PMID- 32685478
OWN - NLM
STAT- MEDLINE
DCOM- 20210416
LR  - 20210416
IS  - 2314-6141 (Electronic)
IS  - 2314-6133 (Print)
VI  - 2020
DP  - 2020
TI  - Beneficial Effects of Crocin against Depression via Pituitary Adenylate 
      Cyclase-Activating Polypeptide.
PG  - 3903125
LID - 10.1155/2020/3903125 [doi]
LID - 3903125
AB  - Depression is one of the foremost psychological illness, and the exact mechanism 
      is unclear. Recent studies have reported that the pituitary adenylate 
      cyclase-activating polypeptide (PACAP) signaling pathway is involved in the 
      progression of depression. In the present study, we extracted crocin from the 
      traditional Chinese medicine (TCM), Gardenia jasminoides Ellis, to evaluate its 
      antidepressant effect and clarify the underlying mechanism. Here, we established 
      a chronic unpredictable mild stress (CUMS) mouse model to assess whether crocin 
      can improve depression-like behavior in an open field test (OFT), tail suspension 
      test (TST), forced swimming test (FST), and sucrose preference test (SPT). A 
      corticosterone (CORT) model of PC12 was set up to explore the antidepressant 
      mechanism of crocin. We pretreated PC12 cells with crocin for 1 hour and then 
      stimulated the cells with CORT for 24 hours. Cell survival was detected by 
      Hoechst staining and MTT assay. The expression of PACAP, cyclic adenosine 
      monophosphate (cAMP) response element binding protein (CREB), and extracellular 
      regulated protein kinases (ERK) were analyzed by western blotting. PACAP RNAi was 
      used to interfere with PC12 cells to downregulate the content of PACAP. The 
      results showed that crocin (30 mg/kg) significantly reversed the decrease of body 
      weight and elevation of serum CORT, mitigated CUMS induced depression-like 
      behaviors of mice, and crocin (12.5 mumol/L) protected PC12 cells against CORT 
      (200 mumol/L)-induced injury. Furthermore, crocin greatly increased the protein 
      expression of PACAP and phosphorylation of ERK and CREB in the CORT model. PACAP 
      RNAi cancelled the neuroprotective effect of crocin. In conclusion, these results 
      indicated that crocin exerted an antidepressant effect via upregulating PACAP and 
      its downstream ERK and CREB signaling pathways.
CI  - Copyright (c) 2020 Linyu Lu et al.
FAU - Lu, Linyu
AU  - Lu L
AUID- ORCID: 0000-0003-0520-8444
AD  - School of Medicine and Holistic Integrative Medicine, Nanjing University of 
      Chinese Medicine, Nanjing 210023, China.
FAU - Wu, Die
AU  - Wu D
AUID- ORCID: 0000-0002-8536-8095
AD  - School of Medicine and Holistic Integrative Medicine, Nanjing University of 
      Chinese Medicine, Nanjing 210023, China.
FAU - Wang, Kai
AU  - Wang K
AUID- ORCID: 0000-0001-7204-4422
AD  - School of Medicine and Holistic Integrative Medicine, Nanjing University of 
      Chinese Medicine, Nanjing 210023, China.
FAU - Tang, Juanjuan
AU  - Tang J
AUID- ORCID: 0000-0002-1397-8687
AD  - School of Medicine and Holistic Integrative Medicine, Nanjing University of 
      Chinese Medicine, Nanjing 210023, China.
FAU - Chen, Gang
AU  - Chen G
AUID- ORCID: 0000-0002-3507-1218
AD  - Interdisciplinary Institute for Personalized Medicine in Brain Disorders, and 
      Research Center for Formula and Syndromes, Jinan University, Guangzhou 510632, 
      China.
AD  - Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu 
      226001, China.
LA  - eng
PT  - Journal Article
DEP - 20200624
PL  - United States
TA  - Biomed Res Int
JT  - BioMed research international
JID - 101600173
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Pituitary Adenylate Cyclase-Activating Polypeptide)
RN  - 36-88-4 (Carotenoids)
RN  - 877GWI46C2 (crocin)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Body Weight/drug effects
MH  - Carotenoids/chemistry/*therapeutic use
MH  - Chronic Disease
MH  - Corticosterone/blood
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Depression/*drug therapy/*metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Male
MH  - Mice, Inbred BALB C
MH  - Models, Biological
MH  - Neuroprotective Agents/metabolism
MH  - PC12 Cells
MH  - Phosphorylation/drug effects
MH  - Pituitary Adenylate Cyclase-Activating Polypeptide/*metabolism
MH  - Rats
MH  - Stress, Psychological/complications
PMC - PMC7334775
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2020/07/21 06:00
MHDA- 2021/04/17 06:00
PMCR- 2020/06/24
CRDT- 2020/07/21 06:00
PHST- 2020/03/04 00:00 [received]
PHST- 2020/05/17 00:00 [revised]
PHST- 2020/05/26 00:00 [accepted]
PHST- 2020/07/21 06:00 [entrez]
PHST- 2020/07/21 06:00 [pubmed]
PHST- 2021/04/17 06:00 [medline]
PHST- 2020/06/24 00:00 [pmc-release]
AID - 10.1155/2020/3903125 [doi]
PST - epublish
SO  - Biomed Res Int. 2020 Jun 24;2020:3903125. doi: 10.1155/2020/3903125. eCollection 
      2020.