PMID- 36865741
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230304
IS  - 1741-427X (Print)
IS  - 1741-4288 (Electronic)
IS  - 1741-427X (Linking)
VI  - 2023
DP  - 2023
TI  - Naringin Prevents Cognitive Dysfunction in Aging Rats by Inhibiting Toll-Like 
      Receptor 4 (TLR4)/NF-kappaB Pathway and Endoplasmic Reticulum Stress.
PG  - 2919811
LID - 10.1155/2023/2919811 [doi]
LID - 2919811
AB  - OBJECTIVE: Naringin is a flavonoid derived from Chinese herbs. According to 
      earlier studies, naringin may have the potential to alleviate aging-induced 
      cognitive dysfunction. Therefore, this study attempted to explore the protective 
      effect and underlying mechanism of naringin on aging rats with cognitive 
      dysfunction. METHODS: After the construction of a model of aging rats with 
      cognitive dysfunction through subcutaneous injection of D-galactose (D-gal; 
      150 mg/kg), intragastric administration of naringin (100 mg/kg) was performed for 
      treatment. Behavioral tests, including Morris water maze test (MWM), novel object 
      recognition test (NORT), and fear conditioning test, were used to measure the 
      cognitive function; ELISA and biochemical tests were used to determine the levels 
      of interleukin (IL)-1beta, IL-6, monocyte chemoattractant protein-1 (MCP-1), 
      brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), 
      malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in the hippocampus of 
      rats in each group, respectively; H&E staining was used to observe the 
      pathological changes in the hippocampus; Western blot was used to examine the 
      expression of toll-like receptor 4 (TLR4)/NF-kappaB pathway-related proteins and 
      endoplasmic reticulum (ER) stress-related proteins in the hippocampus. RESULTS: 
      The model was successfully constructed by subcutaneous injection of D-gal 
      (150 mg/kg). The behavioral test results showed that naringin could ameliorate 
      the cognitive dysfunction and alleviate the histopathological damage of 
      hippocampus. Moreover, naringin significantly improve the inflammatory response 
      (the levels of IL-1beta, IL-6, and MCP-1 were decreased), oxidative stress response 
      (MDA level was increased while GSH-Px activity was decreased), and ER stress (the 
      expression of glucose-regulated protein 78 (GRP78), C/-EBP homologous protein 
      (CHOP), and transcription factor 6 (ATF6) expression was downregulated), and 
      increased the levels of neurotrophic factors BDNF and NGF in D-gal rats. Besides, 
      further mechanistic studies revealed the downregulation of naringin on TLR4/NF-kappaB 
      pathway activity. CONCLUSION: Naringin may inhibit inflammatory response, 
      oxidative stress, and ER stress by downregulating TLR4/NF-kappaB pathway activity, 
      thereby improving cognitive dysfunction and alleviating histopathological damage 
      of hippocampus in aging rats. Briefly, naringin is an effective drug for the 
      treatment of cognitive dysfunction.
CI  - Copyright (c) 2023 Xiao-jie Dai et al.
FAU - Dai, Xiao-Jie
AU  - Dai XJ
AD  - Internal Medicine-Neurology, Xi'an Gaoxin Hospital, Shaanxi 710075, China.
FAU - Jia, Yi
AU  - Jia Y
AD  - Internal Medicine-Neurology, Xi'an Gaoxin Hospital, Shaanxi 710075, China.
FAU - Cao, Rui
AU  - Cao R
AD  - Internal Medicine-Neurology, Qingyang People's Hospital, Qingyang, Gansu 745000, 
      China.
FAU - Zhou, Mei-Ning
AU  - Zhou MN
AUID- ORCID: 0000-0003-1702-313X
AD  - The Third Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710068, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20230221
PL  - United States
TA  - Evid Based Complement Alternat Med
JT  - Evidence-based complementary and alternative medicine : eCAM
JID - 101215021
PMC - PMC9974290
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2023/03/04 06:00
MHDA- 2023/03/04 06:01
PMCR- 2023/02/21
CRDT- 2023/03/03 02:35
PHST- 2022/07/29 00:00 [received]
PHST- 2022/08/23 00:00 [revised]
PHST- 2022/09/23 00:00 [accepted]
PHST- 2023/03/03 02:35 [entrez]
PHST- 2023/03/04 06:00 [pubmed]
PHST- 2023/03/04 06:01 [medline]
PHST- 2023/02/21 00:00 [pmc-release]
AID - 10.1155/2023/2919811 [doi]
PST - epublish
SO  - Evid Based Complement Alternat Med. 2023 Feb 21;2023:2919811. doi: 
      10.1155/2023/2919811. eCollection 2023.