TABLE 3.

The effect of propolis on CYP450 in vitro, in vivo, and human.

Propolis samples	Subjects	Alteration on CYP450 enzymes	Key results	References
Propolis containing products (source and composition not specified)	Infected HepG2 cells with five P450-expressing adenoviruses (Ad-CYP1A2, Ad-CYP2C9, Ad-CYP2C19, Ad-CYP2D6, and Ad-CYP3A4)	↓ CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4	The propolis containing product simultaneously inhibited CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4 activities by more than 50%	Sasaki et al. (2017)
Ethanol extract of Brazilian green propolis (EEP-B55)	Human recombinant CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 microsomes expressed in baculovirus-insect cells	↓CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4	EEP-B55 inhibited the activities of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 in vitro with IC50 values of 4.07, 2.62, 9.53, 18.9, and 20.6 μg/ml, respectively	Naramoto et al. (2014)
Propolis extract with characterized chemical composition	Human liver microsomes	↓CYP1A2, CYP2E1, and CYP2C19	Propolis extract inhibited CYP1A2, CYP2E1, and CYP2C19 with IC50 values of 6.9, 16.8, and 43.1 μg/ml. It showed no change on CYP2A6, CYP2B6, CYP2C9, CYP2D6, and CYP3A4	Ryu et al. (2016)
		No effect on CYP2A6, CYP2B6, CYP2C9, CYP2D6, and CYP3A4	In addition, the addition of propolis decreased the metabolites of duloxetine which is metabolized by CYP1A2 and CYP2D6, suggesting a possible drug–herb interaction of propolis and duloxetine
Standardized propolis extract (EPP-AF®)	Healthy adult volunteers	No clinical change on CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A	EPP-AF® did not show any clinical change on CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A activities, and the changes for AUC values of caffeine, losartan, omeprazole, metoprolol, midazolam, and fexofenadine were all below 20% when co-administered	Cusinato et al. (2019)