PMID- 31190087
OWN - NLM
STAT- MEDLINE
DCOM- 20200831
LR  - 20200831
IS  - 1432-1912 (Electronic)
IS  - 0028-1298 (Linking)
VI  - 392
IP  - 10
DP  - 2019 Oct
TI  - Neuroprotective effect of chlorogenic acid in global cerebral 
      ischemia-reperfusion rat model.
PG  - 1293-1309
LID - 10.1007/s00210-019-01670-x [doi]
AB  - The ischemic cascade is initiated in the hypoperfused region of the brain that 
      leads to neuronal cell death. Identification of multi-target inhibitor against 
      prominent molecular mediators of ischemic cascade might be a suitable strategy to 
      combat cerebral ischemic stroke. The present study is designed to evaluate the 
      neuroprotective efficacy of chlorogenic acid (CGA) in the global cerebral 
      ischemic rat model. The effective dose of CGA was evaluated on the basis of 
      reduction in cerebral infarction area percentage, Evans blue extravasation, and 
      restoration of brain water content. The expression of tumor necrosis factor-alpha 
      (TNF-alpha), inducible nitric oxide synthase (iNOS), and caspase-3 was evaluated by 
      immunohistochemistry and morphological and cellular alterations in the cortex 
      were observed by brain histology. The level of glutamate, calcium, and nitrate in 
      different regions of the brain, as well as cerebrospinal fluid (CSF), was 
      evaluated. The level of calcium and nitrate was compared with ifenprodil-an 
      antagonist of N-methyl-D-aspartate receptor (NMDAR) and 7-nitroindazole-an 
      inhibitor of neuronal nitric oxide synthase (nNOS) respectively. Further, 
      molecular docking was performed to compare the inhibition potential of CGA 
      against NMDAR and nNOS with their inhibitors. Dose optimization results revealed 
      that intranasal administration of CGA (10 mg/kg b.w.) significantly reduced the 
      cerebral infarction area, Evans blue extravasation and restored the brain water 
      content compared with ischemia group. It also significantly reduced the calcium, 
      nitrate, and glutamate levels compared with ischemia group in the cortex, 
      hippocampus cerebellum, and CSF. Immunohistochemical analysis revealed that CGA 
      significantly reduced the expression of TNF-alpha, iNOS, and caspase-3 as compared 
      with the ischemia group. In molecular docking study, CGA displayed similar 
      binding interaction as that of Ifenprodil and 7-nitroindazole with NMDAR and nNOS 
      respectively. The current findings suggest that the treatment with CGA confers 
      neuroprotection in global ischemic insult by inhibiting and downregulating the 
      different molecular markers of cerebral ischemia.
FAU - Kumar, Gaurav
AU  - Kumar G
AD  - Electrophysiology Lab, School of Biomedical Engineering, Indian Institute of 
      Technology (Banaras Hindu University), Varanasi, India.
FAU - Mukherjee, Sumedha
AU  - Mukherjee S
AD  - Electrophysiology Lab, School of Biomedical Engineering, Indian Institute of 
      Technology (Banaras Hindu University), Varanasi, India.
FAU - Paliwal, Pankaj
AU  - Paliwal P
AD  - Department of Pharmaceutical Engineering and Technology, Indian Institute of 
      Technology (Banaras Hindu University), Varanasi, India.
FAU - Singh, Saumitra Sen
AU  - Singh SS
AD  - Department of Biochemistry, Institute of Science, Banaras Hindu University, 
      Varanasi, India.
FAU - Birla, Hareram
AU  - Birla H
AD  - Department of Biochemistry, Institute of Science, Banaras Hindu University, 
      Varanasi, India.
FAU - Singh, Surya Pratap
AU  - Singh SP
AD  - Department of Biochemistry, Institute of Science, Banaras Hindu University, 
      Varanasi, India.
FAU - Krishnamurthy, Sairam
AU  - Krishnamurthy S
AD  - Department of Pharmaceutical Engineering and Technology, Indian Institute of 
      Technology (Banaras Hindu University), Varanasi, India.
FAU - Patnaik, Ranjana
AU  - Patnaik R
AUID- ORCID: 0000-0002-8131-177X
AD  - Electrophysiology Lab, School of Biomedical Engineering, Indian Institute of 
      Technology (Banaras Hindu University), Varanasi, India. 
      rpatnaik.bme@iitbhu.ac.in.
LA  - eng
PT  - Journal Article
DEP - 20190612
PL  - Germany
TA  - Naunyn Schmiedebergs Arch Pharmacol
JT  - Naunyn-Schmiedeberg's archives of pharmacology
JID - 0326264
RN  - 0 (Neuroprotective Agents)
RN  - 318ADP12RI (Chlorogenic Acid)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos1 protein, rat)
RN  - EC 1.14.13.39 (Nos2 protein, rat)
SB  - IM
MH  - Animals
MH  - Brain Ischemia/pathology/*prevention & control
MH  - Cerebral Infarction/drug therapy/pathology
MH  - Chlorogenic Acid/administration & dosage/*pharmacology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Male
MH  - Molecular Docking Simulation
MH  - Neuroprotective Agents/administration & dosage/*pharmacology
MH  - Nitric Oxide Synthase Type I/metabolism
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Stroke/pathology/*prevention & control
OTO - NOTNLM
OT  - Chlorogenic acid
OT  - Immunohistochemistry
OT  - Intranasal
OT  - Ischemic stroke
OT  - Molecular docking
OT  - Neuroprotection
EDAT- 2019/06/14 06:00
MHDA- 2020/09/01 06:00
CRDT- 2019/06/14 06:00
PHST- 2019/01/06 00:00 [received]
PHST- 2019/05/22 00:00 [accepted]
PHST- 2019/06/14 06:00 [pubmed]
PHST- 2020/09/01 06:00 [medline]
PHST- 2019/06/14 06:00 [entrez]
AID - 10.1007/s00210-019-01670-x [pii]
AID - 10.1007/s00210-019-01670-x [doi]
PST - ppublish
SO  - Naunyn Schmiedebergs Arch Pharmacol. 2019 Oct;392(10):1293-1309. doi: 
      10.1007/s00210-019-01670-x. Epub 2019 Jun 12.