Introduction: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline; recent studies suggest that neuronal ferroptosis plays a key role in its pathogenesis. Danggui Shaoyao San (DSS), a traditional Chinese medicine formula, has shown demonstrated neuroprotective effects, but its precise mechanisms in AD treatment remain unclear. This study aims to investigate the mechanism of DSS in treating AD by inhibiting neuronal ferroptosis, explore whether DSS alleviates AD by suppressing neuronal ferroptosis via the AMPK/Sp1/ACSL4 pathway.Methods: Chemical composition of DSS was identified by LC-MS/MS, followed by network pharmacology to predict targets and pathways. Molecular docking assessed binding affinities between DSS compounds and key proteins (AMPK, Sp1, ACSL4). In vivo experiments on APP/PS1 mice evaluated DSS effects on cognitive function, oxidative stress markers, lipid peroxidation, and ferroptosis-related proteins.Results: Network pharmacology analysis suggested that DSS regulates lipid metabolism and inhibits neuronal ferroptosis via the AMPK pathway. Molecular docking revealed strong binding affinities between DSS compounds and AMPK downstream proteins, Sp1 and ACSL4. In vivo experiments showed that DSS improved cognitive function, enhanced antioxidant capacity, reduced lipid peroxide accumulation, and decreased Fe2+ content in brain tissue. Furthermore, DSS increased the expression of FTH, p-AMPK, and GPX4 while decreasing Sp1 and ACSL4 levels, thereby inhibiting ferroptosis.Conclusion: DSS alleviates AD symptoms by suppressing neuronal ferroptosis via the AMPK/Sp1/ACSL4 axis, representing a novel lipid metabolism-targeted therapeutic strategy.
This study elucidated the chemical composition of essential oil from Centipeda minima (EOCM) and its antibacterial and antioxidant activities with two chemical monomers thymol and carvacrol. The main chemical composition of EOCM, analyzed by GC-MS, were trans-chrysanthenyl acetate, thymol, aromadendrene and β-caryophyllene. In the screening of antibacterial activity against S. aureus, two monomers with antibacterial activity were obtained: thymol and carvacrol. The MIC of EOCM, thymol and carvacrol were 0.625 mg/mL, 0.156 mg/mL and 0.156 mg/mL, respectively. The experimental results were shown that three drugs could inhibit the growth of S. aureus and inhibit the formation of biofilm by changing the permeability of cell membrane and interfering with the metabolic activities in bacteria. The scavenging effects of the three drugs on DPPH radical and hydroxyl radical showed that the antioxidant effect of the three drugs was EOCM > carvacrol > thymol.