Angelicin attenuates sepsis-associated acute liver injury via p38 MAPK inhibition and NF-kB-mediated Nrf2/Keap1 activation to suppress inflammation and oxidative stressOA
Sepsis-associated acute liver injury(SALl)is a frequent and clinically severe complication of sepsis,in which inflammatory responses and oxidative stress are involved.Angelicin(ANG),one of the main active components in the traditional Chinese medicine Psoralea corylifolia Linn.,has anti-inflammatory and antioxidant bioactivities.In this study,the protective effect of ANG on SALl and its specific mechanism are investigated by establishing a mouse model of caecal ligation and puncture(CLP)-induced SALI and an in vitro sepsis model in LPS-stimulated AML12 cells.These results show that ANG can alleviate liver injury and improve liver function in SALI mice.ANG decreases the mRNA expression levels of the pro-inflammatory factors Il-1β,Il-6,and Tnf-αand increases the mRNA expression level of the anti-inflammatory factor Il-10,which suggests its anti-inflammatory effects.The results of the biochemical kit assay and DHE staining show that ANG can decrease the levels of MDA and ROS and increase the level of GSH and the activities of CAT and SOD,which suggests that ANG has antioxidant effects.Mechanistically,ANG exerts anti-inflammatory effects by inhibiting the NF-kB and p38 MAPK pathways and exerting antioxidant effects by activating the Nrf2/Keap1 pathway.Additionally,cell transfection experiments indicate that activation of the Nrf2/Keap1 pathway by ANG may depend on the inhibition of the NF-kB pathway.In conclusion,ANG attenuates SALI by inhibiting the NF-kB and p38 MAPK pathways,thereby activating the Nrf2/Keap1 pathway and making it a promising therapeutic intervention for SALI.
Enzhuang Pan;Huilin Sun;Shasha Zhang;Jun Wang;Yedan Liu;Feibiao Wang;Jing Xia;Yingjia Qian;Xiaolong Xu;Jingquan Dong
Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center,Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening,College of Pharmacy,Jiangsu Ocean University,Lianyungang 222005,ChinaSchool of Medicine,Nantong University Xinglin College,Nantong 226236,ChinaJiangsu Marine Pharmaceutical Resources Development Engineering Research Center,Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening,College of Pharmacy,Jiangsu Ocean University,Lianyungang 222005,ChinaJiangsu Marine Pharmaceutical Resources Development Engineering Research Center,Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening,College of Pharmacy,Jiangsu Ocean University,Lianyungang 222005,ChinaJiangsu Marine Pharmaceutical Resources Development Engineering Research Center,Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening,College of Pharmacy,Jiangsu Ocean University,Lianyungang 222005,ChinaJiangsu Marine Pharmaceutical Resources Development Engineering Research Center,Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening,College of Pharmacy,Jiangsu Ocean University,Lianyungang 222005,ChinaJiangsu Marine Pharmaceutical Resources Development Engineering Research Center,Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening,College of Pharmacy,Jiangsu Ocean University,Lianyungang 222005,ChinaJiangsu Marine Pharmaceutical Resources Development Engineering Research Center,Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening,College of Pharmacy,Jiangsu Ocean University,Lianyungang 222005,ChinaDepartment of Pharmacy,Lianyungang Affiliated Hospital of Nanjing University of Chinese Medicine,Lianyungang 222004,ChinaJiangsu Marine Pharmaceutical Resources Development Engineering Research Center,Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening,College of Pharmacy,Jiangsu Ocean University,Lianyungang 222005,China
医药卫生
angelicinsepsis-associated acute liver injuryinflammationoxidative stress
《Acta Biochimica et Biophysica Sinica》 2026 (6)
P.1387-1401,15
supported by the grants from the Postgraduate Research&Practice Innovation Program of Jiangsu Ocean University(No.KYCX2024-18)the Lianyungang Traditional Chinese Medicine Science and Technology Development Plan Project(No.YB202203)the Science and Technology Funds of Kangda College,Nanjing Medical University(KD2024KYJJ085)the Jiangsu Society of Traditional Chinese Medicine Research Project(CYTF2024063)the Jiangsu Provincial Pharmaceutical Association-Aosaikang Hospital Pharmaceutical Research Fund Project(A202435)the Priority Academic Program Development of Jiangsu Higher Education Institutions of China.
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