Dragon’s blood attenuates LPS-induced intestinal epithelial barrier dysfunction via upregulation of FAK-DOCK180-Rac1-WAVE2-Arp3 and downregulation of TLR4/NF-κB signaling pathways

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL Journal of Natural Medicines Pub Date : 2024-07-17 DOI:10.1007/s11418-024-01824-z

Huayan Liu, Ranran Yan, Yongzhi Li, Jiaping Wang, Yulin Deng, Yujuan Li

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Abstract

Inflammation-induced intestinal epithelial barrier (IEB) dysfunction is one of the important reasons for the occurrence and development of intestinal inflammatory-related diseases, including ulcerative colitis (UC), Crohn’s disease and necrotizing enterocolitis (NEC). Dragon’s blood (DB) is a traditional Chinese medicine and has been clinically used to treat UC. However, the protective mechanism of DB on intestinal inflammatory-related diseases has still not been elucidated. The present study aimed to explore the protection mechanism of DB on IEB dysfunction in rat ileum and human colorectal adenocarcinoma cells (Caco-2)/human umbilical vein endothelial cells (HUVECs) coculture system induced by lipopolysaccharide (LPS). DB could ameliorate rat ileum mucosa morphological injury, reduce the accumulation of lipid-peroxidation products and increase the expression of junction proteins. DB also alleviated LPS-induced Caco-2 cells barrier integrity destruction in Caco-2/ HUVECs coculture system, leading to increased trans-endothelial electrical resistance (TEER), reduced cell permeability, and upregulation of expressions of F-actin and junction proteins. DB contributed to the assembly of actin cytoskeleton by upregulating the FAK-DOCK180-Rac1-WAVE2-Arp3 pathway and contributed to the formation of intercellular junctions by downregulating TLR4-MyD88-NF-κB pathway, thus reversing LPS-induced IEB dysfunction. These novel findings illustrated the potential protective mechanism of DB on intestinal inflammatory-related diseases and might be useful for further clinical application of DB.

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龙血通过上调FAK-DOCK180-Rac1-WAVE2-Arp3和下调TLR4/NF-κB信号通路，减轻LPS诱导的肠上皮屏障功能障碍。

炎症引起的肠上皮屏障（IEB）功能障碍是溃疡性结肠炎（UC）、克罗恩病和坏死性小肠结肠炎（NEC）等肠道炎症相关疾病发生和发展的重要原因之一。龙血（DB）是一种传统中药，已被临床用于治疗溃疡性结肠炎。然而，龙血竭对肠道炎症相关疾病的保护机制仍未阐明。本研究旨在探讨DB对大鼠回肠和脂多糖（LPS）诱导的人大肠腺癌细胞（Caco-2）/人脐静脉内皮细胞（HUVECs）共培养系统中IEB功能障碍的保护机制。DB能改善大鼠回肠粘膜的形态损伤，减少脂质过氧化产物的积累，增加连接蛋白的表达。在 Caco-2/ HUVECs 共培养系统中，DB 还能缓解 LPS 诱导的 Caco-2 细胞屏障完整性破坏，导致跨内皮电阻（TEER）增加、细胞通透性降低以及 F-肌动蛋白和连接蛋白表达上调。DB 通过上调 FAK-DOCK180-Rac1-WAVE2-Arp3 通路促进肌动蛋白细胞骨架的组装，并通过下调 TLR4-MyD88-NF-κB 通路促进细胞间连接的形成，从而逆转 LPS 诱导的 IEB 功能障碍。这些新发现说明了 DB 对肠道炎症相关疾病的潜在保护机制，可能有助于 DB 的进一步临床应用。

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来源期刊

Journal of Natural Medicines 医学-药学

CiteScore

6.90

自引率

3.00%

发文量

审稿时长

1.7 months

期刊介绍： The Journal of Natural Medicines is an international journal publishing original research in naturally occurring medicines and their related foods and cosmetics. It covers: -chemistry of natural products -biochemistry of medicinal plants -pharmacology of natural products and herbs, including Kampo formulas and traditional herbs -botanical anatomy -cultivation of medicinal plants. The journal accepts Original Papers, Notes, Rapid Communications and Natural Resource Letters. Reviews and Mini-Reviews are generally invited.