Palmitic acid (PA) can lead to intestinal epithelial barrier dysfunction. In this study, the protective effects and working mechanisms of 6-shogaol against PA-induced intestinal barrier dysfunction were investigated in human intestinal epithelial Caco-2 cells. Transepithelial electrical resistance (TEER), paracellular flux, qRT-PCR, immunofluorescence, and Western blot experiments showed that the 24-h treatment with 400 μM PA damaged intestinal barrier integrity, as evidenced by a reduction of 48% in the TEER value, a 4.1-fold increase in the flux of fluorescein isothiocyanate-dextran 4000 (FD-4), and decreases in the mRNA and protein expression of tight junction (TJ)-associated proteins (claudin-1, occludin, and ZO-1), compared with the control. The PA treatment significantly (p < 0.05) increased the levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha (TNF-α)) in Caco-2 cells due to the upregulation of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), phosphorylated nuclear factor kappa-B (NF-κB) proteins, and downregulation of miR-216a-5p (which directly targeted TLR4). Co-treatment with PA and 6-shogaol (2.5 μM) significantly (p < 0.05) attenuated PA-induced changes through regulation of TJs via the miR-216a-5p/TLR4/NF-κB signaling pathway. This study provides insights into the functions and working mechanisms of 6-shogaol as a promising food-derived agent against PA-induced intestinal epithelial barrier dysfunction.

Quercetin is a flavonol found in edible plants and possesses a significant anticancer activity. This study explored the mechanism by which quercetin prevented liver cancer via inducing apoptosis in HepG2 cells. Quercetin induced cell proliferation and apoptosis through inhibiting YY1 and facilitating p53 expression and subsequently increasing the Bax/Bcl-2 ratio. The results revealed that YY1 knockdown promoted apoptosis, whilst YY1 overexpression suppressed apoptosis via direct physical interaction between YY1 and p53 to regulate the p53 signaling pathway. Molecular docking using native and mutant YY1 proteins showed that quercetin could interact directly with YY1, and the binding of quercetin to YY1 significantly decreased the docking energy of YY1 with p53 protein. The interactions between quercetin and YY1 protein included direct binding and non-bonded indirect interactions, as confirmed by cellular thermal shift assay, UV-Vis absorption spectroscopy, fluorescence spectroscopy and circular dichroism spectroscopy. It was likely that quercetin directly bound to YY1 protein to compete with p53 for the binding sites of YY1 to disrupt the YY1-p53 interaction, thereby promoting p53 activation. This study provides insights into the mechanism underlying quercetin’s anticancer action and supports the development of quercetin as an anticancer therapeutic agent.

In this study, a surfactant-mediated ultrasonic-assisted process was used for the first time to produce an antioxidant-enriched extract from Chaenomeles speciosa (Sweet) Nakai (C. speciosa, a popular fruit grown widely in the temperate regions of China). Ultrasonic treatment at 51 °C and 200 W for 30 min with sodium dodecyl sulfate as the surfactant led to a phenolic yield of 32.42 mg/g from dried C. speciosa powder, based on single-factor experiments, the Plackett–Burman design and the Box–Behnken design. The phenolic content increased from 6.5% (the crude extract) to 57% (the purified extract) after the purification, using LSA-900C macroporous resin. Both the crude and purified extracts exhibited a significant total reducing power and DPPH/ABTS scavenging abilities, with the purified extract being more potent. The purified extract exerted significant antioxidant actions in the tert-butyl hydroperoxide-stimulated HepG2 cells, e.g., increasing the activities of superoxide dismutase and catalase, while decreasing the reactive oxygen species and malondialdehyde levels, through the regulation of the genes and proteins of the Nrf2/Keap1 signaling pathway. Therefore, the extract from C. speciosa is a desirable antioxidant agent for the oxidative damage of the body to meet the rising demand for natural therapeutics.