Guangtao Pan , Yanran Wu , Yuhan Liu , Fangyuan Zhou , Sen Li , Shenglan Yang
{"title":"Dachengqi decoction ameliorates sepsis-induced liver injury by inhibiting the TGF-β1/Smad3 pathways","authors":"Guangtao Pan , Yanran Wu , Yuhan Liu , Fangyuan Zhou , Sen Li , Shenglan Yang","doi":"10.1016/j.jtcme.2023.09.001","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Sepsis-induced acute liver injury (ALI) is a major contributor to mortality in septic patients. Exploring the pathogenesis and developing effective treatment strategies for sepsis-induced ALI is critical for improving patient outcomes. Dachengqi decoction (DCQD), which is a classic Chinese herbal medicine, has been shown to possess potent anti-inflammatory properties. However, the protective effects and underlying mechanisms of DCQD against sepsis-induced ALI remain unclear. This study aimed to investigate the protective effect of DCQD on sepsis-induced ALI and elucidate the involvement of the TGF-1β/Smad3 pathways.</p></div><div><h3>Methods</h3><p>A septic mouse model was established using caecal ligation and puncture (CLP) to evaluate the protective effect of DCQD on sepsis-induced ALI in vivo. An in vitro cellular inflammation model was established using LPS-stimulated LO2 cells to further investigate the underlying mechanism.</p></div><div><h3>Results</h3><p>DCQD (2.5, 5.0, and 10.0 g/kg body weight) was administered twice daily for 2 days and exerted a dose-dependent protective effect against sepsis-induced ALI. DCQD treatment significantly inhibited inappropriate inflammatory responses and oxidative stress in liver tissue. Moreover, DCQD maintained liver homeostasis by inhibiting hepatocyte apoptosis and improving sepsis-induced liver damage. In vivo and in vitro studies indicated that the TGF-β1/Smad3 signalling pathway played an important role in sepsis-induced ALI, and DCQD treatment significantly inhibited the activation of this pathway.</p></div><div><h3>Conclusions</h3><p>DCQD can effectively suppress excessive inflammatory responses and oxidative stress, leading to a substantial reduction in hepatocyte apoptosis in sepsis-induced ALI.</p></div>","PeriodicalId":3,"journal":{"name":"ACS Applied Electronic Materials","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2225411023000986/pdfft?md5=def899755182ac87462074234c9986d8&pid=1-s2.0-S2225411023000986-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Electronic Materials","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2225411023000986","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, ELECTRICAL & ELECTRONIC","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Sepsis-induced acute liver injury (ALI) is a major contributor to mortality in septic patients. Exploring the pathogenesis and developing effective treatment strategies for sepsis-induced ALI is critical for improving patient outcomes. Dachengqi decoction (DCQD), which is a classic Chinese herbal medicine, has been shown to possess potent anti-inflammatory properties. However, the protective effects and underlying mechanisms of DCQD against sepsis-induced ALI remain unclear. This study aimed to investigate the protective effect of DCQD on sepsis-induced ALI and elucidate the involvement of the TGF-1β/Smad3 pathways.
Methods
A septic mouse model was established using caecal ligation and puncture (CLP) to evaluate the protective effect of DCQD on sepsis-induced ALI in vivo. An in vitro cellular inflammation model was established using LPS-stimulated LO2 cells to further investigate the underlying mechanism.
Results
DCQD (2.5, 5.0, and 10.0 g/kg body weight) was administered twice daily for 2 days and exerted a dose-dependent protective effect against sepsis-induced ALI. DCQD treatment significantly inhibited inappropriate inflammatory responses and oxidative stress in liver tissue. Moreover, DCQD maintained liver homeostasis by inhibiting hepatocyte apoptosis and improving sepsis-induced liver damage. In vivo and in vitro studies indicated that the TGF-β1/Smad3 signalling pathway played an important role in sepsis-induced ALI, and DCQD treatment significantly inhibited the activation of this pathway.
Conclusions
DCQD can effectively suppress excessive inflammatory responses and oxidative stress, leading to a substantial reduction in hepatocyte apoptosis in sepsis-induced ALI.
背景脓毒症诱发的急性肝损伤(ALI)是导致脓毒症患者死亡的主要原因。探索脓毒症诱发急性肝损伤的发病机制并制定有效的治疗策略对于改善患者预后至关重要。大承气汤(DCQD)是一种经典中药,已被证明具有强大的抗炎特性。然而,大承气汤对脓毒症诱发的 ALI 的保护作用及其机制仍不清楚。本研究旨在探讨DCQD对脓毒症诱发的ALI的保护作用,并阐明TGF-1β/Smad3通路的参与作用。方法利用盲肠结扎术(CLP)建立脓毒症小鼠模型,评估DCQD对脓毒症诱发的ALI的体内保护作用。结果DCQD(2.5、5.0和10.0克/千克体重)每天给药两次,持续2天,对脓毒症诱发的ALI具有剂量依赖性保护作用。DCQD能明显抑制肝组织中不适当的炎症反应和氧化应激。此外,DCQD 还能抑制肝细胞凋亡,改善败血症引起的肝损伤,从而维持肝脏的稳态。体内和体外研究表明,TGF-β1/Smad3 信号通路在脓毒症诱发的 ALI 中发挥了重要作用,而 DCQD 治疗可显著抑制该通路的激活。