Background: Gomisin G, isolated from herb Schisandra chinensis, exhibits anti-tumor activities. Therefore, Gomisin G is a drug candidate for anti-liver cancer therapy. Aims: To predict the metabolic behavior and metabolism-based drug-drug interaction of gomisin G. Methods: Molecular docking method was used. The crystal structure of CYP3A4 with the ligand ketoconazole was chosen from protein data bank (http://www.rcsb.org/pdb). Chemdraw software was used to draw the two-dimensional structure of gomisin G with standard bond lengths and angles. Results: Gomisin G can be well docked into the activity site of CYP3A4, and distance between gomisin G the heme active site was 2.75 Å. To evaluate whether the inhibitors of CYP3A4 can affect the metabolism of gomisin G, co-docking of gomisin G and ketoconazole was further performed. The distance between ketoconazole and activity center (2.10 Å) is closer than the distance between gomisin G and activity center of CYP3A4, indicating the easy influence of CYP3A4's strong inhibitor towards the metabolism of gomisin G. Conclusion: Gomisin G is a good substrate of CYP3A4, and CYP3A4 inhibitors easily affect the metabolism of Gomisin G.
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.
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