A Docking-Guided Strategy Prioritizes Parishin B as a Potential Anti-Alzheimer’s Constituent of Gastrodia elata Blume

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with limited treatment options. Phosphodiesterase 4B (PDE4B) is a key regulator of neuroinflammation and has been implicated in AD pathology. Using molecular docking against PDE4B as a screening anchor, we analyzed constituents from G. elata water extract and identified Parishin B as a top-ranked candidate. Parishin B directly inhibited recombinant PDE4B, reducing activity to 22.1% of control at 100 μM. In an Al3+-induced zebrafish AD model, both the crude extract and purified Parishin B significantly rescued behavioral deficits; Parishin B at 100 μM showed no statistical difference from the donepezil group, while the crude extract was effective at 30 μg/mL. Mechanistically, Parishin B protected SH-SY5Y neurons against H2O2-induced oxidative stress by reducing ROS and apoptosis and suppressed LPS-induced neuroinflammation in BV-2 microglia via downregulation of iNOS and COX-2. These results suggest that Parishin B is a chemically traceable constituent with dual neuroprotective actions, validating the docking-guided screening strategy and supporting further investigation of G. elata as a source of AD-relevant bioactive compounds.