PMID- 36254458
OWN - NLM
STAT- MEDLINE
DCOM- 20221103
LR  - 20230119
IS  - 1948-7193 (Electronic)
IS  - 1948-7193 (Linking)
VI  - 13
IP  - 21
DP  - 2022 Nov 2
TI  - Cyanidin Chloride Improves LPS-Induced Depression-Like Behavior in Mice by 
      Ameliorating Hippocampal Inflammation and Excitotoxicity.
PG  - 3023-3033
LID - 10.1021/acschemneuro.2c00087 [doi]
AB  - Depression is a global disease that places a significant burden on human health. 
      Neuroinflammation and disturbance of glutamate metabolism in brain regions, such 
      as the hippocampus, play vital roles in the development of depression. Previous 
      studies have shown that cyanidin chloride (Cycl) has anti-inflammatory and 
      antioxidant properties with neuroprotective effects in peripheral tissues. 
      However, the effects of Cycl on depression and the possible mechanism by which 
      this compound targets brain regions remain less elucidated. We investigated the 
      role of Cycl in lipopolysaccharide (LPS)-induced depression and examined the 
      influence of the drug on central inflammation and the expression of excitatory 
      amino acid transporters in the hippocampus. We found that prophylactic i.p. 
      application of Cycl at 20 or 40 mg/kg for 5 days significantly reduced the 
      immobility time assessed by the tail suspension test (TST) and forced swim test 
      (FST) in LPS-challenged mice, suggesting an effective antidepressant activity of 
      the drug. Western blotting and immunofluorescence staining in the hippocampus 
      revealed that Cycl inhibited the upregulation of proinflammatory cytokines, 
      including TNF-alpha and IL-6, and suppressed the hyperactivity of microglia induced 
      by LPS, indicating an anti-inflammatory role in the hippocampus. Moreover, 
      treatment with Cycl also recovered the downregulated expression of glial 
      fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF), and 
      glutamate-aspartate transporter (GLAST) and excitatory amino acid transporter 2 
      (EAAT2), two members in the excitatory amino acid transporter family. The role of 
      Cycl was also verified in cultured BV2 and U251 cells. In conclusion, the present 
      in vivo and in vitro studies demonstrate that Cycl exerts potent antidepressant 
      action in an LPS-induced depression model and the underlying mechanism is 
      associated with reduced hippocampal inflammation, improved neurotrophic function, 
      and attenuated excitotoxicity induced by glutamate.
FAU - Qu, Di
AU  - Qu D
AUID- ORCID: 0000-0002-0880-6717
AD  - The College of Life Sciences, Northwest University, Xi'an 710127, Shaanxi 
      Province, China.
AD  - State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, Air Force 
      Medical University, Xi'an 710032, Shaanxi Province, China.
FAU - Ye, Zichen
AU  - Ye Z
AD  - Department of Health Service, Health Service Training Base, Air Force Medical 
      University, Xi'an 710032, Shaanxi Province, China.
FAU - Zhang, Wenli
AU  - Zhang W
AD  - The College of Life Sciences, Northwest University, Xi'an 710127, Shaanxi 
      Province, China.
AD  - State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, Air Force 
      Medical University, Xi'an 710032, Shaanxi Province, China.
FAU - Dai, Bing
AU  - Dai B
AD  - The College of Life Sciences, Northwest University, Xi'an 710127, Shaanxi 
      Province, China.
AD  - State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, Air Force 
      Medical University, Xi'an 710032, Shaanxi Province, China.
FAU - Chen, Guo
AU  - Chen G
AD  - State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, Air Force 
      Medical University, Xi'an 710032, Shaanxi Province, China.
FAU - Wang, Li
AU  - Wang L
AD  - State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, Air Force 
      Medical University, Xi'an 710032, Shaanxi Province, China.
FAU - Shao, Xiaolong
AU  - Shao X
AD  - State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, Air Force 
      Medical University, Xi'an 710032, Shaanxi Province, China.
FAU - Xiang, An
AU  - Xiang A
AD  - State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, Air Force 
      Medical University, Xi'an 710032, Shaanxi Province, China.
FAU - Lu, Zifan
AU  - Lu Z
AUID- ORCID: 0000-0001-5390-5020
AD  - State Key Laboratory of Cancer Biology, Department of Biopharmaceutics, Air Force 
      Medical University, Xi'an 710032, Shaanxi Province, China.
FAU - Shi, Juan
AU  - Shi J
AD  - Department of Human Anatomy, Histology and Embryology & K. K. Leung Brain 
      Research Centre, Preclinical School of Medicine, Air Force Medical University, 
      Xi'an 710032, Shaanxi Province, China.
LA  - eng
PT  - Journal Article
DEP - 20221017
PL  - United States
TA  - ACS Chem Neurosci
JT  - ACS chemical neuroscience
JID - 101525337
RN  - 0 (Lipopolysaccharides)
RN  - 7732ZHU564 (cyanidin)
RN  - 0 (Antidepressive Agents)
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Humans
MH  - *Lipopolysaccharides/pharmacology
MH  - *Depression/drug therapy
MH  - Antidepressive Agents/pharmacology
MH  - Hippocampus/metabolism
MH  - Inflammation/metabolism
MH  - Glutamic Acid/metabolism
OTO - NOTNLM
OT  - BDNF
OT  - EAAT
OT  - cyanidin chloride
OT  - depression
OT  - hippocampus
OT  - neuroinflammation
EDAT- 2022/10/19 06:00
MHDA- 2022/11/04 06:00
CRDT- 2022/10/18 03:02
PHST- 2022/10/19 06:00 [pubmed]
PHST- 2022/11/04 06:00 [medline]
PHST- 2022/10/18 03:02 [entrez]
AID - 10.1021/acschemneuro.2c00087 [doi]
PST - ppublish
SO  - ACS Chem Neurosci. 2022 Nov 2;13(21):3023-3033. doi: 
      10.1021/acschemneuro.2c00087. Epub 2022 Oct 17.