Current drug therapies for ulcerative colitis (UC) are not completely effective in managing moderate-to-severe UC and approximately 20% of patients with severe UC require surgical interventions. Heparins, polydisperse mixtures of non-anticoagulant and anticoagulant oligosaccharides, are widely used as anticoagulants. However, heparins are also reported to have anti-inflammatory properties. Unfractionated heparin was initially used in patients with UC for the treatment of rectal microthrombi. Surprisingly, it was found to be effective in reducing UC-associated symptoms. Since then, several pre-clinical and clinical studies have reported promising outcomes of heparins in UC. In contrast, some controlled clinical trials demonstrated no or only limited benefits, thus the potential of heparins for the treatment of UC remains uncertain. This review discusses potential mechanisms of action of heparins, as well as proposed reasons for their contradictory clinical effectiveness in the treatment of UC.
Inflammatory bowel diseases, such as ulcerative colitis, cause significant morbidity and decreased quality of life. The currently available treatments are not effective in all patients, can be expensive and have potential to cause severe side effects. This prompts the need for new treatment modalities. Enoxaparin, a widely used antithrombotic agent, is reported to possess anti-inflammatory properties and therefore we evaluated its therapeutic potential in a mouse model of colitis. Acute colitis was induced in male C57BL/6 mice by administration of dextran sulfate sodium (DSS). Mice were treated once daily with enoxaparin via oral or intraperitoneal administration and monitored for colitis activities. On termination (day 8), colons were collected for macroscopic evaluation and cytokine measurement, and processed for histology and immunohistochemistry. Oral but not intraperitoneal administration of enoxaparin significantly ameliorated DSS-induced colitis. Oral enoxaparin-treated mice retained their body weight and displayed less diarrhea and fecal blood loss compared to the untreated colitis group. Colon weight in enoxaparin-treated mice was significantly lower, indicating reduced inflammation and edema. Histological examination of untreated colitis mice showed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and the presence of edema, while all aspects of this pathology were alleviated by oral enoxaparin. Reduced number of macrophages in the colon of oral enoxaparin-treated mice was accompanied by decreased levels of pro-inflammatory cytokines. Oral enoxaparin significantly reduces the inflammatory pathology associated with DSS-induced colitis in mice and could therefore represent a novel therapeutic option for the management of ulcerative colitis.