Deoxyshikonin reversibly inhibits cytochrome P450 2B6.

Deoxyshikonin, a natural shikonin derivative, is the major component of Lithospermum erythrorhizon and exhibits various pharmacological effects such as lymphangiogenetic, anti-bacterial, wound healing, and anticancer effects. To investigate herb-drug interaction potential associated with deoxyshikonin, we examined the inhibitory effects of deoxyshikonin on eight major cytochrome P450 (CYP) enzymes using cocktail substrate-incubated human liver microsomes. Deoxyshikonin strongly inhibited CYP2B6-catalyzed bupropion hydroxylation, with a K_i value of 3.5 μM, and the inhibition was confirmed using purified human CYP2B6. The inhibition was reversible because the inhibitory effect of deoxyshikonin was not dependent on the preincubation time. Our results indicated that deoxyshikonin-induced drug-drug interaction should be considered when any herb containing deoxyshikonin is used for conventional medications.