TY - JOUR
T1 - Evaluation of the inhibition risk of shikonin on human and rat UDP-glucuronosyltransferases (UGT) through the cocktail approach
AU - Cheng, Yi
AU - Tang, Shuowen
AU - Chen, Ang
AU - Zhang, Yuanjin
AU - Liu, Mingyao
AU - Wang, Xin
N1 - Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/9/15
Y1 - 2019/9/15
N2 - Shikonin, a natural red colorant, is widely used for food garnishment and cosmetic ingredient in the world. Shikonin also possesses a variety of pharmacological actions, including anti-inflammation and anti-cancer activities. However, little is known about its effects on the UDP-glucuronosyltransferases (UGT) activity. Therefore, the aim of this study was to evaluate the effect of shikonin on the UGT1A1, UGT1A3, UGT1A6, UGT1A9 and UGT2B7 activities via the human and rat liver microsomal assay and cocktail approach. The results showed shikonin inhibited human and rat liver microsomal UGT activity only in a dose-dependent manner. The further enzyme kinetic studies demonstrated that shikonin was not only a competitive inhibitor of human UGT1A1, UGT1A9, and UGT2B7, but also presented competitive inhibition on rat UGT1A1 and AZTG reactions. In conclusion, shikonin as a reversible inhibitor of UGT enzyme has a high-risk potential to cause the possible toxicity, especially drug-drug or food-drug interactions.
AB - Shikonin, a natural red colorant, is widely used for food garnishment and cosmetic ingredient in the world. Shikonin also possesses a variety of pharmacological actions, including anti-inflammation and anti-cancer activities. However, little is known about its effects on the UDP-glucuronosyltransferases (UGT) activity. Therefore, the aim of this study was to evaluate the effect of shikonin on the UGT1A1, UGT1A3, UGT1A6, UGT1A9 and UGT2B7 activities via the human and rat liver microsomal assay and cocktail approach. The results showed shikonin inhibited human and rat liver microsomal UGT activity only in a dose-dependent manner. The further enzyme kinetic studies demonstrated that shikonin was not only a competitive inhibitor of human UGT1A1, UGT1A9, and UGT2B7, but also presented competitive inhibition on rat UGT1A1 and AZTG reactions. In conclusion, shikonin as a reversible inhibitor of UGT enzyme has a high-risk potential to cause the possible toxicity, especially drug-drug or food-drug interactions.
KW - Chenodeoxycholic acid (PubChem CID: 10133)
KW - Cocktail method
KW - Estradiol (PubChem CID: 5757)
KW - Human liver microsomes
KW - Propofol (PubChem CID: 4943)
KW - Reversible inhibitor
KW - Serotonin (PubChem CID: 5202)
KW - Shikonin
KW - UDP-glucuronosyltransferases (UGT)
KW - Zidovudine (PubChem CID: 35370)
UR - https://www.scopus.com/pages/publications/85066265980
U2 - 10.1016/j.toxlet.2019.05.017
DO - 10.1016/j.toxlet.2019.05.017
M3 - 文章
C2 - 31128210
AN - SCOPUS:85066265980
SN - 0378-4274
VL - 312
SP - 214
EP - 221
JO - Toxicology Letters
JF - Toxicology Letters
ER -
