*2.3.8 Natural agents*

Alkaloids are a group of natural organic compounds that contain a nitrogen atom and are present in different species of plants. The alkaloid berberine has been reported to inhibit biofilm formation in *S. epidermidis* biofilm at a concentration of 30 μg/mL, possibly via binding to the amyloid proteins in the biofilm matrix [127]. Reserpine has been shown to effectively prevent biofilm formation in *K. pneumoniae* at a concentration of 0.0156 mg/mL, which was 64-fold lower than its minimum inhibitory concentration [128]. Tetrandrine inhibited biofilm formation of *C. albicans* at a concentration of 32 mg/L, which is the MIC50 of that alkaloid against *C. albicans* SC5314 [129].

Guaijaverin, a flavonoid obtained from the leaves of *Psidium guajava*, has been shown to prevent the attachment of *S. mutans* to smooth surfaces by 83.7% at a concentration of 500 μg/mL. Eembelin, which is isolated from *Embelia ribes*, has been shown to inhibit biofilm formation in *S. mutans* [130]. Macelignan, isolated from the nutmegs of *Myristica fragrans*, was shown to reduce more than 50% of *S. mutans* biofilm at a concentration of 10 μg/mL [131].

Terpenes are a large class of natural hydrocarbons that are synthesized in microorganisms, plants and animals. Bakuchiol, isolated from the seeds of *Psoralea corylifolia*, has been shown to inhibit the adherence of *S. mutans* [132]. Other examples for terpenes that inhibit biofilm formation in *S. mutans*, are Xanthorrhizol (in combination with chlorhexidine gluconate) and casbane diterpene [133, 134].
