Delphinidin attenuates cognitive deficits and pathology of Alzheimer's disease by preventing microglial senescence via AMPK/SIRT1 pathway.
Level 5 - mechanism / opinion, no new human data
Preclinical animal and in vitro cellular research with no human clinical data
PubMed 40542425 · doi:10.1186/s13195-025-01783-x
What was done
The authors investigated whether delphinidin, a naturally occurring anthocyanin, reduces Alzheimer's disease pathology by targeting microglial senescence. The study used APP/PS1 transgenic mice, naturally aged mice, and an in vitro model of Aβ42-induced senescent BV2 microglia. Assessments included cognitive performance, synapse loss, Aβ plaque burden, senescent microglia gene signatures, and cellular senescence markers (senescence-associated β-galactosidase activity, SASP factors, oxidative stress, and p21/p16 expression). Mechanism was probed via AMPK/SIRT1 pathway activation, direct delphinidin-SIRT1 interaction testing, and inhibition using the AMPK inhibitor Compound C.
What was found
The abstract reports no numerical values, effect sizes, or confidence intervals. Delphinidin treatment was reported to alleviate cognitive deficits, synapse loss, and Aβ plaque burden in APP/PS1 mice, while downregulating senescent microglial gene signatures and reducing senescence-associated β-galactosidase activity, SASP factors, oxidative stress, and p21/p16 levels. Delphinidin also prevented microglial senescence in naturally aged mice and in Aβ42-exposed BV2 microglia in vitro. Mechanistically, delphinidin directly interacted with SIRT1, enhanced AMPK/SIRT1 signaling, and its protective effect was reversed by Compound C.
Why it matters
This work identifies delphinidin as a potential natural candidate for reducing microglial senescence and Alzheimer's-related pathology in preclinical models.
Limits
The study is entirely preclinical, relying on rodent models and an immortalized cell line with no human participants. The abstract does not provide sample sizes, dosages, or quantitative outcome metrics.
Cited by
- context Clinical trials demonstrate that the anthocyanin delphinidin improves cognitive function and blood sugar levels.