It has been shown Sunitinib clinical that reactive oxygen and nitrogen species (ROS and RNS) contribute to the acinar cell damage during the early phases of pancreatitis . ROS can act as a molecular trigger to activate oxidant-sensitive nuclear transcription factor kappa B (NF-��B) and thus induces cytokine expression, participating in various inflammatory processes. Moreover, an important link between ROS generation and apoptosis has been shown in both human and experimental pancreatitis. Numerous studies have shown many anti-oxidant treatments significantly reduce pancreatic injury and inflammation . In AP, cytokines and other mediators derived from the inflamed pancreas activate the production of the inducible nitric oxide synthase (iNOS).
An enhanced formation of nitric oxide (NO) due to the induction of iNOS may be an important factor in the systemic and local haemodynamic disturbances and regulation of pancreatic exocrine secretion associated with AP. Excess of NO cause hypotension and decrease blood perfusion of various organs, including the pancreas and lung, correlating with apoptotic changes . Therefore, treatments that could regulate free radicals ROS or RNS may directly contribute to the modality of acinar cell death and the degree of inflammation. Dachengqi Decoction (DCQD) composed of Radix et Rhizoma Rhei (Dahuang), Cortex Magnoliae Officinalis (Houpu), Fructus Aurantii Immaturus (Zhishi) and Natrii Sulphas (Mangxiao) is traditionally used as the representative prescription purgative for the treatment of constipation and for clearing internal heat in the stomach and intestine .
In China, DCQD has been used to treat AP for over 30 years . Recent studies have shown that DCQD can promote gastrointestinal motility, inhibit cytokine activity and immune inflammatory response in AP �C. However, most of its biological activities have been studied individually on its ingredients. Studies designed to test the molecular mechanisms of the compound herb formula DCQD in the modality of pancreatic acinar cell death have not been elucidated to date. Thus, in our present work, we studied the effect of DCQD in regulating the inflammatory response via selective induction of pancreatic acinar cell apoptosis and explored the regulation mechanism of apoptosis/necrosis switch through its opposite effect in regulating ROS and NO in vitro and in vivo.
Materials and Methods 1. Materials 1.1. Drugs and reagents The spray-dried Radix et Rhizoma Rhei, Cortex Magnoliae Officinalis, Fructus Aurantii Immaturus and Natrii Sulphas powder were purchased from Chengdu Green Herbal Pharmaceutical Co. Ltd (Chengdu, China). The spray-dried powder was mixed of an equal amount and reconstituted Dacomitinib with sterile distilled water at concentrations for the crude drug of 2 g/mL DCQD in vivo study .