ZPT01, a three‑herb formulation, improved motor behavior and protected dopaminergic neurons in MPTP mice and, supported by docking and cell experiments, appears to act via restoring AKT phosphorylation and suppressing COX‑2/PTGS2‑mediated neuroinflammation.

This work provides preclinical evidence of a multi‑target neuroprotective and anti‑inflammatory candidate that engages translationally relevant pathways (AKT signaling and COX‑2) for PD, making it a promising starting point for further pharmacology, PK/PD, and safety studies despite the usual…

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and chronic neuroinflammation for which effective disease-modifying treatments remain limited. Increasing evidence suggests that herbal extracts can modulate multiple pathological pathways involved in PD. In this study, we developed a novel herbal formulation, ZPT01, and investigated its therapeutic potential using an integrated approach combining in vivo, in vitro, and in silico analyses. METHODS AND RESULTS: In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse models, ZPT01 administration improved motor symptoms, protected dopaminergic neurons, and alleviated neuroinflammatory responses. Network pharmacology analysis identified AKT serine/threonine kinase 1 (AKT1) and prostaglandin-endoperoxide synthase 2 (PTGS2) as key molecular targets, and subsequent molecular docking demonstrated a strong binding affinity between the active compounds and these targets. In vitro experiments further validated these findings, showing that ZPT01 restored the phosphorylation of AKT, a protein product of the AKT1 gene, in 1-methyl-4-phenylpyridinium-exposed PC12 cells and suppressed cyclooxygenase-2 (the protein encoded by PTGS2) expression in lipopolysaccharide-stimulated BV2 microglia. CONCLUSIONS: Our study highlights the neuroprotective and anti-inflammatory properties of ZPT01 and provides promising evidence for its potential as a therapeutic candidate for PD.