Objective: Acanthopanax senticosus Harms extract (ASE) is an ingredient of functional foods, such as health supplements, in Japan. We investigated the effects of ASE on CYP2C9 activity.
Methods and Results: CYP2C9-catalyzed diclofenac 4′-hydroxylase activities in human intestinal and liver microsomes (abbreviated as HIM and HLM, respectively) were significantly decreased by the addition of ASE in a concentration-dependent manner. Kinetic studies of diclofenac 4′-hydroxylase in HLM revealed that ASE addition significantly decreased V_max but had no effect on K_m. These results suggest that diclofenac 4′-hydroxylase activity is suppressed by ASE addition in a non-competitive manner. Then, we investigated the time courses of diclofenac 4′-hydroxylase activity in rat liver microsomes after ASE oral administration (50 to 400 mg/kg). Diclofenac 4′-hydroxylase activities were significantly lowered by the administration of 200 and 400 mg/kg ASE at 0.5 to 4 hr compared with control (0 hr). Furthermore, we investigated the effects of ASE oral administration on the pharmacokinetics of tolbutamide (substrate for CYP2C9) in rats. The area under the concentration-time curve of tolbutamide after ASE oral administration (400 mg/kg) was enhanced by approximately 1.6 times compared with that without ASE oral administration.
Conclusion: These findings indicated that ASE inhibits human intestinal and hepatic CYP2C9 activities.

Objective: By using human liver microsomes (HLM), we analyzed the effects of 14 known components of A.senticosus Harms on the activities of CYP2C9 and CYP3A4.
Methods and Results: Sesamin and quercetin inhibited both enzyme activities, whereas quercitrin strongly inhibited CYP3A4 activity. The 50% inhibitory concentrations (IC₅₀s) of sesamin and quercetin on CYP2C9 activity were approximately 124- and 59-fold higher and the IC₅₀s of sesamin, quercetin, and quercitrin on CYP3A4 activity were approximately 427-, 135-, and 22-fold higher than that of A. senticosus Harms extract (ASE), respectively. All these components inhibited both CYP3A4 and CYP2C9 in a non-competitive manner. However, these components are present in small amounts in ASE.
Conclusion: Therefore, the food-drug interactions caused by A. senticosus Harms are presumed to be due to the additive or synergistic interaction of these components or the other existing components, including their metabolites.

Three patients, who received infrarenal aorto-iliac bifurcation grafts, complained of flaccid and insensible feeling on lower extremities immediatedly after surgery. These symptoms were supposed due, in two cases, to spinal cord ischemia or, in remaining one case, to ischemic change of the peripheral nerve, In former cases, spinal cord hypoxia might be caused by interrupted blood supply through spinal artery as it was intercepted temporarily but for about three and a half hours during surgical procedures. In the latter case, cramping of the left iliac artery lasted for five and a half hours, which might result in anoxic damage of the peripheral nerve. Hyperbaric oxygenation (HBO) at two atmospheric absolute (ATA) pressure for 75min and 3 ATA for 90min were repeated everyday for them. In all cases, almost complete sensorimotor recovery was obtained after 15 to 30 instances of HBO, which was combined with physical therapy. HBO seemed to have improved early hypoxic and edematous damages of the spinal cord or peripheral nerve. As an unfavorable complication of abdominal aortic surgery, incidence of sensorimotor disturbance of the extremities is infrequent and/or unpredictable, however, once it occurs, no effective therapeutic maneuvers were developed yet. Through these clinical data, HBO should be introduced more actively for such disorders. One of the key issues to enhance the effect of HBO is that, HBO should be introduced as soon as possible once postoperative nuerologic disorders were diagnosed.