Glycated α-lactalbumin based micelles for quercetin delivery: Physicochemical stability and fate of simulated digestion.

Glycated protein is a kind of promising material that can improve the bioavailability of bioactive compounds and achieve sustained release under digestion. In this study, the α-lactalbumin (ALA)-dextran conjugates synthesized by Maillard reaction were fabricated to load and protect quercetin. Quercetin-loaded micelles stabilized by the ALA-dextran conjugates 1:4 showed the smallest size (428.57 ± 5.64 nm) with highest encapsulation efficiency (94.38% ± 0.50%) of quercetin. Compared to ALA/dextran mixture complex, the conjugates-based micelles had better pH, ionic strength and photothermal stability. Furthermore, the micelles composed of the conjugates 1:2 and 1:4 showed the best controlled release effect during the simulated digestion, releasing 62.41% and 66.15% of quercetin from the total encapsulated contents, respectively, which was mainly related to the resistance of glycated ALA to the enzymes. The findings indicated that ALA-dextran conjugates could be effectively designed for the ideal delivery system of hydrophobic bioactive compounds in food industry.

Chlorogenic acid improves the intestinal barrier by relieving endoplasmic reticulum stress and inhibiting ROCK/MLCK signaling pathways.

Phenolic acids play an active role in protecting the intestinal barrier, the structural integrity and function of which are crucial for host health. In the present study, we aimed to identify phenolic compounds that protect the intestine and explore the underlying mechanisms. We performed an imaging-based, quantitative, high-content screening (using Caco-2 and LS174T incubated with lipopolysaccharide/palmitic acid, respectively) to identify phenolic acids that could improve the mucosal barrier. We found that chlorogenic acid (CGA), 5-caffeoylquinic acid, protocatechuic acid, and caffeic acid alleviated intestinal barrier disruption. Furthermore, CGA increased transepithelial electrical resistance (TEER) and decreased paracellular permeability. Mechanistically, CGA inhibited the activation of myosin light chain kinase (MLCK) and Rho-associated kinase 1 (ROCK1) signals, thereby downregulating the expression of the downstream molecules phosphorylated myosin phosphatase target subunit 1 (p-MYPT1), MLCK, and phosphorylated myosin light chain (p-MLC), and upregulating the expression of tight junction proteins. In addition, CGA alleviated endoplasmic reticulum (ER) stress by inhibiting the expression levels of ER markers [glucose-regulated protein78 (GRP78) and C/EBP homologous protein (CHOP)] and the nuclear translocation of activating transcription factor 6 (ATF6), thereby promoting the expression of mucin [mucin 2 (Muc2), mucin 5AC (MUC5AC)] and secretory factor trefoil factor family 3 (TFF3) proteins. In summary, we identified four substances that can stabilise intestinal homeostasis. Of these, CGA protects the intestinal barrier by inhibiting ROCK/MLCK signalling pathways and relieving ER stress. These findings highlight the importance of rapidly screening potential active ingredients that benefit the intestinal barrier and provide a theoretical basis for enteral nutrition.

Regulatory effects of flavonoids luteolin on BDE-209-induced intestinal epithelial barrier damage in Caco-2 cell monolayer model.

Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants (POPs). They are constantly detected in foods. PBDEs can disrupt the intestinal flora, but enterotoxicity is unknown. Luteolin, one kind of flavonoid, has drawn increasing interest as an agent that strengthens the intestinal barrier. This study aimed to evaluate the mitigating effect of luteolin on damage to the intestinal barrier induced by decabromodiphenyl ether (BDE-209) in a Caco-2 cell monolayer model. Results showed that luteolin mitigated BDE-209-induced damage to intestinal epithelial barrier by reducing the levels of reactive oxygen species (ROS), increasing the activity of superoxide dismutase (SOD) and glutathione (GSH), suppressed the secretion of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß), and increased the expression of tight junction (TJ) proteins (ZO-1, occludin, and claudin-1). Furthermore, the protective effects were related to the inhibition of extracellular regulated protein kinases (ERK) and nuclear factor kappa-B (NF-κB)/myosin light chain kinase (MLCK) signaling pathways, and the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. This study is the first to provide strong evidence that BDE-209 can damage the intestinal barrier, and we here investigated the important protective effect of luteolin, which may lay the foundation for the development of luteolin as a dietary supplement to strengthen the intestinal barrier.