Involvement of estrogen receptor activation in kaempferol-3-O-glucoside's protection against aging-related cognition impairment and microglial inflammation.
Exp Cell Res
; 433(2): 113849, 2023 12 15.
Article
in En
| MEDLINE
| ID: mdl-37926343
ABSTRACT
Estrogens have been demonstrated to inhibit age-related cognitive decline via binding to estrogen receptors (ERs). As a natural flavonoid component of Cuscuta Chinensis Lam., Kaempferol-3-O-glucoside (K-3-G) not only possesses anti-neuroinflammatory potential but also functions as an agonist for ERα and ERß. This study aimed to determine whether K-3-G improved cognition during the aging process, with an emphasis on its effect on microglial inflammation. In vivo, K-3-G (5 or 10 mg/kg/day) was orally given to the senescence-accelerated mouse prone 8 (SAMP8) mice from six to eight-month old. In addition to mitigating the memory and learning deficits of SAMP8 mice, K-3-G upregulated the expression of ERα and ERß in their hippocampal CA1 region, with the higher dose being more effective. Less Iba-1+ microglial cells presented in SAMP8 mice treated with K-3-G. The formation of NLR Family Pyrin Domain Containing 3 (NLRP3) complex, production of pro-inflammatory cytokines and oxidative stress-related markers, as well as expression of pro-apoptotic proteins were reduced by K-3-G. In vitro, BV2 microglial cells exposed to oligomeric amyloid beta (Aß)1-42 were treated with 100 µM K-3-G. K-3-G showed similar anti-inflammatory effects on BV2 cells as in vivo. K-3-G-induced alterations were partly diminished by fulvestrant, an ER antagonist. Moreover, dual-luciferase reporter system demonstrated that K-3-G induced ER expression by activating the transcription of estrogen-response elements (EREs). Collectively, these findings demonstrate that K-3-G may be a novel therapeutic agent for senescence-related cognitive impairment by inhibiting microglial inflammation through its action on ERs.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aging
/
Receptors, Estrogen
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Anti-Inflammatory Agents, Non-Steroidal
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Kaempferols
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Estrogen Receptor alpha
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Estrogen Receptor beta
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Cognitive Dysfunction
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Monosaccharides
Limits:
Animals
Language:
En
Journal:
Exp Cell Res
Year:
2023
Document type:
Article