Pseudolaric acids A and B show neuroprotective signals in cells and an AlCl3 Alzheimer's mouse model
- Pseudolaric acids A and B were tested against Aβ25–35-induced PC12 apoptosis and LPS-stimulated BV2 microglia and RAW264.7 macrophages.
- In vitro, anti-apoptotic effects were linked to IRS-1/Akt/GSK-3β signaling and anti-inflammatory effects to NF-κB and miR-155.
- In an AlCl3-induced mouse model, pseudolaric acid B improved spatial learning and memory in the water maze.
💡 Points Based on the abstract
Weak translational chain: Aβ25–35 on PC12 cells and an aluminium-chloride mouse are poor predictors of human Alzheimer's, and the authors concede the mechanisms are not confirmed in vivo. Pseudolaric acid B is also a cytotoxic microtubule-destabilising agent, so the window between neuroprotective and toxic exposure, plus any brain penetration data, matters more than another pathway readout. A transgenic model with PK would be the next step.