Author/Authors :
Gao, Chengcheng Nanjing Medical University - Huai’an First People’s Hospital - Department of Gastroenterology, China , Xie, Rui Nanjing Medical University - Huai’an First People’s Hospital - Department of Gastroenterology, China , Ma, Tianheng Nanjing Medical University - Huai’an First People’s Hospital - Department of Gastroenterology, China , Yan, Wei Nanjing Medical University - Huai’an First People’s Hospital - Department of Gastroenterology, China , Pang, Liqun Nanjing Medical University - Huai’an First People’s Hospital - Department of Gastroenterology, China , gao, c. department of gastroenterology,huai an first people s hospital,nanjing medical university,6 beijing road west,huai an, China , xie, r. department of gastroenterology,huai an first people s hospital,nanjing medical university,6 beijing road west,huai an, China , ma, t. department of gastroenterology,huai an first people s hospital,nanjing medical university,6 beijing road west,huai an, China , yan, w. department of gastroenterology,huai an first people s hospital,nanjing medical university,6 beijing road west,huai an, China , pang, l. department of gastroenterology,huai an first people s hospital,nanjing medical university,6 beijing road west,huai an, China
Abstract :
Background: Drug-metabolizing enzymes (DMEs) inhibition based drug-drug interaction and herb-drug interaction severely challenge the R D process of drugs or herbal ingredients. Objective: To evaluate the inhibition potential of wogonin (an important flavonoid isolated from the root of Scutellaria baicalensis) towards one of the most important phase II DMEs, UDP-glucuronosyltransferase (UGT) 1A9. Methods: Both recombinant UGT1A9-catalyzed 4-methylumbelliferone (4-MU) glucuronidation reaction and human liver microsomes (HLMs)-catalyzed propofol glucuronidation reaction were used as two different probe reactions. Results: Wogonin noncompetitively inhibited recombinant UGT1A9-catalyzed 4-MU glucuronidation, and exerted competitive inhibition towards HLMs-catalyzed propofol glucuronidation. The inhibition kinetic parameters (Ki) were calculated to be 3.2 μM and 52.0μM, respectively. Conclusion: Necessary monitoring was needed when wogonin was co-administered with the clinical drugs mainly undergoing UGT1A9-mediated glucuronidation elimination. Additionally, probe reactions-dependent inhibition of wogonin towards the activity of UGT1A9 should be paid attention when translating these in vitro data into in vivo situation.
