Acetylshikonin is a Novel Non ‐selective Cytochrome P450 Inhibitor

Abstract Acetylshikonin is biologically active compound with anti‐cancer and anti‐inflammatory activity, which is isolated from the root of Lithospermum erythrorhizoma. We have recently discovered a inhibitory effect of acetylshikonin against CYP2J2 activity. Based on this result, we expanded our study to evaluate the inhibitory effects of acetylshikonin against nine different cytochrome P450 (P450) isoforms in human liver microsomes (HLMs) using substrate cocktails incubation assay. Acetylshikonin showed strong inhibitory effect against all P450s tested with IC50 values of 1.4–4.0 μM. Pre‐incubation of acetylshikonin with HLMs and NADPH did not alter inhibition potency, indicating that acetylshikonin is not a mechanism‐based inhibitor. SKF‐525A, a widely used non‐specific P450 inhibitor, had no inhibitory activity against CYP1A2, 2A6, 2E1, and 2J2 while it showed inhibitory effect against CYP2B6, CYP2C19, and 2D6 with IC50 values of 2.5, 3.6, and 0.5 μM, respectively. Our findings indicate that acetylshikonin may be a novel general P450 inhibitor, which could replace SKF‐525A.
Source: Biopharmaceutics and Drug Disposition - Category: Drugs & Pharmacology Authors: Tags: SHORT COMMUNICATION Source Type: research