Over the past few years, the role of intestinal alkaline phosphatase (IAP) as a crucial mucosal defence factor essential for maintaining gut homeostasis has been established. IAP is an important apical brush border enzyme expressed throughout the gastrointestinal tract and secreted both into the intestinal lumen and into the bloodstream. IAP exerts its effects through dephosphorylation of proinflammatory molecules including lipopolysaccharide (LPS), flagellin, and adenosine triphosphate (ATP) released from cells during stressful events. Diminished activity of IAP could increase the risk of disease through changes in the microbiome, intestinal inflammation, and intestinal permeability. Exogenous IAP exerts a protective effect against intestinal and systemic inflammation in a variety of diseases and represents a potential therapeutic agent in diseases driven by gut barrier dysfunction such as IBD. The intestinal protective mechanisms are impaired in IBD patients due to lower synthesis and activity of endogenous IAP, but the pathomechanism of this enzyme deficiency remains unclear. IAP has been safely administered to humans and the human recombinant form of IAP has been developed. This review was designed to provide an update in recent research on the involvement of IAP in intestinal inflammatory processes with focus on IBD in experimental animal models and human patients.

Inflammatory bowel diseases (IBDs) are a group of disorders which include ulcerative colitis and Crohn’s disease. Obesity is becoming increasingly more common among patients with inflammatory bowel disease and plays a role in the development and course of the disease. This is especially true in the case of Crohn’s disease. The recent results indicate a special role of visceral adipose tissue and particularly mesenteric adipose tissue, also known as “creeping fat”, in pathomechanism, leading to intestinal inflammation. The involvement of altered adipocyte function and the deregulated production of adipokines, such as leptin and adiponectin, has been suggested in pathogenesis of IBD. In this review, we discuss the epidemiology and pathophysiology of obesity in IBD, the influence of a Western diet on the course of Crohn’s disease and colitis in IBD patients and animal’s models, and the potential role of adipokines in these disorders. Since altered body composition, decrease of skeletal muscle mass, and development of pathologically changed mesenteric white adipose tissue are well-known features of IBD and especially of Crohn’s disease, we discuss the possible crosstalk between adipokines and myokines released from skeletal muscle during exercise with moderate or forced intensity. The emerging role of microbiota and the antioxidative and anti-inflammatory enzymes such as intestinal alkaline phosphatase is also discussed, in order to open new avenues for the therapy against intestinal perturbations associated with IBD.

Turmeric obtained from the rhizomes of Curcuma longa has been used in the prevention and treatment of many diseases since the ancient times. Curcumin is the principal polyphenol isolated from turmeric, which exhibits anti-inflammatory, antioxidant, antiapoptotic, antitumor, and antimetastatic activities. The existing evidence indicates that curcumin can exert a wide range of beneficial pleiotropic properties in the gastrointestinal tract, such as protection against reflux esophagitis, Barrett’s esophagus, and gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs (NSAIDs) and necrotizing agents. The role of curcumin as an adjuvant in the treatment of a Helicobacter pylori infection in experimental animals and humans has recently been proposed. The evidence that this turmeric derivative inhibits the invasion and proliferation of gastric cancer cells is encouraging and warrants further experimental and clinical studies with newer formulations to support the inclusion of curcumin in cancer therapy regimens. This review was designed to analyze the existing data from in vitro and in vivo animal and human studies in order to highlight the mechanisms of therapeutic efficacy of curcumin in the protection and ulcer healing of the upper gastrointestinal tract, with a major focus on addressing the protection of the esophagus and stomach by this emerging compound.

Inflammatory bowel diseases (IBDs) are a heterogeneous group of disorders exhibited by two major phenotypic forms: Crohn‘s disease and ulcerative colitis. Although the aetiology of IBD is unknown, several factors coming from the adipose tissue and skeletal muscles, such as cytokines, adipokines and myokines, were suggested in the pathogenesis of ulcerative colitis; however, it has not been extensively studied whether voluntary exercise can ameliorate that disorder. We explored the effect of moderate exercise (i.e., voluntary wheel running) on the disease activity index (DAI), colonic blood flow (CBF), plasma irisin and adiponectin levels and real-time PCR expression of proinflammatory markers in mesenteric fat in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis fed a high-fat diet (HFD) compared to those on a standard chow diet (SD). Macroscopic and microscopic colitis in sedentary SD mice was accompanied by a significant fall in CBF, some increase in colonic tissue weight and a significant increase in the plasma levels of tumour necrosis factor-alpha (TNF-α), IL-6, monocyte chemotactic protein 1 (MCP-1) and IL-13 (p < 0.05). In sedentary HFD mice, colonic lesions were aggravated, colonic tissue weight increased and the plasma TNF-α, IL-6, MCP-1, IL-1β and leptin levels significantly increased. Simultaneously, a significant decrease in the plasma irisin and adiponectin levels was observed in comparison with SD mice (p < 0.05). Exercise significantly decreased macroscopic and microscopic colitis, substantially increased CBF and attenuated the plasma TNF-α, IL-6, MCP-1, IL-1β and leptin levels while raising the plasma irisin and the plasma and WAT concentrations of adiponectin in HFD mice (p < 0.05). We conclude that: (1) experimental colitis is exacerbated in HFD mice, possibly due to a fall in colonic microcirculation and an increase in the plasma and mesenteric fat content of proinflammatory biomarkers; and (2) voluntary physical activity can attenuate the severity of colonic damage in mice fed a HFD through the release of protective irisin and restoration of plasma adiponectin.

Metal-based carbon monoxide (CO)-releasing molecules have been shown to exert anti-inflammatory and anti-oxidative properties maintaining gastric mucosal integrity. We are interested in further development of metal-free CO-based therapeutics for oral administration. Thus, we examine the protective effect of representative CO prodrug, BW-CO-111, in rat models of gastric damage induced by necrotic ethanol or aspirin, a representative non-steroidal anti-inflammatory drug. Treatment effectiveness was assessed by measuring the microscopic/macroscopic gastric damage area and gastric blood flow by laser flowmetry. Gastric mucosal mRNA and/or protein expressions of HMOX1, HMOX2, nuclear factor erythroid 2-related factor 2, COX1, COX2, iNos, Anxa1 and serum contents of TGFB1, TGFB2, IL1B, IL2, IL4, IL5, IL6, IL10, IL12, tumor necrosis factor α, interferon γ, and GM-CSF were determined. CO content in gastric mucosa was assessed by gas chromatography. Pretreatment with BW-CO-111 (0.1 mg/kg, i.g.) increased gastric mucosal content of CO and reduced gastric lesions area in both models followed by increased GBF. These protective effects of the CO prodrug were supported by changes in expressions of molecular biomarkers. However, because the pathomechanisms of gastric damage differ between topical administration of ethanol and aspirin, the possible protective and anti-inflammatory mechanisms of BW-CO-111 may be somewhat different in these models.