Accumulating evidence has shown that high-fat diet (HFD) can lead to intestinal epithelial barrier dysfunction. We previously found that 6-shogaol was able to attenuate palmitic acid (PA)-induced intestinal barrier damages in human intestinal epithelial Caco-2 cells through regulation of tight junctions (TJs). However, the in vivo protective effects and action mechanism of 6-shogaol against HFD-induced intestinal barrier dysfunction remains unexplored. In this study, HFD-fed C57BL/6J mice were used as the intestinal barrier dysfunction model to investigate the protective effects of 6-shogaol. The results showed that the 6-shogaol significantly (P < 0.05) suppressed HFD-stimulated increase of serum fluorescein isothiocyanate (FITC)-dextran level and proinflammatory cytokines (interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha (TNF-α)) in the ileum, whilst significantly (P < 0.05) increased the expression of TJ-associated proteins (e.g., Zona occludens 1, occludin, and claudin-1). Furthermore, miR-sequencing and qRT-PCR analysis revealed that miR-215-3p_R+1 was one of the highest expressed miRNAs in the ileum in response to the 6-shogaol treatment. MiR-215-3p_R+1 overexpression significantly (P < 0.01) downregulated occludin expression in PA-treated Caco-2 cells compared with the mimics NC+PA+6-shogaol group, partially compromising the protective effects 6-shogoal against intestinal epithelial barrier dysfunction. Taken together, these findings provide the evidence for the first time that 6-shogaol has the potential to treat HFD-induced TJs impairment via the miR-215-3p_R+1/occludin axis.

MicroRNAs (miRNAs) are a class of single-stranded and non-coding endogenous RNAs with 18-25 nucleotides in length. By binding to the complementary sequences in the 3′-untranslated region (3′-UTR) of protein coding genes, miRNAs regulate posttranscriptionally the mRNA expression of target genes and enzymes involved in various biological processes. The application of high-throughput sequencing, bioinformatics analysis, and novel detection methods has high-lighted promising roles of miRNAs as both novel biomarkers for tumor diagnosis and critical regulators involved in almost all stages of carcinogenesis including cancer initiation, promotion and progression. Epigallocatechin-3-gallate (EGCG), the most investigated active catechin in green tea, has been linked to various health-promoting benefits including chemoprevention and treatment of cancers. In this review, we first present a brief description of EGCG and its major metabolic pathway. It is followed by reviewing the roles of EGCG in the modulation of oncogenic and tumor suppressing miRNAs in some common cancers. These findings suggest that the capacity of EGCG to regulate expression of specific miRNAs provides insights of its new mechanisms of action underlying its chemopreventive and potential beneficial activities against various cancers.

The intestinal barrier plays a key role in preventing harmful substance invasions and maintaining intestinal homeostasis, with tight junction proteins being essential for maintaining the integrity of the intestinal barrier. This review summarizes the structural composition of the intestinal barrier, the role of tight junction in maintaining intestinal physiological functions, with an emphasis on the potential application value of the major phenolic components in ginger, 6-gingerol and 6-shogaol, for alleviating tight junction damage. Through comprehensive analysis of clinical research and experimental results in recent years, it is found that 6-gingerol and 6-shogaol can improve the expression levels of tight junction-related proteins and maintain the integrity and biofunction of the intestinal barrier by inhibiting inflammation, oxidative stress and apoptosis as well as regulating the composition of intestinal microbiota. This paper provides a theoretical basis and insights for understanding the mechanisms of action of ginger phenolic compounds in regulating health and for expanding their application scopes.

Food allergy has become a global concern. Spleen tyrosine kinase (SYK) inhibitors are promising therapeutics against allergic disorders. In this study, a total of 300 natural phenolic compounds were firstly subjected to virtual screening. Sesamin and its metabolites, sesamin monocatechol (SC-1) and sesamin dicatechol (SC-2), were identified as potential SYK inhibitors, showing high binding affinity and inhibition efficiency towards SYK. Compared with R406 (a traditional SYK inhibitor), sesamin, SC-1, and SC-2 had lower binding energy and inhibition constant (K_i) during molecular docking, exhibited higher bioavailability, safety, metabolism/clearance rate, and distribution uniformity ADMET predictions, and showed high stability in occupying the ATP-binding pocket of SYK during molecular dynamics simulations. In anti-dinitrophenyl-immunoglobulin E (Anti-DNP-IgE)/dinitrophenyl-human serum albumin (DNP-HSA)-stimulated rat basophilic leukemia (RBL-2H3) cells, sesamin in the concentration range of 5–80 μmol/L influenced significantly the degranulation and cytokine release, with 54.00% inhibition against β-hexosaminidase release and 58.45% decrease in histamine. In BALB/c mice, sesamin could ameliorate Anti-DNP-IgE/DNP-HSA-induced passive cutaneous anaphylaxis (PCA) and ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) reactions, reduce the levels of allergic mediators (immunoglobulins and pro-inflammatory cytokines), partially correct the imbalance of T helper (Th) cells differentiation in the spleen, and inhibit the phosphorylation of SYK and its downstream signaling proteins, including p38 mitogen-activated protein kinases (p38 MAPK), extracellular signal-regulated kinases (ERK), and p65 nuclear factor-κB (p65 NF-κB) in the spleen. Thus, sesamin may be a safe and versatile SYK inhibitor that can alleviate IgE-mediated food allergies.