The mannitol-modified emodin nano drug restored the intestinal barrier function and alleviated inflammation in a mouse model of DSS-induced colitis

Abstract

Abstract Background Ulcerative colitis (UC) is an inflammatory disease of the colon that is characterized by mucosal ulcers. Given its increasing prevalence worldwide, it is imperative to develop safe and effective drugs for treating UC. Emodin, a natural anthraquinone derivative presenting in various medicinal herbs, has demonstrated therapeutic effects against colitis. However, low bioavailability due to poor water solubility limits its clinical applications. Methods Emodin-borate nanoparticles (EmB) were synthesized to improve drug solubility, and modified with oligomeric mannitol into microgels (EmB-MO) for targeted delivery to intestinal cells expressing mannose receptors. Colitis was induced in a mouse model using dextran sulphate sodium (DSS), and the different drug formulations were administered to the mice via drinking water. The levels of inflammation-related factors in the colon tissues and fecal matter were measured by enzyme linked immunosorbent assay (ELISA). Intestinal permeability was evaluated using fluorescein isothiocyanate dextran. HE staining, in vivo imaging, real-time PCR and western blotting were performed to assess intestinal barrier dysfunction. Results Both EmB and EmB-MO markedly alleviated the symptoms of colitis, including body weight loss, stool inconsistency and bloody stools, and restored the levels of pro- and anti-inflammatory cytokines. However, the therapeutic effects of EmB-MO on the macroscopic and immunological indices were stronger compared to that of EmB, and similar to that of 5-aminosalicylicacid. Furthermore, EmB-MO selectively accumulated in the inflamed colon epithelium, and restored the levels of the gut barrier proteins ZO-1 and occludin. Conclusions Encapsulation of EmB-MO significantly improved water solubility, which translated to greater therapeutic effects on the immune balance and gut barrier function in mice with DSS-induced colitis. Our findings provide novel insights into developing emodin-derived drugs for the management of UC.