Effects of Lycium Babarum Polysaccharides and C-Phycocyanin on Healing of Ethanol- or Drug-Induced Gastric Ulcer

Peptic ulcer disease, a common disease of the digestive system, involves the erosion of mucosa, submucosa, and muscular layers on the lower esophagus, stomach, or duodenum partially due to the action of acidic gastric juice. The prevalence of peptic ulcer and gastric ulcer was 9.4% and 4.7% in Taiwan, respectively. Chronic alcohol abuse and long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) are the major risk factors for the development and complications of gastric ulcer. The evidence has shown that abnormal oxygen free radical generation may be involved in the pathogenesis of peptic ulcer. Lycium chinense is in the family Lycium, Solanaceae, and Solanales, and its fruit goji or wolfberry, particularly Lycium barbarum L., has been widely used for traditional Chinese medicine. The active components of Lycium barbarum L. including polysaccharides, zeaxanthine, betaine, cerebrosides, taurine, scopoletin, pyrrole derivatives, and trace amounts of zinc, iron, and copper. Lycium barbarum polysaccharides (LBPs) have been reported to have antioxidant, immunomodulation, regeneration, anti-diabetes, anti-osteoporosis, antitumor, anti-fatigue, radioprotection, hepatoprotection, and neuroprotection actions. C-phycocyanin (PC) is a major biliprotein pigment of Spirulina platensis (cyanobacterium; blue-green algae), has been approved as a dietary supplement in many countries including Japan, and commonly used in food coloring and cosmetics. C-phycocyanin has a variety of physiological and regulatory functions including antioxidant, anti-inflammatory, anticancer, hepatoprotective, and wound healing properties. Therefore, it is reasonably hypothesized that LBPs and/or PC may be helpful for the healing of damaged gastric mucosa through lowering oxidative damage, inhibiting proinflammatory response, enhancing cytoprotective defense, regulating autophagy, suppressing apoptosis, and modulating microbiota. The objectives of this study are to (1) investigate the in vitro treatment effects of LBPs and/or PC on the healing of rat or human damaged gastric epithelial cell lines (the 1st year), (2) study the in vivo effects of LBPs and/or PC on the healing in rats with ethanol-, aspirin-, or indomethacin-induced gastric ulcer, and determine whether LBPs and/or PC have the protective effects on gastric ulcer via antioxidant, anti-inflammatory, cytoprotective, autophagy-regulatory, anti-apoptotic, and microbiota-modulatory actions (the 2nd year), and (3) explore the in vitro effects and mechanisms of LBPs and/or PC on the regulation of signaling pathways of inflammation, cytoprotection, autophagy, and apoptosis in ethanol- or NSAIDs-induced gastric lesion (the 3rd year). RGM-1 and GES-1 cells, rat or human normal gastric mucosal epithelial cell lines, respectively, will be exposed to various concentrations of LBPs and/or PC prior to the induction of cell damage by exposure to ethanol, aspirin, or indomethacin. Cell proliferation, integrity of cell membrane, antioxidant activity, proinflammatory cytokines, and cytoprotective factors will be measured. In the in vivo study, rats will be pretreated with LBPs and/or PC for 1 week, induced gastric ulcer by ethanol, aspirin, or indomethacin for 3 weeks, and continuously treated with LBPs and/or PC for another 1 week after the induction. Pathological assessment, cell proliferation, intragastric acidity, oxidative damage, inflammatory response, cytoprotective defense, autophagy, apoptosis, and microbiota will be evaluated. Finally, RGM-1 and GES-1 cells will be exposed to various concentrations of LBPs and/or PC prior to the induction of cell damage by exposure to ethanol, aspirin, or indomethacin, and expression of mediators in the signaling pathways of inflammation, cytoprotection, autophagy, and apoptosis will be analyzed. From the results of the in vitro and in vivo studies, it is to clarify if LBPs and/or PC can inhibit gastric acid secretion, lower oxidative damage, decrease proinflammatory cytokines, improve cytoprotective defense, regulate autophagy, suppress apoptosis, and modulate microbiota to accelerate the healing of damaged gastric mucosa. Furthermore, it can be considered to apply LBPs and/or PC to human clinical trials in the future.