Gentiopicroside Alleviates Atherosclerosis by Suppressing Reactive Oxygen Species-Dependent NLRP3 Inflammasome Activation in Vascular Endothelial Cells via SIRT1/Nrf2 Pathway.
10.1007/s11655-024-4206-6
- Author:
Zhu-Qing LI
1
;
Feng ZHANG
2
;
Qi LI
3
;
Li WANG
1
;
Xiao-Qiang SUN
1
;
Chao LI
1
;
Xue-Mei YIN
1
;
Chun-Lei LIU
4
;
Yan-Xin WANG
2
;
Xiao-Yu DU
2
;
Cheng-Zhi LU
5
Author Information
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.
5. Department of Cardiology, Tianjin First Central Hospital, Tianjin, 300192, China. 5020200072@nankai.edu.cn.
- Publication Type:Journal Article
- Keywords:
Chinese medicine;
NLRP3 inflammasome;
SIRT1;
endothelial dysfunction;
gentiopicroside;
nuclear factor erythroid 2-related factor 2
- MeSH:
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*;
Reactive Oxygen Species/metabolism*;
Iridoid Glucosides/therapeutic use*;
NF-E2-Related Factor 2/metabolism*;
Animals;
Atherosclerosis/metabolism*;
Inflammasomes/drug effects*;
Male;
Sirtuin 1/metabolism*;
Signal Transduction/drug effects*;
Humans;
Endothelial Cells/pathology*;
Mice;
Oxidative Stress/drug effects*;
Apoptosis/drug effects*;
Lipoproteins, LDL;
Mice, Inbred C57BL
- From:
Chinese journal of integrative medicine
2025;31(2):118-130
- CountryChina
- Language:English
-
Abstract:
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)-1 β and 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 cleaved-gasdermin 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-dependent NLRP3 inflammasome activation via the SIRT1/Nrf2 pathway.
