PMID- 30745820
OWN - NLM
STAT- MEDLINE
DCOM- 20200113
LR  - 20211204
IS  - 1449-2288 (Electronic)
IS  - 1449-2288 (Linking)
VI  - 15
IP  - 2
DP  - 2019
TI  - Icariin Inhibits Endoplasmic Reticulum Stress-induced Neuronal Apoptosis after 
      Spinal Cord Injury through Modulating the PI3K/AKT Signaling Pathway.
PG  - 277-286
LID - 10.7150/ijbs.30348 [doi]
AB  - Endoplasmic reticulum (ER) stress-induced neuronal apoptosis is a crucial 
      pathological process of spinal cord injury (SCI). In our previous study, icariin 
      (ICA) showed neuroprotective effects in SCI. However, the relationships between 
      ER stress and ICA in SCI are unclear yet. Therefore, whether ICA could ameliorate 
      SCI via attenuating ER stress was investigated in vitro and in vivo. Adult mice 
      were established SCI model and received vehicle solution or ICA by gavage once 
      per day in vivo. The primary cultured cells were treated with or without 
      thapsigargin (TG), ICA or LY294002 to induce ER stress in vitro. Motor 
      dysfunction, neuronal apoptosis, tissue damage and inhibition of PI3K/AKT pathway 
      were induced by ER stress after SCI. But ICA administration significantly 
      enhanced motor recovery and protected spinal cord tissues against infraction and 
      hemorrhage, etc. post injury. Meanwhile, the expression of ER stress markers 
      ATF6, IRE1alpha, GRP78, XBP1 and eIF2alpha was decreased, while the level of p-AKT/AKT 
      was increased by ICA. Furthermore, ICA significantly inhibited the expression of 
      ER stress apoptotic proteins caspase-12, CHOP, Bax/Bcl-2, caspase-9 and 
      caspase-3. Moreover, immunofluorescence double staining indicated that ICA 
      reduced GRP78, CHOP and TUNEL positive neurons following SCI. However, this 
      beneficial effect of ICA was abolished by PI3K/AKT inhibitor LY294002 in vitro. 
      Finally, ICA preserved the ultra-structure of ER by transmission electron 
      microscope histologically. This study suggested that the neuroprotective effect 
      of ICA on motor recovery and neuronal survival was related to attenuating ER 
      stress via PI3K/AKT signaling pathway after SCI.
FAU - Li, Haotian
AU  - Li H
AD  - Department of Spine Surgery, Tongji Hospital, Tongji University School of 
      Medicine, Shanghai 200065, China.
AD  - Key Laboratory of spine and spinal cord injury repair and regeneration (Tongji 
      University), Ministry of Education, Shanghai, China.
FAU - Zhang, Xinran
AU  - Zhang X
AD  - School & Hospital of Stomatology, Tongji University, Shanghai Engineering 
      Research Center of Tooth Restoration and Regeneration, Shanghai 200072, China.
FAU - Qi, Xi
AU  - Qi X
AD  - Department of Spine Surgery, Tongji Hospital, Tongji University School of 
      Medicine, Shanghai 200065, China.
AD  - Key Laboratory of spine and spinal cord injury repair and regeneration (Tongji 
      University), Ministry of Education, Shanghai, China.
FAU - Zhu, Xu
AU  - Zhu X
AD  - Department of Spine Surgery, Tongji Hospital, Tongji University School of 
      Medicine, Shanghai 200065, China.
AD  - Key Laboratory of spine and spinal cord injury repair and regeneration (Tongji 
      University), Ministry of Education, Shanghai, China.
FAU - Cheng, Liming
AU  - Cheng L
AD  - Department of Spine Surgery, Tongji Hospital, Tongji University School of 
      Medicine, Shanghai 200065, China.
AD  - Key Laboratory of spine and spinal cord injury repair and regeneration (Tongji 
      University), Ministry of Education, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190101
PL  - Australia
TA  - Int J Biol Sci
JT  - International journal of biological sciences
JID - 101235568
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (Flavonoids)
RN  - 0 (Hspa5 protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - VNM47R2QSQ (icariin)
SB  - IM
MH  - Animals
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Endoplasmic Reticulum Stress/*drug effects/physiology
MH  - Flavonoids/*therapeutic use
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microscopy, Electron, Transmission
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Signal Transduction/drug effects
MH  - Spinal Cord Injuries/*drug therapy/*metabolism
PMC - PMC6367543
OTO - NOTNLM
OT  - PI3K/AKT
OT  - endoplasmic reticulum stress
OT  - icariin
OT  - neuroprotection
OT  - spinal cord injury
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2019/02/13 06:00
MHDA- 2020/01/14 06:00
PMCR- 2019/01/01
CRDT- 2019/02/13 06:00
PHST- 2018/10/01 00:00 [received]
PHST- 2018/11/28 00:00 [accepted]
PHST- 2019/02/13 06:00 [entrez]
PHST- 2019/02/13 06:00 [pubmed]
PHST- 2020/01/14 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - ijbsv15p0277 [pii]
AID - 10.7150/ijbs.30348 [doi]
PST - epublish
SO  - Int J Biol Sci. 2019 Jan 1;15(2):277-286. doi: 10.7150/ijbs.30348. eCollection 
      2019.