PMID- 33417956
OWN - NLM
STAT- MEDLINE
DCOM- 20210305
LR  - 20240226
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 268
DP  - 2021 Mar 1
TI  - Glabridin inhibits osteoarthritis development by protecting chondrocytes against 
      oxidative stress, apoptosis and promoting mTOR mediated autophagy.
PG  - 118992
LID - S0024-3205(20)31752-5 [pii]
LID - 10.1016/j.lfs.2020.118992 [doi]
AB  - 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.
CI  - Copyright (c) 2020. Published by Elsevier Inc.
FAU - Dai, Jihang
AU  - Dai J
AD  - Dalian Medical University, Dalian 116044, Liaoning, China; Department of 
      Orthopedics, Northern Jiangsu People's Hospital Affiliated to Yangzhou 
      University, Yangzhou, Jiangsu, China.
FAU - Zhang, Yaxin
AU  - Zhang Y
AD  - Dalian Medical University, Dalian 116044, Liaoning, China.
FAU - Chen, Deng
AU  - Chen D
AD  - Dalian Medical University, Dalian 116044, Liaoning, China.
FAU - Chen, Duoyun
AU  - Chen D
AD  - Dalian Medical University, Dalian 116044, Liaoning, China.
FAU - Li, Xiaolei
AU  - Li X
AD  - Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to 
      Yangzhou University, Yangzhou, Jiangsu, China.
FAU - Wang, Jingcheng
AU  - Wang J
AD  - Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to 
      Yangzhou University, Yangzhou, Jiangsu, China. Electronic address: 
      jingchengwyz@163.com.
FAU - Sun, Yu
AU  - Sun Y
AD  - Department of Orthopedics, Northern Jiangsu People's Hospital Affiliated to 
      Yangzhou University, Yangzhou, Jiangsu, China. Electronic address: 
      docsunyu@126.com.
LA  - eng
PT  - Journal Article
DEP - 20210105
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Isoflavones)
RN  - 0 (Phenols)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - HOC5567T41 (glabridin)
SB  - IM
MH  - Animals
MH  - Anterior Cruciate Ligament/pathology
MH  - Apoptosis/drug effects
MH  - Autophagy/drug effects
MH  - Cartilage, Articular/pathology
MH  - Catalase/metabolism
MH  - Chondrocytes/*drug effects/metabolism/pathology
MH  - Extracellular Matrix Proteins/genetics
MH  - Humans
MH  - Injections, Intra-Articular
MH  - Isoflavones/administration & dosage/*pharmacology
MH  - Male
MH  - Osteoarthritis, Knee/*drug therapy/etiology/metabolism/pathology
MH  - Oxidative Stress/*drug effects/physiology
MH  - Phenols/administration & dosage/*pharmacology
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Superoxide Dismutase/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Rats
OTO - NOTNLM
OT  - Apoptosis
OT  - Autophagy
OT  - Glabridin
OT  - Osteoarthritis
OT  - Oxidative stress
EDAT- 2021/01/09 06:00
MHDA- 2021/03/06 06:00
CRDT- 2021/01/08 20:12
PHST- 2020/10/13 00:00 [received]
PHST- 2020/12/29 00:00 [revised]
PHST- 2020/12/29 00:00 [accepted]
PHST- 2021/01/09 06:00 [pubmed]
PHST- 2021/03/06 06:00 [medline]
PHST- 2021/01/08 20:12 [entrez]
AID - S0024-3205(20)31752-5 [pii]
AID - 10.1016/j.lfs.2020.118992 [doi]
PST - ppublish
SO  - Life Sci. 2021 Mar 1;268:118992. doi: 10.1016/j.lfs.2020.118992. Epub 2021 Jan 5.