In vitro assessment of CYP1A2 and 2C9 inhibition potential of Withania somnifera and Centella asiatica in human liver microsomes.
BACKGROUND
Several herbal drugs and allopathic medicines when co-administered can lead to severe herb-drug interactions. Hence, this study was undertaken in order to assess the in vitro inhibition potential of Withania somnifera and Centella asiatica with cytochrome P450 (CYP) 1A2 and 2C9 enzyme using human liver microsomes.


METHODS
Inhibitory potential of crude extracts of both the medicinal plants along with their principal phytoconstituents were investigated using selective probe substrate technique. IC50, Ki values and mode of inhibition were determined.


RESULTS
The results of the study revealed that W. somnifera showed no significant interaction with both the isoforms of CYP. However, ethanolic extract of C. asiatica significantly inhibited both CYP1A2 (IC50 value - 42.23±3.65 μg/mL/Ki value - 14.93±4.59 μg/mL) and 2C9 enzyme (IC50 value - 48.41±4.64 μg/mL/Ki value - 23.89±3.14 μg/mL) in a competitive manner. The flavonoids, quercetin and kaempferol showed potent (IC50 values less than 10 μM) inhibition of CYP1A2 activity with no significant inhibition of CYP2C9 enzyme.


CONCLUSIONS
Thus, these findings of the study might be helpful for safe and effective use of C. asiatica in clinical practice. However, its in vivo interaction study in humans is still warranted.
Jay
J
Savai
Alice
A
Varghese
Nancy
N
Pandita
Meena
M
Chintamaneni
D028041:Centella; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D065729:Cytochrome P-450 CYP2C9 / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology*; D041743:Herb-Drug Interactions / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000201:enzymology*; D010936:Plant Extracts / Q000494:pharmacology; D010946:Plants, Medicinal; D032341:Withania
D065607:Cytochrome P-450 Enzyme Inhibitors; D010936:Plant Extracts; D065729:Cytochrome P-450 CYP2C9; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2