PMID- 29405769
OWN - NLM
STAT- MEDLINE
DCOM- 20190107
LR  - 20190107
IS  - 1477-0903 (Electronic)
IS  - 0960-3271 (Linking)
VI  - 37
IP  - 10
DP  - 2018 Oct
TI  - Thymoquinone alleviates the experimentally induced Alzheimer's disease 
      inflammation by modulation of TLRs signaling.
PG  - 1092-1104
LID - 10.1177/0960327118755256 [doi]
AB  - Alzheimer's disease (AD) is characterized by a robust inflammatory response 
      elicited by the accumulation and deposition of amyloid-beta (Abeta) within the brain. 
      Abeta induces detrimental inflammatory responses through toll-like receptors (TLRs) 
      signaling pathway. Thymoquinone (TQ), the main active constituent of Nigella 
      sativa oil, has been reported by several previous studies for its potent 
      anti-inflammatory effect. The aim of this study is to elucidate the effect of TQ 
      in improving learning and memory, using a rat model of AD induced by a 
      combination of aluminum chloride (AlCl(3)) and d-galactose (d-Gal). TQ was 
      administered orally at doses of 10, 20, and 40 mg/kg/day for 14 days after AD 
      induction. Memory functions were assessed using the step through passive 
      avoidance test. Amyloid plaques were shown to be present using hematoxylin and 
      eosin staining. Tumor necrosis factor-alpha (TNF-alpha) and Interleukin-1beta (IL-1beta) 
      levels in brain were assessed via ELISA and profiling TLR-2, TLR-4, myeloid 
      differential factor 88, toll-interleukin-1 receptor domain-containing 
      adapter-inducing interferon-beta, interferon regulatory factor 3 (IRF-3), and 
      nuclear factor-kappaB (NF-kappaB) expressions via real-time polymerase chain reaction. TQ 
      improved AD rat cognitive decline, decreased Abeta formation and accumulation, 
      significantly decreased TNF-alpha and IL-1beta at all levels of doses and significantly 
      downregulated the expression of TLRs pathway components as well as their 
      downstream effectors NF-kappaB and IRF-3 mRNAs at all levels of doses ( p < 0.05). We 
      concluded that TQ reduced the inflammation induced by d-Gal/AlCl(3) combination. 
      It is therefore reasonable to assign the anti-inflammatory responses to the 
      modulation of TLRs pathway.
FAU - Abulfadl, Y S
AU  - Abulfadl YS
AD  - 1 Department of Pharmacology, Toxicology, and Biochemistry, Faculty of 
      Pharmaceutical Sciences and Pharmaceutical Industries, Future University, Cairo, 
      Egypt.
FAU - El-Maraghy, N N
AU  - El-Maraghy NN
AD  - 1 Department of Pharmacology, Toxicology, and Biochemistry, Faculty of 
      Pharmaceutical Sciences and Pharmaceutical Industries, Future University, Cairo, 
      Egypt.
FAU - Ahmed, Aa Eissa
AU  - Ahmed AE
AD  - 2 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan 
      University, Helwan, Egypt.
FAU - Nofal, S
AU  - Nofal S
AD  - 2 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan 
      University, Helwan, Egypt.
FAU - Abdel-Mottaleb, Y
AU  - Abdel-Mottaleb Y
AD  - 1 Department of Pharmacology, Toxicology, and Biochemistry, Faculty of 
      Pharmaceutical Sciences and Pharmaceutical Industries, Future University, Cairo, 
      Egypt.
FAU - Badary, O A
AU  - Badary OA
AD  - 3 Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, 
      Cairo, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20180206
PL  - England
TA  - Hum Exp Toxicol
JT  - Human & experimental toxicology
JID - 9004560
RN  - 0 (Benzoquinones)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Tlr2 protein, rat)
RN  - 0 (Tlr4 protein, rat)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 3CYT62D3GA (Aluminum Chloride)
RN  - O60IE26NUF (thymoquinone)
RN  - X2RN3Q8DNE (Galactose)
SB  - IM
MH  - Aluminum Chloride/toxicity
MH  - Alzheimer Disease/metabolism/pathology/*prevention & control
MH  - Animals
MH  - Benzoquinones/*pharmacology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Galactose/toxicity
MH  - Gene Expression Profiling
MH  - Inflammation/chemically induced/metabolism/*prevention & control
MH  - Interleukin-1beta/metabolism
MH  - Learning
MH  - Male
MH  - Memory
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Real-Time Polymerase Chain Reaction
MH  - Signal Transduction/*drug effects
MH  - Toll-Like Receptor 2/genetics/*metabolism
MH  - Toll-Like Receptor 4/genetics/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - IL-1beta
OT  - TLR-2
OT  - TLR-4
OT  - TNF-alpha
OT  - thymoquinone
EDAT- 2018/02/07 06:00
MHDA- 2019/01/08 06:00
CRDT- 2018/02/07 06:00
PHST- 2018/02/07 06:00 [pubmed]
PHST- 2019/01/08 06:00 [medline]
PHST- 2018/02/07 06:00 [entrez]
AID - 10.1177/0960327118755256 [doi]
PST - ppublish
SO  - Hum Exp Toxicol. 2018 Oct;37(10):1092-1104. doi: 10.1177/0960327118755256. Epub 
      2018 Feb 6.