A mannitol-modified emodin nano-drug restores the intestinal barrier function and alleviates inflammation in a mouse model of DSS-induced ulcerative colitis

作者：Yin-Yue Xu, Min Zhu, Jiang Wu, Longbiao Luo, Sijing Dong, M Zhang, Xue Liu, Ke Wang, Hua Luo, Wanghui Jing, Lin Wang, Sicen Wang · 发表于：Chinese Medicine · 年份：2023 · DOI：10.1186/s13020-023-00801-0 · 被引用次数：30 · 研究领域：Inflammatory Bowel Disease、Barrier Structure and Function Studies、Gut microbiota and health

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 present in various medicinal herbs, has demonstrated therapeutic effects against UC. However, low bioavailability due to poor water solubility limits its clinical applications. METHODS: Emodin-borate nanoparticles (EmB) were synthesized to improve drug solubility, and they modified with oligomeric mannitol into microgels (EmB-MO) for targeted delivery to intestinal macrophages that express mannose receptors. UC was induced in a mouse model using dextran sulfate sodium (DSS), and 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 using enzyme-linked immunosorbent assay. 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 UC, 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 than those of EmB and s...