Gentiopicroside Alleviates Atherosclerosis by Suppressing Reactive Oxygen Species-Dependent NLRP3 Inflammasome Activation in Vascular Endothelial Cells via SIRT1/Nrf2 Pathway  

作　　者：LI Zhu-qing ZHANG Feng LI Qi WANG Li SUN Xiao-qiang LI Chao YIN Xue-mei LIU Chun-lei WANG Yan-xin DU Xiao-yu LU Cheng-zhi 

机构地区：[1]Department of Cardiology,Tianjin First Central Hospital,Tianjin,300192,China [2]The First Central Clinical School,Tianjin Medical University,Tianjin,300070,China [3]Department of Cardiology,The First College of Clinical Medical Science,China Three Gorges University&Yichang Central People’s Hospital,Yichang,Hubei Province,443003,China [4]School of Medicine,Nankai University,Tianjin,300071,China

出　　处：《Chinese Journal of Integrative Medicine》2025年第2期118-130,共13页中国结合医学杂志(英文版)

基　　金：Supported by the National Natural Science Foundation of China(No.82300445);the Natural Science Foundation of Tianjin(No.22JCQNJC01130);the Medical Health Science and Technology Project of Tianjin Municipal Health Commission(No.TJWJ2023QN026)。

摘　　要：Objective:To evaluate the protective effects of gentiopicroside(GPS)against reactive oxygen species(ROS)-induced NOD-like receptor family,pyrin domain containing 3(NLRP3)inflammasome activation in endothelial cells,aiming to reduce atherosclerosis.Methods:Eight-week-old male ApoE-deficient mice were randomly divided into 2 groups(n=10 per group):the vehicle group and the GPS treatment group.Both groups were fed a high-fat diet for 16 weeks.GPS(40 mg/kg per day)was administered by oral gavage to the GPS group,while the vehicle group received an equivalent volume of the vehicle solution.At the end of the treatment,blood and aortic tissues were collected for assessments of atherosclerosis,lipid profiles,oxidative stress,and molecular expressions related to NLRP3 inflammasome activation,ROS production,and apoptosis.Additionally,in vitro experiments on human aortic endothelial cells treated with oxidized low-density lipoprotein(ox-LDL)were conducted to evaluate the effects of GPS on NLRP3 inflammasome activation,pyroptosis,apoptosis,and ROS production,specifically examining the role of the sirtuin 1(SIRT1)/nuclear factor erythroid 2-related factor 2(Nrf2)pathway.SIRT1 and Nrf2 inhibitors were used to confirm the pathway's role.Results:GPS treatment significantly reduced atherosclerotic lesions in the en face aorta(P<0.01),as well as in the thoracic and abdominal aortic regions,and markedly decreased sinus lesions within the aortic root(P<0.05 or P<0.01).Additionally,GPS reduced oxidative stress markers and proinflammatory cytokines,including interleukin(IL)-1βand IL-18,in lesion areas(P<0.05,P<0.01).In vitro,GPS inhibited ox-LDL-induced NLRP3 activation,as evidenced by reduced NLRP3(P<0.01),apoptosis-associated speck-like protein containing a CARD,cleaved-caspase-1,and cleavedgasdermin D expressions(all P<0.01).GPS also decreased ROS production,apoptosis,and pyroptosis,with the beneficial effects being significantly reversed by SIRT1 or Nrf2 inhibitors.Conclusion:GPS exerts an antiatherogenic effect by inhibiting ROS

关 键 词：endothelial dysfunction GENTIOPICROSIDE NLRP3 inflammasome SIRT1 nuclear factor erythroid 2-related factor 2 Chinese medicine 

分 类 号：R285[医药卫生—中药学]