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 similar to those of 5-aminosalicylic acid. Furthermore, EmB-MO selectively accumulated in the inflamed colon epithelium and restored the levels of the gut barrier proteins such as ZO-1 and Occludin. Conclusions: EmB-MO encapsulation significantly improved water solubility, which translated to greater therapeutic effects on the immune balance and gut barrier function in mice with DSS-induced UC. Our findings provide novel insights into developing emodin-derived drugs for the management of UC.
This study demonstrated both adipose‐derived stem cells (ASCs) in vitro and in vivo combined with three‐dimensional (3D) porous sponge matrices on implant wound healing. Sponge matrices were created from hyaluronic acid (HA), collagen (Col), and gelatin (Gel), constructing two types: HA‐L (low content) and HA‐H (high content), to be cross‐linked with 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide (EDC). Fourier transform infrared spectroscopy method verified carboxyl groups of HA and amino groups of Col and Gel reacting between the raw materials and scaffolds to identify the successive cross‐linking. The swelling ratios of two types of sponge matrices were analyzed by water absorption capabilities, and the results displayed both over 30‐fold dry scaffold weight enhancements. In biodegradation tests, matrices were hydrolyzed over time by three cutaneous enzymes, hyaluronidase, lysozyme, and collagenase I. ASCs from rats were cultured within the HA‐H scaffold, demonstrating higher antioxidative abilities and secretions on related genes and proteins compared to the other two groups. The ASC HA‐H matrix promoted cell proliferation to stimulate capillary angiogenesis inducer secretions, including vascular endothelial growth factor (VEGF) and transforming growth factor‐β (TGF‐β). In vivo histological examinations showed ASCs from implanted HA‐H implant transported into the subcutis, and rat skin cells also infiltrated into the original matrix zone to increase the extracellular matrix (ECM) reconstructions. Our experimental data revealed that the ASC HA‐H sponge implant was effective in improving wound repair.
10 August 2023 in International Journal of Biological Macromolecules