迷迭香酸通过调节肠道菌群,缓解肠道炎症损伤,抑制内质网应激和肠道平滑肌收缩异常。
Rosmarinic acid alleviates intestinal inflammatory damage and inhibits endoplasmic reticulum stress and smooth muscle contraction abnormalities in intestinal tissues by regulating gut microbiota.
发表日期:2023 Aug 18
作者:
Kan Li, Jiawei Wu, Shuang Xu, Xueying Li, Yanhe Zhang, Xue-Jiao Gao
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
宿主-细菌相互作用在炎症性肠病(IBD)中起着关键作用。肠道菌群失调可能导致肠道病理变化。迷迭香酸(RA)是一种天然酚酸化合物,具有抗氧化、抗癌、抗炎、抗细胞凋亡、抗纤维化和抗细菌活性,在急性IBD中具有缓解效果。我们建立了小鼠体内模型,并进行组织学染色以直接观察RA对肠道的改变。通过16S rRNA高通量测序观察了RA对小鼠肠道菌群的影响,通过qPCR和Western blot检测了RA对肠道作用机制的影响。结果显示RA对肠道具有显著的保护作用。RA上调了乳酸杆菌约翰逊菌(Lactobacillus johnsonii)和鼠菌株阿尔若米土古菌(Candidatus Arthromitus sp SFB-mouse-NL)的丰度,下调了广谱双歧杆菌(Bifidobacterium pseudolongum)、大肠埃希氏菌(Escherichia coli)和拉贡布斯汀肠杆菌(Romboutsia ilealis)的丰度。RA降调了ROCK,RhoA,CaM,MLC,MLCK,ZEB1,ZO-1,ZO-2,occludin,E-cadherin,IL-1β,IL-6,TNF-α,GRP78,PERK,IRE1,ATF6,CHOP,Caspase12,Caspase9,Caspase3,Bax,Cytc,RIPK1,RIPK3,MLKL的表达,并上调了IL-10和Bcl-2的表达。这些结果显示RA通过修复肠道菌群失调、减轻内质网应激、抑制细胞死亡和纠正平滑肌收缩调节失常,从而抑制了紧密连接损伤引起的炎症。本研究结果揭示了RA可以通过调节肠道菌群对小鼠小肠具有保护作用。重要性炎症性肠病(IBD)是一种慢性、反复发作的胃肠系统障碍。本研究探究了迷迭香酸对肠道的保护作用。结果显示RA在减少炎症损伤、内质网应激、平滑肌收缩异常和调节肠道菌群紊乱方面具有效果。
The host-bacterial interactions play the key role in inflammatory bowel disease (IBD). Dysbiosis of the intestinal flora can lead to pathological changes in the intestine. Rosmarinic acid (RA) is a natural phenolic acid compound with antioxidant, anti-cancer, anti-inflammatory, anti-apoptotic, anti-fibrotic, and anti-bacterial activities that has a palliative effect on acute IBD. We have established an in vivo model for mice. Histological staining was performed to directly observe RA alterations in the intestinal tract. The alteration of RA on mouse intestinal flora was observed by 16S rRNA high-throughput sequencing, and the effect of RA on intestinal mechanism of action was detected by qPCR and western blot. The results showed that RA had a significant protective effect on the intestine. RA upregulated the abundance of Lactobacillus johnsonii and Candidatus Arthromitus sp SFB-mouse-NL and downregulated the abundance of Bifidobacterium pseudolongum, Escherichia coli, and Romboutsia ilealis. RA downregulated the expressions of ROCK, RhoA, CaM, MLC, MLCK, ZEB1, ZO-1, ZO-2, occludin, E-cadherin, IL-1β, IL-6, TNF-α, GRP78, PERK, IRE1, ATF6, CHOP, Caspase12, Caspase9, Caspase3, Bax, Cytc, RIPK1, RIPK3, MLKL, and upregulated the expression of IL-10 and Bcl-2. These results displayed that RA inhibited the inflammation, which is caused by tight junction damage, by repairing intestinal flora dysbiosis, relieved endoplasmic reticulum stress, inhibited cell death, and corrected smooth muscle contractile dysregulation. The results of this study revealed RA could have a protective effect on the small intestine of mice by regulating intestinal flora. IMPORTANCE Inflammatory bowel disease (IBD) is a chronic, relapsing, remitting disorder of the gastrointestinal system. In this study, we investigated the protective effects of rosmarinic acid on the intestinal tract. The results showed that RA was effective in reducing inflammatory damage, endoplasmic reticulum stress, smooth muscle contraction abnormalities, and regulating intestinal flora disorders.