Section 3.3. Natural products
Family	Cpd #	Inhibition of P. gingivalis growtha	Inhibition of P. gingivalis virulence factorsb	Anti-biofilm activityb	Cytotoxicityb	Appropriate controlsb
3.3.1. Natural products and their derivatives	92 c	✓	N/A	N/A	N/A	YES (chlorhexidine gluconate)
	93–94 c	✓	N/A	N/A	N/A	NC
	95–97 c	✓	N/A	N/A	N/A	NC
	98 d	✓	N/A	N/A	N/A	YES (chlorhexidine gluconate)
	99–100 c	✓	N/A	N/A	N/A	YES (penicillin G)
	101 c	✓	N/A	Inhibited biofilm growth and disrupted preformed biofilms of S. mutans and A. viscosus	N/A	NO (triclosan)
	102 c	✓	YES: inhibited gingipains Rgp and Kgp from P. gingivalis	Slight inhibition of P. gingivalis biofilm formation	N/A	NC
	103–104 d	✓	N/A	N/A	N/A	YES (penicillin G)
	105–106 c	✓	YES: reduced alveolar bone loss and inflammation induced by LPSs from P. gingivalis	Inhibited biofilm growth and disrupted preformed biofilms of P. gingivalis	NT: human periodontal ligament cells or monocyte-like THP-1 cells	NC
	107–108 c	✓	YES: inhibited adherence of P. gingivalis to GMSM-K cells, inhibited activity against collagenase, and reduced LPS-induced secretion of IL-1β, TNF-α, and IL-8	Disrupted preformed biofilms of P. gingivalis	N/A	NC
			NO: not as active against MMP-9
	109–110 d	✗	YES: inhibited adherence of P. gingivalis to GMSM-K cells, inhibited MMP-9 activity, and reduced secretion of TNF-α and IL-8	No inhibition of P. gingivalis biofilm formation	N/A	NC
			NO: no inhibition of P. gingivalis collagenase activity
	111–116 c	✓	N/A	N/A	N/A	YES (chlorhexidine gluconate)
	117–124 c	✓	N/A	N/A	N/A	YES (chlorhexidine)
	125–131 d	✓	N/A	N/A	N/A	YES (chlorhexidine)
	132–136 c	✓	N/A	N/A	N/A	YES (chlorhexidine dihydrochloride)
	137–153 c	✓	N/A	Inhibited growth of single-species biofilms of S. mutans along with multi-species biofilms (containing S. mutans, A. viscosus, F. nucleatum, and P. gingivalis)	N/A	NO (triclosan)
	154–155 c	✓	YES: inhibited P. gingivalis gingipains	Inhibited biofilm formation of P. gingivalis and A. viscosus	NT: human RBCs and Vero cells	YES (MTZ)
	156–168 c	✗	YES: inhibited AI-2 activity	Inhibited biofilm formation of F. nucleatum	NT: THP-1, human gingival fibroblasts, and HOK-16B	NO ((Z)-4-bromo-5-(bromomethylene)furan-2(5H)-one)
	169 d	✗	N/A	Disrupted P. gingivalis biofilms in combination with other known antibiotics	N/A	YES (cefuroxime, ofloxacin, and MIN)
	170–172 c	✗	YES: reduced mRNA levels of fimA and mfa1	Inhibited the ability of P. gingivalis to attach to S. gordonii	N/A	NC
3.3.2. Essential oils and their derivatives	173–176 c	✓	N/A	Inhibited biofilm formation of P. gingivalis and slightly inhibited preformed biofilm growth	N/A	NO (CBEO and tinidazole)
	177–181 c	✓	N/A	N/A	NT: human fibroblast cells	YES (chlorhexidine dihydrochloride)
	183–185 e	✗	N/A	N/A	T: gingival fibroblasts	YES (chlorhexidine)
					NT: oral keratinocytes
	186–188 e	✗	N/A	Not active against P. gingivalis biofilms	N/A	YES (chlorhexidine)
	189–190 e	✗	N/A	Not active against P. gingivalis biofilms	N/A	YES (AMX)

^a✓ indicates active below 49 μg mL⁻¹ for the best representative compounds in the series as determined by either MIC, CFUs, or % growth inhibition. ✗ indicates not active (>50 μg mL⁻¹) for the best representative compounds in the series as determined by either MIC, CFUs, or % growth inhibition.

^bN/A indicates not available for the best representative compounds in the series. NT indicates not toxic for the best representative compounds in the series. T indicates toxic for the best representative compounds in the series. NC indicates no control used for comparison. YES indicates that an appropriate antibacterial/antiseptic agent FDA-approved for periodontal therapy was used for comparison. NO indicates that either an antibacterial agent approved for indications other than periodontal therapy or not approved by the FDA for any indications was used for comparison.

^cIndicates compounds that displayed good anti-P. gingivalis activity as identified by growth inhibition, virulence factors inhibition, and/or anti-biofilm activity.

^dIndicates compounds that displayed moderate anti-P. gingivalis activity as identified by growth inhibition, virulence factors inhibition, and/or anti-biofilm activity.

^eIndicates compounds that displayed poor anti-P. gingivalis activity as identified by growth inhibition, virulence factors inhibition, and/or anti-biofilm activity.