Safety Evaluation for Utilization of 6-shogaol in the Ascites of Patients with Liver Cancer

Limited therapeutic methods exist for the ascites of patients with liver cancer, and development of new drugs from herbs is very important and necessary. 6-shogaol, the major component isolated from ginger, is drawing more and more attention due to its multiple biochemical and pharmacological activities, such as anti-inflammation, analgesic, antipyretic, antioxidant, and anticancer properties. 6-shogaol exerts therapeutic-potential towards the-ascites of patients with liver cancer. The present study aims to determine the influence of 6-shogaol towards the metabolism of two important clinical drugs irinotecan and propofol. 6-shogaol did not affect the activity of human carboxylesterase 2-catalyzed hydrolysis of irinotecan and UDP-glucuronosyltransferase (UGT) 1A1-catalyzed glucuronidation of SN-38 which is the active metabolite of irinotecan. 6-shogaol exerted strong inhibition towards the glucuronidation of propofol. Noncompetitive inhibition of 6-shogaol towards propofol glucuronidation was demonstrated with the inhibition kinetic parameter (Ki) to be 3.5 mu M. In silico docking of 6-shogaol towards the activity cavity of UGT1A9 was employed to explain the inhibition of 6-shogaol towards propofol glucuronidation. All these results were helpful for the development of 6-shogaol as the drug to treat ascites of patients with liver cancer.