Investigating the Therapeutic Potential of Rehmanniae Radix and
Rehmanniae Radix Praeparata in Alzheimer’s Disease: A Multi-Omics
Approach
Abstract
Background and Purpose Alzheimer’s disease (AD), a progressive
neurological disorder that causes memory decline and cognitive
dysfunction, increasingly threatens human health. Rehmanniae Radix
Praeparata (RRP) is derived from the steamed or wine-steamed
Scrophulariaceae plant, Rehmannia glutinosa Libosch. (RR). They show
promise in the treatment of AD, yet the variations in medical components
and their mechanisms of action against AD remain unclear. Experimental
Approach This study initially used APP/PS1 mice as AD animal models and
used UPLC-QE-MS/MS, network pharmacology, proteomics, 16S rRNA
sequencing to investigate differences in the medical components and
mechanisms of action of RR and RRP in treating AD. Results UPLC-QE-MS/MS
screening revealed that ajugol was the effective medicinal component of
RR for AD treatment, and isoacteoside was that of RRP. Integrated
multi-omics analyses predicted the involvement of the neuroinflammatory
pathway, apoptosis pathway, and autophagy pathway in the mechanisms of
the two ingredients for AD treatment. Subsequent in vivo and in vitro
experiments confirmed that RR and its active component, ajugol,
primarily modulated TLR/NF-κB/NLRP3 neuroinflammatory pathway and
Bcl-2/Bax/Cytochrome C/Caspase-3 apoptosis pathway, whereas RRP and its
active component isoacteoside predominantly affected
LC3-Ⅱ/P62/p-mTOR/mTOR autophagy pathway. These components collectively
improved cognitive deficits in AD mice, reduced Aβ plaque deposition in
brain tissue, and diminished BV2 microglial cell cytotoxicity in the
inflammation model, thereby ameliorating the progression of AD.
Conclusion This study systematically elucidated the distinctions in the
medical components and biological mechanisms of RR and RRP in treating
AD, revealing that the unique processing of TCM is key to its efficacy.