Pharmacokinetic and Pharmacodynamic Studies of Four Major Phytochemical Components of Da-Cheng-Qi Decoction to Treat Acute Pancreatitis

Abstract

The medicinal herb formulation Da-Cheng-Qi decoction (DCQD) has been shown to ameliorate the severity of acute pancreatitis by regulating an apoptosis–necrosis switch in cells. The active components responsible for this effect and their detailed mechanism of action remain unclear. Here we determine the pharmacokinetic characteristics of the four most abundant compounds in DCQD using a rat model of severe acute pancreatitis. Acute pancreatitis-like symptoms were first induced in rats and then they were given DCQD orally. Rhein was found in rat serum at much higher levels than magnolol, hesperidin, or naringin, even though it was the least abundant of the four compounds in the DCQD. We also examined pharmacodynamics in AR42J cells stimulated with 10−8 M cerulein as a cellular model of acute pancreatitis. After pretreating AR42J cells with individual compounds and then exposing them to cerulein, we determined cell viability, levels of apoptosis and necrosis, and numbers of cells positive for reactive oxygen species (ROS). Pretreatment with any of the four DCQD compounds increased cell viability and the apoptosis index, while also reducing necrosis and ROS generation. The compounds showed maximal effect in AR42J cells around the same time that they showed maximum serum concentration in rats. Although all four components appear to play a role in an apoptosis–necrosis cellular switch in vitro, rhein may be the most bioactive DCQD ingredient. Keywords:: Da-Cheng-Qi decoction, pharmacokinetic/pharmacodynamics, acute pancreatitis, cytoprotection