Andrographolide protects bone marrow mesenchymal stem cells against glucose and serum deprivation under hypoxia via the NRF2 signaling pathway

作者全名："Sun, Yanting; Xu, Hao; Tan, Bin; Yi, Qin; Liu, Huiwen; Chen, Tangtian; Xiang, Han; Wang, Rui; Xie, Qiumin; Tian, Jie; Zhu, Jing"

作者地址："[Sun, Yanting; Xu, Hao; Tan, Bin; Yi, Qin; Liu, Huiwen; Chen, Tangtian; Xiang, Han; Wang, Rui; Xie, Qiumin; Tian, Jie; Zhu, Jing] Chongqing Med Univ, Childrens Hosp, Res Inst,Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Dept Pediat,Chongqing Key Lab Pediat, Chongqing 400014, Peoples R China; [Xu, Hao] Chongqing Med Univ, Dept Clin Lab, Childrens Hosp, Chongqing, Peoples R China; [Tian, Jie] Chongqing Med Univ, Dept Cardiovasc Internal Med, Childrens Hosp, Chongqing, Peoples R China"

通信作者："Zhu, J (通讯作者)，Chongqing Med Univ, Childrens Hosp, Res Inst,Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Dept Pediat,Chongqing Key Lab Pediat, Chongqing 400014, Peoples R China."

来源：STEM CELL RESEARCH & THERAPY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000827899300003

JCR分区：Q1

影响因子：7.5

年份：2022

卷号：13

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：BMSCs; NRF2; Andrographolide; Apoptosis; Oxidative stress

摘要："Background Bone marrow mesenchymal stem cell (BMSCs) therapy is an important cell transplantation strategy in the regenerative medicine field. However, a severely ischemic microenvironment, such as nutrient depletion and hypoxia, causes a lower survival rate of transplanted BMSCs, limiting the application of BMSCs. Therefore, improving BMSCs viability in adverse microenvironments is an important means to improve the effectiveness of BMSCs therapy. Objective To illustrate the protective effect of andrographolide (AG) against glucose and serum deprivation under hypoxia (1% O-2) (GSDH)-induced cell injury in BMSCs and investigate the possible underlying mechanisms. Methods An in vitro primary rat BMSCs cell injury model was established by GSDH, and cellular viability, proliferation and apoptosis were observed after AG treatment under GSDH. Reactive oxygen species levels and oxidative stress-related genes and proteins were measured by flow cytometry, RT-qPCR and Western blotting. Mitochondrial morphology, function and number were further assessed by laser confocal microscopy and flow cytometry. Results AG protected BMSCs against GSDH-induced cell injury, as indicated by increases in cell viability and proliferation and mitochondrial number and decreases in apoptosis and oxidative stress. The metabolic status of BMSCs was changed from glycolysis to oxidative phosphorylation to increase the ATP supply. We further observed that the NRF2 pathway was activated by AG, and treatment of BMSCs with a specific NRF2 inhibitor (ML385) blocked the protective effect of AG. Conclusion Our results suggest that AG is a promising agent to improve the therapeutic effect of BMSCs."

基金机构："National Natural Science Foundation of China [81700250, 81670270]"

基金资助正文：This work was supported by the National Natural Science Foundation of China (Grant Numbers 81700250 and 81670270).