S/O/W Emulsion with CAPE Ameliorates DSS-Induced Colitis by Regulating NF-κB Pathway, Gut Microbiota and Fecal Metabolome in C57BL/6 Mice.

Inflammatory bowel disease (IBD) has attracted much attention worldwide due to its prevalence. In this study, the effect of a solid-in-oil-in-water (S/O/W) emulsion with Caffeic acid phenethyl ester (CAPE, a polyphenolic active ingredient in propolis) on dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice was evaluated. The results showed that CAPE-emulsion could significantly alleviate DSS-induced colitis through its effects on colon length, reduction in the disease activity index (DAI), and colon histopathology. The results of ELISA and Western blot analysis showed that CAPE-emulsion can down-regulate the excessive inflammatory cytokines in colon tissue and inhibit the expression of p65 in the NF-κB pathway. Furthermore, CAPE-emulsion promoted short-chain fatty acids production in DSS-induced colitis mice. High-throughput sequencing results revealed that CAPE-emulsion regulates the imbalance of gut microbiota by enhancing diversity, restoring the abundance of beneficial bacteria (such as Odoribacter), and suppressing the abundance of harmful bacteria (such as Afipia, Sphingomonas). The results of fecal metabolome showed that CAPE-emulsion restored the DSS-induced metabolic disorder by affecting metabolic pathways related to inflammation and cholesterol metabolism. These research results provide a scientific basis for the use of CPAE-emulsions for the development of functional foods for treating IBD.

Caffeic acid phenethyl ester loaded in a targeted delivery system based on a solid-in-oil-in-water multilayer emulsion: Characterization, stability, and fate of the emulsion during in vivo digestion.

Many studies have shown that caffeic acid phenethyl ester (CAPE) has various functions, such as antioxidant, anti-inflammatory and anticancer activity, but its low bioavailability and stability limit its application. In this study, the colorectal targeted delivery system for CAPE based on a solid-in-oil-in-water (S/O/W) multilayer emulsion was prepared using CAPE-loaded nanoparticles as the solid phase, coconut oil as the oil phase, and a mixture of lecithin and sodium caseinate as the aqueous phase. The stability of the O/W interfacial layer was improved by using a sodium casein-lecithin mixture as the aqueous surface layer in the preparation. This S/O/W emulsion is a spherical droplet with an S/O/W trilayer structure with a particle size of 155.5 ± 0.72 nm and a polydispersity index (PDI) of 0.24 ± 0.01. The Fourier transform infrared (FTIR) results confirmed that CAPE was successfully loaded into the S/O/W emulsion. This S/O/W emulsion was able to maintain a stable liquid state at pH 6.00-7.4 or cholate concentration of 0-50 mg/mL but showed a gel state at pH 2.0-3.0. The storage experiments demonstrated that the S/O/W emulsion was stable for 15 days at 4 °C, but was prone to agglomeration and emulsion breakage at 25 °C. The in vivo digestion process indicated that the S/O/W emulsion was gradually digested in the digestive tract and released solid phase nanoparticles in the large intestine. Therefore, this newly developed targeted delivery system can effectively deliver CAPE to the colorectum and achieve a 12-hour delayed release, which improved the bioavailability and activity of CAPE.