PMID- 36355111 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230308 IS - 2218-1989 (Print) IS - 2218-1989 (Electronic) IS - 2218-1989 (Linking) VI - 12 IP - 11 DP - 2022 Oct 26 TI - Attenuation of Palmitic Acid-Induced Intestinal Epithelial Barrier Dysfunction by 6-Shogaol in Caco-2 Cells: The Role of MiR-216a-5p/TLR4/NF-kappaB Axis. LID - 10.3390/metabo12111028 [doi] LID - 1028 AB - 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 muM 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-1beta, and tumor necrosis factor-alpha (TNF-alpha)) 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-kappaB) proteins, and downregulation of miR-216a-5p (which directly targeted TLR4). Co-treatment with PA and 6-shogaol (2.5 muM) significantly (p < 0.05) attenuated PA-induced changes through regulation of TJs via the miR-216a-5p/TLR4/NF-kappaB 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. FAU - Ouyang, Fangxin AU - Ouyang F AD - College of Food Science and Engineering, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. FAU - Li, Bo AU - Li B AD - Department of Nursing, Jinan Vocational College of Nursing, 3636 Gangxi Road, Jinan 250102, China. FAU - Wang, Yuli AU - Wang Y AD - College of Food Science and Engineering, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. FAU - Xu, Longhua AU - Xu L AD - College of Food Science and Engineering, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. FAU - Li, Dapeng AU - Li D AD - College of Food Science and Engineering, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. FAU - Li, Feng AU - Li F AUID- ORCID: 0000-0003-0611-2735 AD - College of Food Science and Engineering, Shandong Agricultural University, 61 Daizong Street, Taian 271018, China. FAU - Sun-Waterhouse, Dongxiao AU - Sun-Waterhouse D AD - School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand. LA - eng GR - 2021TZXD007/Project of Key R&D Program of Shandong Province/ GR - N/A/Incubation Program of Youth Innovation in Shandong Province/ GR - ZR2022MC004/Natural Science Foundation of Shandong Province/ PT - Journal Article DEP - 20221026 PL - Switzerland TA - Metabolites JT - Metabolites JID - 101578790 PMC - PMC9692742 OTO - NOTNLM OT - 6-shogaol OT - intestinal epithelial barrier OT - miR-216a-5p/TLR4 OT - palmitic acid OT - tight junctions COIS- The authors declare no conflict of interest. EDAT- 2022/11/11 06:00 MHDA- 2022/11/11 06:01 PMCR- 2022/10/26 CRDT- 2022/11/10 11:14 PHST- 2022/09/22 00:00 [received] PHST- 2022/10/19 00:00 [revised] PHST- 2022/10/21 00:00 [accepted] PHST- 2022/11/10 11:14 [entrez] PHST- 2022/11/11 06:00 [pubmed] PHST- 2022/11/11 06:01 [medline] PHST- 2022/10/26 00:00 [pmc-release] AID - metabo12111028 [pii] AID - metabolites-12-01028 [pii] AID - 10.3390/metabo12111028 [doi] PST - epublish SO - Metabolites. 2022 Oct 26;12(11):1028. doi: 10.3390/metabo12111028.