Department of Nutrition, University of California, Davis, CA, USA; Department of Environmental Toxicology, University of California, Davis, CA, USA.
Pharmanex Research, NSE Products, Inc., Provo, UT, USA.
Free Radic Biol Med. 2022 Aug 1;188:71-82. doi: 10.1016/j.freeradbiomed.2022.06.006. Epub 2022 Jun 9.
Consumption of high fat diets (HFD) mimics a modern or "Western style" diet pattern and can impair intestinal barrier integrity, leading to endotoxemia and associated unhealthy conditions. This study investigated if supplementation with an anthocyanin (cyanidin and delphinidin glucosides)-rich extract (CDRE) could revert or mitigate HFD-induced alterations of colonic physiology in part through the regulation of Toll-Like Receptor 4 (TLR-4)- and redox-regulated signaling. C57BL/6J male mice were fed for 4 weeks with a control or an HFD. Then, mice were divided in four groups fed either control or HFD, or these diets supplemented with CDRE for the subsequent 4 weeks. After 8 weeks on the HFD we observed in the colon: i) disruption of tight junction structure and function; ii) increased TLR-4 expression; iii) increased NADPH oxidase NOX1 expression, and iv) activation of redox-sensitive and TLR-4-triggered pathways, i.e. NF-κB, ERK1/2, JNK1/2, PI3K/Akt. All these events were prevented or reverted by CDRE supplementation. Supporting the relevance of CDRE-mediated downregulation of TLR-4 on its colon beneficial effect; in vitro (Caco-2 cell monolayers), cyanidin, delphinidin and their metabolites protocatechuic and gallic acid, mitigated lipopolysaccharide (LPS)-induced monolayer permeabilization by restoring tight junction structure and dynamics and preventing lipid/protein oxidation. The CDRE also mitigated HFD-mediated alterations in parameters of goblet cell differentiation and function, including the downregulation of markers of goblet cell differentiation (Klf4), and intestinal mucosa healing (Tff3). Results show that a short-term supplementation with cyanidin and delphinidin, protect from HFD-induced alterations in colon physiology in part through the modulation of TLR-4- and redox-regulated signaling.
高脂肪饮食（HFD）的摄入模拟了现代或“西式”饮食模式，可损害肠道屏障完整性，导致内毒素血症和相关的不健康状况。本研究旨在探讨是否通过调节 Toll 样受体 4（TLR-4）和氧化还原调节信号，富含矢车菊素和天竺葵素葡萄糖苷的花色苷（CDRE）补充剂可以逆转或减轻 HFD 引起的结肠生理改变。C57BL/6J 雄性小鼠用对照或 HFD 喂养 4 周。然后，将小鼠分为四组，分别用对照或 HFD 喂养，或用 CDRE 补充这些饮食 4 周。在 HFD 喂养 8 周后，我们在结肠中观察到：i）紧密连接结构和功能受损；ii）TLR-4 表达增加；iii）NADPH 氧化酶 NOX1 表达增加；iv）氧化还原敏感和 TLR-4 触发途径（NF-κB、ERK1/2、JNK1/2、PI3K/Akt）被激活。所有这些事件都被 CDRE 补充所预防或逆转。支持 CDRE 介导的 TLR-4 下调对其结肠有益作用的相关性；在体外（Caco-2 细胞单层），矢车菊素、天竺葵素及其代谢物原儿茶酸和没食子酸通过恢复紧密连接结构和动力学以及防止脂质/蛋白质氧化，减轻脂多糖（LPS）诱导的单层通透性。CDRE 还减轻了 HFD 介导的杯状细胞分化和功能参数的改变，包括杯状细胞分化标志物（Klf4）和肠黏膜愈合（Tff3）的下调。结果表明，短期补充矢车菊素和天竺葵素可通过调节 TLR-4 和氧化还原调节信号来防止 HFD 引起的结肠生理改变。
