Glabridin inhibits osteoarthritis development by protecting chondrocytes against oxidative stress, apoptosis and promoting mTOR mediated autophagy

被引:31
作者
Dai, Jihang [1 ,2 ]
Zhang, Yaxin [1 ]
Chen, Deng [1 ]
Chen, Duoyun [1 ]
Li, Xiaolei [2 ]
Wang, Jingcheng [2 ]
Sun, Yu [2 ]
机构
[1] Dalian Med Univ, Dalian 116044, Liaoning, Peoples R China
[2] Yangzhou Univ, Dept Orthoped, Northern Jiangsu Peoples Hosp, Yangzhou, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Glabridin; Osteoarthritis; Oxidative stress; Apoptosis; Autophagy;
D O I
10.1016/j.lfs.2020.118992
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Osteoarthritis (OA) is a common chronic degenerative disease that affects the elderly. Thus far, no pharmacological therapy approved by regulators has shown a convincing effect on OA. Glabridin, a small molecule, is a well-known and powerful natural antioxidant, which has a strong scavenging effect on free radicals. This study attempted to explore the role and underlying mechanisms of Glabridin on OA both in vitro and in vivo. In the in vitro study, Glabridin was found to increase the expression levels of extracellular matrix (ECM) related genes, Collagen II, Aggrecan (ACAN), SRY-box 9 (SOX9) and proteoglycan 4 (PRG4). Moreover, Glabridin was observed to significantly reduce the level of oxidative stress in OA chondrocytes while effectively reducing the apoptosis of chondrocytes. Glabridin was also found to significantly increase the autophagy of human OA chondrocytes. During the in vivo study, intraarticular injection of Glabridin was observed to alleviate OA progression and protect chondrocytes against apoptosis following anterior cruciate ligament transection (ACLT) in rats. Furthermore, the mammalian target of rapamycin (mTOR) mediated autophagy was identified as one of the potential mediators of Glabridin activity. Overall, Glabridin protects articular cartilage from damage in rats with OA by protecting chondrocytes against oxidative stress, apoptosis and promoting mTOR mediated autophagy.
引用
收藏
页数:12
相关论文
共 50 条
[31]   Liquiritigenin protects against arsenic trioxide-induced liver injury by inhibiting oxidative stress and enhancing mTOR-mediated autophagy [J].
Zhang, Muqing ;
Xue, Yucong ;
Zheng, Bin ;
Li, Li ;
Chu, Xi ;
Zhao, Yang ;
Wu, Yongchao ;
Zhang, Jianping ;
Han, Xue ;
Wu, Zhonglin ;
Chu, Li .
BIOMEDICINE & PHARMACOTHERAPY, 2021, 143
[32]   Tetrahedral Framework Nucleic Acid Inhibits Chondrocyte Apoptosis and Oxidative Stress through Activation of Autophagy [J].
Shi, Sirong ;
Tian, Taoran ;
Li, Yanjing ;
Xiao, Dexuan ;
Zhang, Tao ;
Gong, Ping ;
Lin, Yunfeng .
ACS APPLIED MATERIALS & INTERFACES, 2020, 12 (51) :56782-56791
[33]   Hydrogen sulfide inhibits endoplasmic reticulum stress through the GRP78/mTOR pathway in rat chondrocytes subjected to oxidative stress [J].
Wu, Jianjun ;
Yang, Fan ;
Zhang, Xin ;
Chen, Guanghua ;
Zou, Jilong ;
Yin, Li ;
Yang, Dawei .
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2021, 47 (04)
[34]   Inhibition of HDAC6 by Tubastatin A reduces chondrocyte oxidative stress in chondrocytes and ameliorates mouse osteoarthritis by activating autophagy [J].
Shen, Zhonghai ;
Ji, Kang ;
Cai, Zhenhai ;
Huang, Chenglong ;
He, Xiaojun ;
Xu, Hongwei ;
Chen, Gang .
AGING-US, 2021, 13 (07) :9820-9837
[35]   Anti-Apoptosis and Autophagy Effects of Melatonin Protect Rat Chondrocytes against Oxidative Stress via Regulation of AMPK/Foxo3 Pathways [J].
Chen, Zhaoxun ;
Zhao, Chen ;
Liu, Pengcheng ;
Huang, Haohan ;
Zhang, Shuhong ;
Wang, Xiaoqing .
CARTILAGE, 2021, 13 (2_SUPPL) :1041S-1053S
[36]   Effects of quercetin on apoptosis and extracellular matrix degradation of chondrocytes induced by oxidative stress-mediated pyroptosis [J].
Wang, Qing ;
Ying, Lujing ;
Wei, Bing ;
Ji, Yikui ;
Xu, Yi .
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, 2022, 36 (02)
[37]   Silencing UHRF1 enhances cell autophagy to prevent articular chondrocytes from apoptosis in osteoarthritis through PI3K/AKT/mTOR signaling pathway [J].
Shi, Xiaojuan ;
Han, Lei ;
Sun, Tianshu ;
Zhang, Feng ;
Ji, Shiying ;
Zhang, Min ;
Wang, Xiaoqing ;
Yang, Weihong .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2020, 529 (04) :1018-1024
[38]   Investigating the Effects of Simultaneous Administration of Melatonin and Atorvastatin against High Glucose-Induced Oxidative Stress and Apoptosis in Cultured Chondrocytes [J].
Mehrzadi, Saeed ;
Safa, Majid ;
Hosseinzadeh, Azam .
CURRENT RHEUMATOLOGY REVIEWS, 2024,
[39]   An updated review of mechanistic potentials of melatonin against cancer: pivotal roles in angiogenesis, apoptosis, autophagy, endoplasmic reticulum stress and oxidative stress [J].
Saeed Mehrzadi ;
Mohammad Hossein Pourhanifeh ;
Alireza Mirzaei ;
Farid Moradian ;
Azam Hosseinzadeh .
Cancer Cell International, 21
[40]   An updated review of mechanistic potentials of melatonin against cancer: pivotal roles in angiogenesis, apoptosis, autophagy, endoplasmic reticulum stress and oxidative stress [J].
Mehrzadi, Saeed ;
Pourhanifeh, Mohammad Hossein ;
Mirzaei, Alireza ;
Moradian, Farid ;
Hosseinzadeh, Azam .
CANCER CELL INTERNATIONAL, 2021, 21 (01)