillin C (a phenolic compound) causes membrane blebbing and is responsible for bacteriostatic activity [49]. 3-Prenyl-cinnamic acid allyl ester and 2-dimethyl-8-prenylchromene, which are found in propolisis, also possess antimicrobial activity [49]. Propolis also inhibits the activity of glycosyltransferase enzyme via the synthesis induction of insoluble glycan. Thus, propolisis possesses antimicrobial activity against \(S\). _circuits_, \(S\). _mutans_, and \(S\). _sobrinus_[46]. The inhibition of the cell envelope synthesis is possible by the inhibition of (I) \(\beta\) hydroxyacyl-ACP dehydrase, (II) \(\beta\)-hydroxyacyl-acyl carrier protein dehydratase, (III) fatty acid synthase-type II (FAS-II) and (IV) Ala-Ala synthetase. Flavonoids are also able to inhibit the synthesis of cell envelopes. Quercetin, apigenin, and sakuranetin inhibit \(\beta\) hydroxyacyl-ACP dehydrase and act as competitive inhibitors of \(\beta\)-hydroxyacyl-acyl carrier protein dehydratase. \(\beta\)-hydroxyacyl-ACP is a key component for bacterial membrane and substrates for the acyltransferases (catalyze early steps in lipopolysaccharide saccharide biosynthesis), which are important for bacterial survival. Quercetin, kaempfer, fiestin, myricetin, and morin may inhibit FAS-II, which is important for membrane biogenesis. Apigenin, galangin, and kaempferf inhibit Ala-Ala synthetase [54]. Baicalein, morin, silibinin, sylimarin, 6-prenylapigenin, and isobavachalcon inhibit electron transport chain and ATP synthesis [54]. Galangin increases in potassium loss, leading to direct cytoplasmic membrane damage of the bacterial cell wall [57]. Cinnamic acid possesses antimicrobial activity, since it can inhibit the production and function of ATPases, cell division, and biofilm formation. This is possible due to damaging the bacterial cell membrane and disrupting the key metabolic pathways with a stress on the inhibition of intracellular pH homeostasis [49; 55].