TABLE 2

Recommended enzymes, transporters, and experimental systems for screening natural products for inhibition and/or induction

Adapted with permission from the American Society for Pharmacology and Experimental Therapeutics from Johnson et al. (2018).

Cytochrome P450 enzymes
 Essential: CYP1A2, CYP2B6, CYP2C19, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A
Experimental SystemInhibitionInduction
Recombinant enzymesAs neededNA
Human liver microsomesaNA
Human hepatocytesAs neededa
Human intestinal microsomesAs neededNA
Human intestinal cellsAs neededAs neededb
Human kidney microsomesAs neededNA
Human kidney cellsAs neededAs neededb
Other cell linesAs neededNA
UGTs
Essential: UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A8, UGT1A9, UGT1A10, UGT2B7, UGT2B10, UGT2B15
Experimental SystemInhibitionInduction
Recombinant enzymesAs neededNA
Human liver microsomesaNA
Human hepatocytesaa
Human intestinal microsomesAs neededNA
Human intestinal cellsAs neededAs neededb
Human kidney microsomesAs neededNA
Human kidney cellsAs neededAs neededb
Other cell linesAs neededNA
Other Enzymes that May Be Considered
hCE1, hCE2, SULT1A1, SULT1A3, SULT1B1, SULT1E1, SULT2A1
Experimental SystemInhibitionInduction
Recombinant enzymesaNA
Human liver microsomesaNA
Human hepatocytesAs neededa
Human intestinal microsomesAs neededNA
Human intestinal cellsAs neededbAs neededb
Human kidney microsomesAs neededbNA
Human kidney cellsAs neededbAs neededb
Transporters
Essential: BCRP, BSEP, MATE1, MATE2-K, MRP2, MRP3, NTCP, OATP1B1, OATP1B3, OATP2B1, OAT, OCT, P-gp
Experimental SystemInhibitionInduction
Transfected cell lines (single, double)aNA
Human intestinal cellsAs neededbAs neededb
Human kidney cellsAs neededbAs neededb
Human hepatocytesaa
Membrane vesiclesaNA
  • BCRP, breast cancer resistance protein; BSEP, bile salt export pump; hCE, human carboxylesterase; MATE, multidrug and toxin extrusion protein; MRP, multidrug resistance–associated protein; NA, not applicable; NTCP, sodium taurocholate–cotransporting polypeptide; OAT, organic anion transporter; OATP, organic anion–transporting polypeptide; OCT, organic cation transporter; P-gp, P-glycoprotein; SULT, sulfotransferase.

  • a Essential system. Inhibition studies in hepatocytes may involve multiple transporters.

  • b These models represent an emerging field and will be refined with time. Expression levels of enzymes and transporters in these models are lower than those in vivo (Speer et al., 2019; Chapron et al., 2020; Kasendra et al., 2020).