PMID- 35035207
OWN - NLM
STAT- MEDLINE
DCOM- 20220429
LR  - 20220531
IS  - 1090-0535 (Electronic)
IS  - 1090-0535 (Linking)
VI  - 27
DP  - 2021
TI  - Ligustrazine protects against chronic hypertensive glaucoma in rats by inhibiting 
      autophagy via the PI3K-Akt/mTOR pathway.
PG  - 725-733
AB  - PURPOSE: Glaucoma is a leading cause of global irreversible blindness, and 
      characterized by the progressive loss of retinal ganglion cells (RGCs). 
      Ligustrazine (TMP) is a natural product that has shown beneficial effects on 
      various diseases. This study aimed to determine whether ligustrazine produces a 
      therapeutic effect on glaucoma and to investigate its underlying mechanisms. 
      METHODS: A rat chronic hypertensive glaucoma model was induced by episcleral vein 
      cauterization (EVC). Adult Sprague-Dawley (SD) rats were intraperitoneally 
      administered TMP at a dose of 80 mg/kg once a day, from two days before EVC to 
      one month after EVC. To elucidate the role of the mammalian target of rapamycin 
      (mTOR) and phosphoinositide 3-kinase (PI3K), TMP-treated experimental rats were 
      co-treated with the mTOR inhibitor rapamycin (5 mg/kg) or the PI3K inhibitor 
      Ly294002 (10 mg/kg). The intraocular pressure (IOP) of the experimental and 
      control rats was measured every six days. Retinal cells were examined by 
      hematoxylin-eosin and terminal deoxynucleotidyltransferase-mediated biotinylated 
      UTP nick end labeling (TUNEL) staining, as well as transmission electron 
      microscopy. Immunohistochemistry and western blot analysis were performed to 
      measure proteins involved in apoptosis and autophagy. RESULTS: Ligustrazine 
      protected retinal cells from death in experimental glaucoma rats, which was not 
      due to the lowering of IOP, but could be attributable to direct suppression of 
      retinal cell apoptosis. In glaucoma rats, autophagy was markedly activated in 
      retina cells, as evidenced by increased numbers of autophagosomes and the 
      expression of autophagy-related proteins (ATG5 and LC3-II/I). Notably, such 
      alterations in glaucoma rats were almost completely reversed by ligustrazine. The 
      suppressive effects of ligustrazine on apoptosis and autophagy of retina cells 
      were markedly attenuated by the mTOR inhibitor rapamycin or the PI3K inhibitor 
      Ly294002. Additionally, ligustrazine significantly increased the protein levels 
      of phosphorylated PI3K (p-PI3K), protein kinase B (p-Akt), and mTOR (p-mTOR) in 
      glaucoma rats, whereas such increases were attenuated by rapamycin or Ly294002. 
      CONCLUSIONS: These results demonstrate that ligustrazine is protective in 
      experimental glaucoma by inhibiting autophagy via the activation of the 
      PI3K-Akt/mTOR pathway, providing compelling evidence that ligustrazine is 
      potentially therapeutic for patients with glaucoma.
CI  - Copyright (c) 2021 Molecular Vision.
FAU - Du, Hong-Yan
AU  - Du HY
AD  - Department of Ophthalmology, The Affiliated Traditional Chinese Medicine Hospital 
      of Guangzhou Medical University, Guangzhou, China.
FAU - Wang, Rong
AU  - Wang R
AD  - Department of Ophthalmology, The Affiliated Traditional Chinese Medicine Hospital 
      of Guangzhou Medical University, Guangzhou, China.
FAU - Li, Jian-Liang
AU  - Li JL
AD  - Department of Ophthalmology, The Affiliated Traditional Chinese Medicine Hospital 
      of Guangzhou Medical University, Guangzhou, China.
FAU - Luo, Huang
AU  - Luo H
AD  - Department of Ophthalmology, The Affiliated Traditional Chinese Medicine Hospital 
      of Guangzhou Medical University, Guangzhou, China.
FAU - Xie, Xiao-Yan
AU  - Xie XY
AD  - Department of Ophthalmology, The Affiliated Traditional Chinese Medicine Hospital 
      of Guangzhou Medical University, Guangzhou, China.
FAU - Yan, Ran
AU  - Yan R
AD  - Department of Ophthalmology, The Affiliated Traditional Chinese Medicine Hospital 
      of Guangzhou Medical University, Guangzhou, China.
FAU - Jian, Yue-Ling
AU  - Jian YL
AD  - Department of Ophthalmology, The Affiliated Traditional Chinese Medicine Hospital 
      of Guangzhou Medical University, Guangzhou, China.
FAU - Cai, Jin-Ying
AU  - Cai JY
AD  - Department of Ophthalmology, The Affiliated Traditional Chinese Medicine Hospital 
      of Guangzhou Medical University, Guangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211212
PL  - United States
TA  - Mol Vis
JT  - Molecular vision
JID - 9605351
RN  - 0 (Pyrazines)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - V80F4IA5XG (tetramethylpyrazine)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Autophagy
MH  - *Glaucoma/complications/drug therapy/metabolism
MH  - Humans
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - *Proto-Oncogene Proteins c-akt/metabolism
MH  - *Pyrazines/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Retinal Ganglion Cells/metabolism
MH  - Sirolimus/metabolism/pharmacology
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC8711580
EDAT- 2022/01/18 06:00
MHDA- 2022/04/30 06:00
PMCR- 2021/01/01
CRDT- 2022/01/17 05:50
PHST- 2021/03/02 00:00 [received]
PHST- 2021/12/10 00:00 [accepted]
PHST- 2022/01/17 05:50 [entrez]
PHST- 2022/01/18 06:00 [pubmed]
PHST- 2022/04/30 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 61 [pii]
PST - epublish
SO  - Mol Vis. 2021 Dec 12;27:725-733. eCollection 2021.