Paeoniflorin alleviates neuroinflammatory response by suppressing HMGB1/RAGE pathway activation in MPTP induced mouse PD model

Abstract

Abstract Background Numerous studies have highlighted that Paeoniflorin (PF) exerts various biological effects, including anti-inflammatory, antioxidative, and anti-apoptotic actions on Parkinson’s disease (PD). However, the underlying anti-inflammatory mechanism of PF on PD is still not fully understood. Methods In present study, we assumed that the neuroprotective effect and anti-inflammatory mechanism of PF occurs through modulating HMGB1/RAGE pathway. We verified this hypothesis on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)/1-Methyl-4-Phenylpyridinium Iodide (MPP+) induced PD model of mice and BV-2 cells. We performed behavioral tests (pole test, beam-cross test and traction test) to investigate the motor function, the protein level of tyrosine hydroxylase (TH) and the aggregation of microglia were evaluated by immunostaining. The pro-inflammatory cytokines and the expression of HMGB1, RAGE, and NF-κB were evaluated via ELISA and Western blot analyses respectively. Results The results showed that PF treatment could significantly improve motor function of PD mice in behavioral tests. Our data also revealed that PF could rescue dopamine neuron loss, inhibit the aggregation of microglial cells in the substantia nigra pars compacta in immunostaining, and lower the levels of pro-inflammatory cytokines in ELISA test. Both in vitro and in vivo experiments demonstrated that PF downregulates the expression of HMGB1, RAGE, and NF-κB in the PD models induced by MPTP/MPP+. Conclusion In this study, PF exerted neuroprotective effects on PD models by downregulating the activation of HMGB1/RAGE/NF-κB pathway to reduce neuroinflammatory response.