PMID- 31322238
OWN - NLM
STAT- MEDLINE
DCOM- 20200113
LR  - 20211204
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 20
IP  - 3
DP  - 2019 Sep
TI  - The antidepressant effects of apigenin are associated with the promotion of 
      autophagy via the mTOR/AMPK/ULK1 pathway.
PG  - 2867-2874
LID - 10.3892/mmr.2019.10491 [doi]
AB  - The present study aimed to investigate whether apigenin elicits antidepressant 
      effects in depressant‑like mice via the regulation of autophagy. The 
      depressant‑like behaviors were established in a chronic restraint stress model. 
      Male BALB/c mice were subjected to restraint stress for 6 h/day for a period of 
      21 days, and deficits in sucrose preference, tail suspension and forced swim 
      tests were confirmed to be improved following oral apigenin. To investigate the 
      underlining mechanisms, the hippocampal levels of p62 and microtubule‑associated 
      protein light chain 3‑II/I (LC3‑II/I) were measured using western blot analysis. 
      The expression levels of LC3‑II/I and p62 indicated that the significantly 
      inhibited autophagy level induced by chronic restraint stress can be increased 
      following apigenin treatment. Similar to the level of autophagy, the expression 
      levels of adenosine monophosphate‑activated protein kinase (AMPK) and Unc‑51 like 
      autophagy activating kinase‑1 were downregulated after chronic restraint stress 
      stimulation and, subsequently upregulated following treatment with apigenin. 
      Conversely, the levels of mammalian target of rapamycin (mTOR) were increased in 
      chronic restraint stress mice and inhibited by apigenin. Collectively, the 
      present findings indicated that apigenin potentially promotes autophagy via the 
      AMPK/mTOR pathway and induces antidepressive effects in chronic restraint stress 
      mice.
FAU - Zhang, Xiaolong
AU  - Zhang X
AD  - College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 
      210023, P.R. China.
FAU - Bu, Hongmin
AU  - Bu H
AD  - Lianyungang Food and Drug Inspection Center, Lianyungang, Jiangsu 222000, P.R. 
      China.
FAU - Jiang, Yan
AU  - Jiang Y
AD  - Lianyungang Food and Drug Inspection Center, Lianyungang, Jiangsu 222000, P.R. 
      China.
FAU - Sun, Guangda
AU  - Sun G
AD  - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources 
      Industrialization, Nanjing, Jiangsu 210023, P.R. China.
FAU - Jiang, Ruizhi
AU  - Jiang R
AD  - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources 
      Industrialization, Nanjing, Jiangsu 210023, P.R. China.
FAU - Huang, Xiaoyan
AU  - Huang X
AD  - Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources 
      Industrialization, Nanjing, Jiangsu 210023, P.R. China.
FAU - Duan, Huifang
AU  - Duan H
AD  - College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 
      210023, P.R. China.
FAU - Huang, Zhiheng
AU  - Huang Z
AD  - College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 
      210023, P.R. China.
FAU - Wu, Qinan
AU  - Wu Q
AD  - College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 
      210023, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20190712
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Antidepressive Agents)
RN  - 7V515PI7F6 (Apigenin)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Autophagy-Related Protein-1 Homolog)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Ulk1 protein, mouse)
RN  - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinase Kinases
MH  - Animals
MH  - Antidepressive Agents/pharmacology/*therapeutic use
MH  - Apigenin/pharmacology/*therapeutic use
MH  - Autophagy/*drug effects
MH  - Autophagy-Related Protein-1 Homolog/metabolism
MH  - Depression/*drug therapy/metabolism
MH  - Male
MH  - Mice, Inbred BALB C
MH  - Protein Kinases/metabolism
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
EDAT- 2019/07/20 06:00
MHDA- 2020/01/14 06:00
CRDT- 2019/07/20 06:00
PHST- 2019/01/06 00:00 [received]
PHST- 2019/06/06 00:00 [accepted]
PHST- 2019/07/20 06:00 [pubmed]
PHST- 2020/01/14 06:00 [medline]
PHST- 2019/07/20 06:00 [entrez]
AID - 10.3892/mmr.2019.10491 [doi]
PST - ppublish
SO  - Mol Med Rep. 2019 Sep;20(3):2867-2874. doi: 10.3892/mmr.2019.10491. Epub 2019 Jul 
      12.