Jun Guo1, Chenming Ni2, Xiaoyang Liu3, Tao Liu4. 1. Department of Neurology, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, P.R. China. 2. Laboratory of Pharmacology, Department of Pharmacy, Jinan Military General Hospital, Jinan 250031, P.R. China. 3. Department of Hepatobiliary Surgery, Jinan Military General Hospital, Jinan 250031, P.R. China. 4. Department of Dermatology, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, P.R. China.
Abstract
BACKGROUND: Ganoderic acid B is an important bioactive ingredient isolated from Ganoderma lucidum, and exhibits various pharmacological activities. AIMS: To investigate the influence of Ganoderic acid B towards the therapeutic window of trifluoperazine (TFP). METHODS: In vitro human liver microsomes (HLMs) incubation system was used to determine the inhibition of Ganoderic acid B towards the glucuronidation of trifluoperazine (TFP). RESULTS: Ganoderic acid B exerted concentration-dependent inhibition towards the glucuronidation of TFP. Furthermore, Dixon plot was used to determine the inhibition type. The intersection point was located in the second quadrant in Dixon plot, indicating the competitive inhibition of Ganoderic acid B towards TFP glucuronidation. Through fitting the data using competitive nonlinear fitting equation, the inhibition kinetic parameter was calculated to be 56.7 uM. CONCLUSION: All this data indicated the potential influence of Ganoderic acid B-containing herbs towards therapeutic window of TFP. Given that the glucuronidation reaction of TFP is the probe reaction of UGT1A4, the data obtained from the present study also indicated the potential influence of Ganoderic acid-containing herbs towards the therapeutic window of drugs mainly undergoing UGT1A4-mediated metabolism.
BACKGROUND:Ganoderic acid B is an important bioactive ingredient isolated from Ganoderma lucidum, and exhibits various pharmacological activities. AIMS: To investigate the influence of Ganoderic acid B towards the therapeutic window of trifluoperazine (TFP). METHODS: In vitro human liver microsomes (HLMs) incubation system was used to determine the inhibition of Ganoderic acid B towards the glucuronidation of trifluoperazine (TFP). RESULTS:Ganoderic acid B exerted concentration-dependent inhibition towards the glucuronidation of TFP. Furthermore, Dixon plot was used to determine the inhibition type. The intersection point was located in the second quadrant in Dixon plot, indicating the competitive inhibition of Ganoderic acid B towards TFP glucuronidation. Through fitting the data using competitive nonlinear fitting equation, the inhibition kinetic parameter was calculated to be 56.7 uM. CONCLUSION: All this data indicated the potential influence of Ganoderic acid B-containing herbs towards therapeutic window of TFP. Given that the glucuronidation reaction of TFP is the probe reaction of UGT1A4, the data obtained from the present study also indicated the potential influence of Ganoderic acid-containing herbs towards the therapeutic window of drugs mainly undergoing UGT1A4-mediated metabolism.
Authors: Zhican Wang; Timothy Wong; Takanori Hashizume; Leslie Z Dickmann; Michele Scian; Nicholas J Koszewski; Jesse P Goff; Ronald L Horst; Amarjit S Chaudhry; Erin G Schuetz; Kenneth E Thummel Journal: Endocrinology Date: 2014-03-18 Impact factor: 4.736