Non-Anticoagulant Oligosaccharides of Enoxaparin Relieve Chemical-Induced Acute Colitis

Enoxaparin, a low molecular weight heparin, is commonly used for the treatment and prophylaxis of thromboembolic disorders. Apart from its anticoagulant properties, enoxaparin is known to possess anti-inflammatory activities and therefore could potentially be useful for the management of chronic inflammatory conditions. However, the clinical use of enoxaparin in inflammation is deterred by the risk of bleeding, attributed to the presence of anticoagulant oligosaccharides. It is proposed that non-anticoagulant oligosaccharides of enoxaparin are predominantly responsible for its anti-inflammatory activity. We isolated oligosaccharides of enoxaparin using ion-exchange chromatography and the anti-inflammatory potential of oligosaccharides was evaluated in a mouse model of acute colitis. Male C57BL/6 mice were administered dextran sulphate sodium through drinking water and were subsequently treated orally with oligosaccharides of enoxaparin. Compared to untreated animals, oral enoxaparin oligosaccharide-treated mice showed reduced severity of colitis. Importantly, since the oligosaccharides of enoxaparin with no or minimal anticoagulant activity were found to be responsible for this protective effect, these molecules could be developed as novel therapeutic agents for the management of ulcerative colitis.