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- W4386204120 abstract "Abstract Prenylated flavonoids are promising nutraceuticals with diverse bioactivities. However, publications on the mechanism of action and structure–activity relationship of prenylated flavonoids are limited. In the present work, six novel prenylated flavonoids (C8–C13) with diversity structure were prepared. Their estrogen receptor (ER) modulator activity and neuroprotective activity were investigated by cell assays. C8, C9, and C10 with 8‐C‐prenyl and 7‐OH showed agonistic activities toward ERα and ERβ, along with high ERβ selectivity. However, C11 and C12 were ERα‐selective agonists. The position and substituent moiety of prenylation, C‐ring configuration, and flavonoid skeleton were important for the ER modulating activities. Hydrogen bonds between 3′‐OH and Leu339 in ERβ, and 5′‐OH and Glu305 in ERβ might respond for the higher agonistic activity of C8 and C10, respectively. C8, C9, C11, and C12 showed more potency than 17β‐estradiol on neuroprotection in glutamate‐treated PC‐12 cells. C8 and C12 could reverse reactive oxygen species overproduction and reduction of Δψm induced by glutamate through increase of the expression of ERS1 , SOD1 , SOD2 , CAT , and GPx4 and decrease of caspase‐3 expression, suggesting C8, and C9 might interact with ERα, promote antioxidant defense, mitigate oxidative stress, and improve mitochondrial function to exert the neuroprotection activities." @default.
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- W4386204120 date "2023-08-27" @default.
- W4386204120 modified "2023-10-04" @default.
- W4386204120 title "The estrogen receptor modulatory activity and neuroprotective activity of novel prenylated flavonoids and their structure–activity relationship" @default.
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- W4386204120 doi "https://doi.org/10.1002/fsh3.12018" @default.
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