细胞外基质
粘附
细胞生物学
炎症
细胞外
基质(化学分析)
化学
免疫学
生物
色谱法
有机化学
作者
Heng Liu,Henghui Xu,Heyang Sun,Honglin Xu,Jingjing Han,Limin Zhao,Xiaohan Li,XiuXiu Sun,Xinxin Dong,Run Xu,Zhouxiu Chen,Menghan Du,Pingping Tang,Yongchao Chen,Lin Yuan,Yong Zhang,Weina Han,Xin Liu
标识
DOI:10.1016/j.ejphar.2023.175803
摘要
Peritoneal adhesion is a common abdominal surgical complication that induces abdominal haemorrhage, intestinal obstruction, infertility, and so forth. The high morbidity and recurrence rate of this disease indicate the need for novel therapeutic approaches. Here, we revealed the protective roles of tetrahydroberberrubine (THBru), a novel derivative of berberine (BBR), in preventing peritoneal adhesion and identified its underlying mechanism in vivo and in vitro. Abrasive surgery was used to create a peritoneal adhesion rat model. We found that THBru administration markedly ameliorated peritoneal adhesion, as indicated by a lowered adhesion score and ameliorated caecal tissue damage. By comparison, THBru exhibited more potent anti-adhesion effects than BBR at the same dose. Mechanistically, THBru inhibited inflammation and extracellular matrix (ECM) accumulation in the microenvironment of adhesion tissue. THBru suppressed the expression of inflammatory cytokines including interleukin-1β (IL-1β), IL-6, transforming growth factor β (TGF-β), tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1), by regulating the transforming growth factor beta–activated kinase 1 (TAK1)/c-Jun N-terminal kinase (JNK) and TAK1/nuclear factor κB (NF-κB) signaling pathways. However, THBru promoted the activation of MMP-3 by directly blocking the TIMP-1 activation core and subsequently decreased collagen deposition. Taken together, this study identifies THBru as an effective anti-adhesion agent that regulates diverse mechanisms, thereby outlining its potential therapeutic implications for the treatment of peritoneal adhesion.
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