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Evaluation of the effect of thymoquinone in d ‐galactose‐induced memory impairments in rats: Role of MAPK , oxidative stress, and neuroinflammation pathways and telomere length
Author(s) -
Oskouei Zahra,
Mehri Soghra,
Kalalinia Fatemeh,
Hosseinzadeh Hossein
Publication year - 2021
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6982
Subject(s) - neuroinflammation , morris water navigation task , oxidative stress , thymoquinone , creb , malondialdehyde , mapk/erk pathway , chemistry , p38 mitogen activated protein kinases , endocrinology , neuroprotection , glial fibrillary acidic protein , pharmacology , medicine , hippocampus , inflammation , antioxidant , biochemistry , signal transduction , gene , immunohistochemistry , transcription factor
D ‐galactose ( d ‐gal) induces aging and memory impairment via oxidative stress and neuroinflammation pathways. This study evaluated the neuroprotective activity of thymoquinone (TQ) against d ‐gal. d ‐gal (400 mg/kg, SC), d ‐gal plus TQ (2.5, 5, 10 mg/kg, i.p.), and TQ alone (2.5 and 10 mg/kg) for 8 weeks were administered to rats. The effect of TQ on learning and memory were studied using the Morris water maze test. Malondialdehyde (MDA) and glutathione (GSH) levels were determined in the hippocampus. The levels of MAPKs (p‐ERK/ERK, p‐P38/P38), cAMP response elements binding (p‐CREB/CREB), advanced glycation end products (AGEs), inflammatory markers (TNFα, IL‐1β), glial fibrillary acidic protein (GFAP), and brain‐derived neurotrophic factor (BDNF) were analyzed by western blotting. Telomere length was evaluated using real‐time PCR. Memory and learning impairment, MDA enhancement, GSH reduction, and neuroinflammation via increasing the TNFα, IL‐1β, and GFAP contents were observed in d ‐gal group. TQ with d ‐gal, improved memory impairment, reduced oxidative stress, and alleviated neuroinflammation. The elevated level of AGEs decreased by TQ compared to d ‐gal. No changes were observed in the levels of p‐ERK/ERK, p‐CREB/CREB, p‐P38/P38, BDNF, and telomere length following administration of d ‐gal or TQ plus d ‐gal. TQ improved memory deficits of d ‐gal through anti‐oxidative and anti‐inflammatory mechanisms.

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