Mechanistically, PUN alleviated the progression of PD in rats exposed to SI with MnCl2 primarily by modulating HMGB1/RAGE/TLR4/NF-κB/NLRP3/Caspase-1, JAK-2/STAT-3, PI3K/AKT/GSK-3β/CREB, AMPK/SIRT-1, Nrf2/HO-1, and PERK/CHOP/Bcl-2 pathways (as shown in Graphical abstract). Here, TLR4 is linked to Parkinson disease.