PMID- 31028292
OWN - NLM
STAT- MEDLINE
DCOM- 20200210
LR  - 20231014
IS  - 1745-7254 (Electronic)
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 40
IP  - 10
DP  - 2019 Oct
TI  - Curculigoside facilitates fear extinction and prevents depression-like behaviors 
      in a mouse learned helplessness model through increasing hippocampal BDNF.
PG  - 1269-1278
LID - 10.1038/s41401-019-0238-4 [doi]
AB  - Curculigoside (CUR) is the main active component of traditional Chinese medicine 
      Curculigoorchioides Gaertn (Xianmao in Chinese), which exhibits a variety of 
      pharmacological activities. In this study we investigated the effects of CUR on 
      fear extinction and related depression-like behaviors in mice. In fear 
      conditioning task, we found that administration of CUR (1.6, 8, 
      40 mg.kg(-1).d(-1), ip, for 7 days) did not affect memory consolidation, but CUR 
      at higher doses (8, 40 mg.kg(-1).d(-1)) significantly facilitated fear 
      extinction, especially on D3 and D4. Moreover, CUR administration significantly 
      ameliorated the fear conditioning-induced depression-like behaviors, likely 
      through promoting fear extinction. We showed that CUR increased the expression of 
      brain-derived neurotrophic factor (BDNF) and phosphorylation of tropomyosin 
      receptor kinase B (TrkB) in the hippocampus, and activated protein kinase B 
      (Akt)-mammalian target of the rapamycin (mTOR) signaling pathway. Administration 
      of the selective TrkB agonist 7,8-dihydroxyflavone (7,8-DHF, 5 mg.kg(-1).d(-1), 
      ip) also facilitated fear extinction, ameliorated depression-like behaviors. We 
      established a mouse learned helplessness (LH) model to evaluate the 
      antidepressant activity of CUR. The spatial memory was assessed in Morris water 
      maze. We showed that LH-induced depression-like behaviors, including prolonged 
      immobility times in forced swim and tail suspension tests as well as spatial 
      memory impairments; LH also downregulated BDNF expression and the Akt-mTOR 
      signaling pathway in the hippocampus. Administration of CUR (1.6, 8, 
      40 mg.kg(-1).d(-1), ip, for 14 days) or 7,8-DHF (5 mg.kg(-1).d(-1), ip, for 3 
      days) prevented LH-induced depression-like behaviors and promoted BDNF expression 
      and the Akt-mTOR signaling pathway. In conclusion, CUR can accelerate the fear 
      memory extinction and ameliorate depression-like behaviors in mice via promoting 
      BDNF expression and activating the Akt-mTOR signaling pathway in the hippocampus.
FAU - Yang, San-Juan
AU  - Yang SJ
AD  - Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of 
      Chinese Medicine, Hefei, 230038, China.
FAU - Song, Zhu-Jin
AU  - Song ZJ
AD  - Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of 
      Chinese Medicine, Hefei, 230038, China.
FAU - Wang, Xun-Cui
AU  - Wang XC
AD  - Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of 
      Chinese Medicine, Hefei, 230038, China.
FAU - Zhang, Zheng-Rong
AU  - Zhang ZR
AD  - Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of 
      Chinese Medicine, Hefei, 230038, China.
FAU - Wu, Sheng-Bing
AU  - Wu SB
AD  - Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of 
      Chinese Medicine, Hefei, 230038, China.
AD  - Anhui Academy of Chinese Medicine, Hefei, 230038, China.
FAU - Zhu, Guo-Qi
AU  - Zhu GQ
AD  - Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of 
      Chinese Medicine, Hefei, 230038, China. guoqizhu@gmail.com.
AD  - Anhui Academy of Chinese Medicine, Hefei, 230038, China. guoqizhu@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20190426
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Bdnf protein, mouse)
RN  - 0 (Benzoates)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glucosides)
RN  - 85643-19-2 (curculigoside)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Benzoates/*pharmacology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Depression/*drug therapy/metabolism
MH  - *Disease Models, Animal
MH  - Glucosides/*pharmacology
MH  - *Helplessness, Learned
MH  - Hippocampus/*drug effects/metabolism
MH  - Male
MH  - Medicine, Chinese Traditional
MH  - Mice
MH  - Mice, Inbred C57BL
PMC - PMC6786307
OTO - NOTNLM
OT  - 8-dihydroxyflavone; fear extinction
OT  - BDNF
OT  - TrkB; Akt-mTOR signaling pathway
OT  - curculigoside; 7
OT  - depression
OT  - hippocampus
OT  - learned helplessness model
COIS- The authors declare no competing interests.
EDAT- 2019/04/28 06:00
MHDA- 2020/02/11 06:00
PMCR- 2020/10/01
CRDT- 2019/04/28 06:00
PHST- 2019/01/09 00:00 [received]
PHST- 2019/04/11 00:00 [accepted]
PHST- 2019/04/28 06:00 [pubmed]
PHST- 2020/02/11 06:00 [medline]
PHST- 2019/04/28 06:00 [entrez]
PHST- 2020/10/01 00:00 [pmc-release]
AID - 10.1038/s41401-019-0238-4 [pii]
AID - 238 [pii]
AID - 10.1038/s41401-019-0238-4 [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2019 Oct;40(10):1269-1278. doi: 10.1038/s41401-019-0238-4. 
      Epub 2019 Apr 26.