Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China.
J Agric Food Chem. 2022 Sep 14;70(36):11301-11313. doi: 10.1021/acs.jafc.2c04101. Epub 2022 Sep 6.
The effectiveness of resveratrol (RES) on intestinal barrier dysfunction and colitis has been extensively studied. However, the specific effects of its microbial metabolites on gut barrier function remain unclear. Hence, we compared the protective effects of RES and its microbial metabolites dihydroresveratrol (DHR) and 3-(4-hydroxyphenyl)-propionic acid (4HPP) against intestinal barrier injury and colitis. Only 4HPP and RES significantly reduced paracellular permeability and the secretion of proinflammatory cytokines in lipopolysaccharides (LPS)-treated intestinal Caco-2 cells, which was consistent with the upregulation in tight junction (TJ) proteins. Furthermore, RES and 4HPP ameliorated intestinal barrier dysfunction and colonic inflammation in colitis mice, while DHR did not. In particular, the expressions of intestinal TJ proteins and Muc2 were restored by RES and 4HPP. The molecular mechanism involved the adenosine monophosphate-activated protein kinase (AMPK)-mediated activation of CDX2 and the regulation of the SIRT1/NF-κB pathway. These findings provide new insights into understanding the protective effects of RES against intestinal barrier damage and colitis.
白藜芦醇（RES）对肠道屏障功能障碍和结肠炎的有效性已经得到了广泛的研究。然而，其微生物代谢物对肠道屏障功能的确切影响尚不清楚。因此，我们比较了 RES 及其微生物代谢物二氢白藜芦醇（DHR）和 3-(4-羟苯基）-丙酸（4HPP）对肠道屏障损伤和结肠炎的保护作用。只有 4HPP 和 RES 能显著降低脂多糖（LPS）处理的肠道 Caco-2 细胞的细胞旁通透性和促炎细胞因子的分泌，这与紧密连接（TJ）蛋白的上调一致。此外，RES 和 4HPP 改善了结肠炎小鼠的肠道屏障功能障碍和结肠炎症，而 DHR 则没有。特别是，RES 和 4HPP 恢复了肠道 TJ 蛋白和 Muc2 的表达。其分子机制涉及腺苷单磷酸激活蛋白激酶（AMPK）介导的 CDX2 激活和 SIRT1/NF-κB 通路的调节。这些发现为理解 RES 对肠道屏障损伤和结肠炎的保护作用提供了新的见解。
