Antiulcerogenic activity of chlorogenic acid in different models of gastric ulcer

Abstract

Chlorogenic acid (CGA) is found in many foods, including coffee, berries, potatoes, carrots, wine, apples, and various herbs, and has anti-inflammatory, antidiabetic, and antitumoral actions. The CGA is well absorbed orally, and its effects on gastric ulcer have not been previously reported. The present manuscript evaluated the effect of oral administration of CGA on ethanol/HCl (Et/HCl) or nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcer model in male Swiss mice. Animals were pretreated with 0.2 % carboxymethylcellulose (vehicle, p.o.), omeprazole (positive control, 30 mg/kg, p.o.), carbenoxolone (antioxidant positive control, 100 mg/kg, p.o.), or CGA (5, 25, or 50 mg/kg, p.o.). One hour later, the gastric ulcer was induced by injecting Et/HCl solution (100 μL/10 g body weight; Et 60 % + HCl 0.03 M) or piroxicam (100 mg/kg, p.o). After another hour or 4 h later, gastric tissues were collected from Et/HCl or piroxicam-treated animals, respectively, to evaluate the size of the lesion, histological alterations, secretion of gastric acid, neutrophil migration, oxidative/antioxidative enzymes, markers of lipid peroxidation, or concentrations of inflammatory mediators. CGA treatment had a gastroprotective effect in both models, reducing the percentage of lesioned area. CGA treatment did not alter the secretion of gastric action but inhibited neutrophil migration and restored the levels of catalase, superoxide dismutase, glutathione peroxidase, glutathione, and thiobarbituric acid reactive substances in mice treated with Et/HCl. Additionally, CGA treatment blocked the increase of tumor necrosis factor alpha and leukotriene B4 but did not restore the reduced prostaglandin levels in the NSAID-induced ulcer. Together, the data presented herein show that CGA may be a suitable natural compound for the prevention and treatment of gastric lesions caused by a different etiology.

Protective Effects of Chlorogenic Acid against Experimental Reflux Esophagitis in Rats

“…Unexpectedly, CGA did not affect pH level, while omeprazole, an irreversible inhibitor of H + , K + -ATPase, showed strong effects on gastric content pH, confirming its anti-secretory effects. Our results agree with those of a previous report indicating that CGA does not interfere with gastric secretion or the pH of gastric juices in mice with pyloric ligatures (Shimoyama et al, 2013). Moreover, this characteristic of CGA might supplement the side effects of long term treatment of PPI such as hypochlorhydria or rebound hypersecretion that could lead to PPI-deficiency (Reimer et al, 2009).…”

“…CGA, a phenolic compound with antiinflammatory and antioxidant properties, inhibited lipopolysaccharide-induced inflammatory cytokines release in RAW264.7 cells (Shan et al, 2009). Most recently, CGA inhibited neutrophil migration and restored the levels of antioxidant enzymes in ethanol/HCl-and piroxicam-induced gastric ulcer models, suggesting protective effects against gastrointestinal tract inflammation (Shimoyama et al, 2013). However, the effects and precise mechanisms of CGA in RE have not been studied until now.…”

“…Moreover, we previously reported the protective effects of CGA against experimental inflammatory disorders: CGA inhibited high mobility group box 1 release and toll-like receptor 4 signaling pathways in liver during both septic and ischemic insult, suggesting its potential in immunomodulation Yun et al, 2012). Most recently, CGA was shown to suppress HCl/ethanol-and piroxicam-induced gastric mucosal injury (Shimoyama et al, 2013) while its high absorption capacity to gastric and intestinal cells by oral route is focused (Farah et al, 2008;Stalmach et al, 2010). However, the effects of CGA on RE have not been studied.…”

“…No effects of these vehicles on esophagus function were detected. The dose range of the drugs and the time of administration were chosen based on previous reports (Miwa et al, 2009;Shimoyama et al, 2013) and our preliminary studies.…”

Effectiveness of Sidr Honey on the prevention of ethanol-induced gatroulcerogenesis: role of antioxidant and antiapoptotic mechanism

“…Many animal models of gastroulcerogenesis are used such as ethanol-or pylorus ligation-induced gastric ulcer. 13,14 Therefore, the current study was designed to investigate the effectiveness of sidr monofloral honey (SH) against ethanol-induced gastric ulcerogenesis.…”