膳食原儿茶酸通过靶向 Rho 相关蛋白激酶重新分布紧密连接蛋白以改善肠道屏障功能,Food & Function

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膳食原儿茶酸通过靶向 Rho 相关蛋白激酶重新分布紧密连接蛋白以改善肠道屏障功能
Food & Function ( IF 5.1 ) Pub Date : 2023-04-25 , DOI: 10.1039/d3fo00605k
Bo Ram So ₁ , San Kim ₁ , Se Hyeon Jang ₁ , Min Jeong Kim ₁ , Jeong Jae Lee ₁ , Soo Rin Kim _{1,

2} , Sung Keun Jung _{1,

2}

Affiliation

炎症性肠病 (IBD) 在全球范围内不断增加，由肠屏障功能障碍引起。尽管原儿茶酸 (PCA) 对结肠炎具有保护作用，但其对肠道屏障功能的贡献背后的分子机制仍然未知。跨上皮电阻 (TEER) 和 FITC-葡聚糖通透性测量表明 PCA 抑制脂多糖 (LPS) 和肿瘤坏死因子 (TNF)-α 诱导的肠道通透性增加；zonula occludens (ZO)-1 和 claudin-2 的重新分布在分化的 Caco-2 细胞的上皮细胞膜中也受到抑制。PCA 被发现直接结合 Rho 相关的卷曲螺旋蛋白激酶 (ROCK)，随后抑制肌球蛋白轻链 (MLC) 磷酸化。值得注意的是，PCA 与 ROCK 的结合程度与 Y27632 相似，选择性 ROCK 抑制剂。给 C57BL/6 小鼠口服 PCA（每天每千克 5 或 25 毫克）可减轻 3% 葡聚糖硫酸钠 (DSS) 诱导的结肠炎症状，包括结肠长度缩短、肠屏障结构破坏和促炎细胞因子表达增加，例如白细胞介素 (IL)-1β、TNF-α 和 IL-6。此外，口服 PCA 可抑制 DSS 诱导的 ZO-1 和 claudin-2/4 在小鼠结肠膜组分中的重新分布。因此，PCA 可作为一种有前途的营养品，通过维持肠道屏障功能来改善肠道健康和减轻 IBD 并增加促炎细胞因子的表达，例如白细胞介素 (IL)-1β、TNF-α 和 IL-6。此外，口服 PCA 可抑制 DSS 诱导的 ZO-1 和 claudin-2/4 在小鼠结肠膜组分中的重新分布。因此，PCA 可作为一种有前途的营养品，通过维持肠道屏障功能来改善肠道健康和减轻 IBD 并增加促炎细胞因子的表达，例如白细胞介素 (IL)-1β、TNF-α 和 IL-6。此外，口服 PCA 可抑制 DSS 诱导的 ZO-1 和 claudin-2/4 在小鼠结肠膜组分中的重新分布。因此，PCA 可作为一种有前途的营养品，通过维持肠道屏障功能来改善肠道健康和减轻 IBD体外和体内。

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Dietary protocatechuic acid redistributes tight junction proteins by targeting Rho-associated protein kinase to improve intestinal barrier function

Inflammatory bowel disease (IBD) is continuously increasing globally and caused by intestinal barrier dysfunction. Although protocatechuic acid (PCA) has a protective effect on colitis, the molecular mechanisms underlying its contribution to intestinal barrier function remain unknown. Transepithelial electrical resistance (TEER) and FITC-dextran permeability measurements reveled that PCA suppresses lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-α-induced increase in intestinal permeability; zonula occludens (ZO)-1 and claudin-2 redistribution was also suppressed in the epithelial cell membranes of differentiated Caco-2 cells. PCA was found to directly bind Rho-associated coiled-coil containing protein kinase (ROCK), subsequently suppressing myosin light chain (MLC) phosphorylation. Notably, PCA binds ROCK to a similar degree as Y27632, a selective ROCK inhibitor. Orally administering PCA (5 or 25 mg per kg per day) to C57BL/6 mice alleviated the 3% dextran sulfate sodium (DSS)-induced colitis symptoms including reduced colon length, disrupted intestinal barrier structure, and increased proinflammatory cytokines expressions, such as interleukin (IL)-1β, TNF-α, and IL-6. Furthermore, orally administering PCA suppressed DSS-induced ZO-1 and claudin-2/4 redistribution in mice colon membrane fractions. Therefore, PCA may serve as a promising nutraceutical to improve gut health and alleviate IBD by maintaining intestinal barrier function in vitro and in vivo.

更新日期：2023-04-25

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