PMID- 36148811
OWN - NLM
STAT- MEDLINE
DCOM- 20221018
LR  - 20221018
IS  - 2042-650X (Electronic)
IS  - 2042-6496 (Linking)
VI  - 13
IP  - 20
DP  - 2022 Oct 17
TI  - Rutin prevents seizures in kainic acid-treated rats: evidence of glutamate 
      levels, inflammation and neuronal loss modulation.
PG  - 10401-10414
LID - 10.1039/d2fo01490d [doi]
AB  - Rutin, a naturally derived flavonoid molecule with known neuroprotective 
      properties, has been demonstrated to have anticonvulsive potential, but the 
      mechanism of this effect is still unclear. The current study aimed to investigate 
      the probable antiseizure mechanisms of rutin in rats using the kainic acid (KA) 
      seizure model. Rutin (50 and 100 mg kg(-1)) and carbamazepine (100 mg kg(-1)) 
      were administered daily by oral gavage for 7 days before KA (15 mg kg(-1)) 
      intraperitoneal (i.p.) injection. Seizure behavior, neuronal cell death, 
      glutamate concentration, excitatory amino acid transporters (EAATs), glutamine 
      synthetase (GS), glutaminase, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic 
      acid (AMPA) receptor subunits GluA1 and GluA2, N-methyl-D-aspartate (NMDA) 
      receptor subunits GluN2A and GluN2B, activated astrocytes, and inflammatory and 
      anti-inflammatory molecules in the hippocampus were evaluated. Supplementation 
      with rutin attenuated seizure severity in KA-treated rats and reversed KA-induced 
      neuronal loss and glutamate elevation in the hippocampus. Decreased glutaminase 
      and GluN2B, and increased EAATs, GS, GluA1, GluA2 and GluN2A were observed with 
      rutin administration. Rutin pretreatment also suppressed activated astrocytes, 
      downregulated the protein levels of inflammatory molecules [interleukin-1beta 
      (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), high mobility 
      group Box 1 (HMGB1), interleukin-1 receptor 1 (IL-1R1), and Toll-like receptor-4 
      (TLR-4)] and upregulated anti-inflammatory molecule interleukin-10 (IL-10) 
      protein expression. Taken together, the results indicate that the preventive 
      treatment of rats with rutin attenuated KA-induced seizures and neuronal loss by 
      decreasing glutamatergic hyperactivity and suppressing the IL-1R1/TLR4-related 
      neuroinflammatory cascade.
FAU - Chang, Anna
AU  - Chang A
AD  - School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan. 
      med0003@mail.fju.edu.tw.
AD  - Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 22060, 
      Taiwan.
FAU - Chang, Yi
AU  - Chang Y
AD  - School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan. 
      med0003@mail.fju.edu.tw.
AD  - Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 22060, 
      Taiwan.
FAU - Wang, Su-Jane
AU  - Wang SJ
AUID- ORCID: 0000-0002-4675-0259
AD  - School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan. 
      med0003@mail.fju.edu.tw.
AD  - Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung 
      University of Science and Technology, Taoyuan 33303, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20221017
PL  - England
TA  - Food Funct
JT  - Food & function
JID - 101549033
RN  - 0 (Amino Acid Transport Systems)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (HMGB1 Protein)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptors, Interleukin-1)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
RN  - 33CM23913M (Carbamazepine)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 5G06TVY3R7 (Rutin)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 77521-29-0 (alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid)
RN  - EC 3.5.1.2 (Glutaminase)
RN  - EC 6.3.1.2 (Glutamate-Ammonia Ligase)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - Amino Acid Transport Systems
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Carbamazepine
MH  - Glutamate-Ammonia Ligase/metabolism/pharmacology
MH  - Glutamic Acid/metabolism
MH  - Glutaminase/genetics/metabolism/pharmacology
MH  - *HMGB1 Protein/genetics/metabolism
MH  - Hippocampus/metabolism
MH  - Inflammation/chemically induced/drug therapy/metabolism
MH  - Interleukin-10/metabolism
MH  - Interleukin-1beta/genetics/metabolism
MH  - Interleukin-6/metabolism
MH  - *Kainic Acid/adverse effects
MH  - N-Methylaspartate/adverse effects/metabolism
MH  - Rats
MH  - Receptors, Interleukin-1/metabolism/therapeutic use
MH  - Rutin/metabolism/pharmacology
MH  - Seizures/chemically induced/drug therapy/metabolism
MH  - Toll-Like Receptor 4/genetics/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/adverse 
      effects/metabolism
EDAT- 2022/09/24 06:00
MHDA- 2022/10/19 06:00
CRDT- 2022/09/23 05:53
PHST- 2022/09/24 06:00 [pubmed]
PHST- 2022/10/19 06:00 [medline]
PHST- 2022/09/23 05:53 [entrez]
AID - 10.1039/d2fo01490d [doi]
PST - epublish
SO  - Food Funct. 2022 Oct 17;13(20):10401-10414. doi: 10.1039/d2fo01490d.