TY - JOUR
T1 - 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
AU - Liu, Huayan
AU - Yan, Ranran
AU - Li, Yongzhi
AU - Wang, Jiaping
AU - Deng, Yulin
AU - Li, Yujuan
N1 - Publisher Copyright:
© The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy 2024.
PY - 2024/9
Y1 - 2024/9
N2 - 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. Graphical abstract: (Figure presented.)
AB - 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. Graphical abstract: (Figure presented.)
KW - Dragon’s blood
KW - FAK/DOCK180/Rac1/WAVE2/Arp3 signaling pathway
KW - Intestinal epithelial barrier
KW - TLR4/MyD88/NF-κB signaling pathway
UR - http://www.scopus.com/inward/record.url?scp=85198713083&partnerID=8YFLogxK
U2 - 10.1007/s11418-024-01824-z
DO - 10.1007/s11418-024-01824-z
M3 - Comment/debate
AN - SCOPUS:85198713083
SN - 1340-3443
VL - 78
SP - 1013
EP - 1028
JO - Journal of Natural Medicines
JF - Journal of Natural Medicines
IS - 4
ER -