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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.

The impairment of intestinal motility and related infectious complications are the predominant clinical phenomenon in patients with severe acute pancreatitis (SAP). We aimed to investigate the effects of Da-Cheng-Qi decoction (DCQD) on the gastrointestinal injury in SAP patients and the potential mechanism involved in rats. DCQD was enema administered to 70 patients for 7 days in West China Hospital. Mortality and organ failure during admission were observed and blood samples for laboratory analysis were collected. We also experimentally examined plasma inflammatory cytokines in rat serum and carried the morphometric studies of the gut. Intestinal propulsion index and serum and tissue vasoactive intestinal peptide (VIP) were also detected. Though DCQD did not affect the overall incidence of organ failure, it shortened the average time of paralytic intestinal obstruction and decreased the morbidity of infectious complications in patients with SAP. Compared with untreated rats, the DCQD lowered the levels of proinflammatory cytokine and decreased the mean pathological intestinal lesion scores. The VIP level in intestinal tissue or serum in DCQD group was obviously lowered and intestinal propulsion index was significantly improved. In conclusion, DCQD has good effect on pancreatitis-associated intestinal dysmotility in patients and in rat models. [ABSTRACT FROM AUTHOR]