Total Glucosides of White Paeony Capsule ameliorates Parkinson's disease-like behavior in MPTP-induced mice model by regulating LRRK2/alpha-synuclein signaling

Ethnopharmacological relevance: The Total Glucosides of White Paeony Capsule (TGPC), one of the traditional Chinese patent medicines, has been used for the treatment of autoimmune diseases such as rheumatoid arthritis (RA) in clinical practice. Besides, the components of TGPC are extracted from Radix Paeoniae Alba (RPA) and have displayed neuroprotective properties. Aim of the study: The present study was designed to evaluate the anti-PD-like effects of TGPC on a 1-methyl-4phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced mice model and explore its potential molecular mechanisms. Materials and methods: Behavioral tests, hematoxylin and eosin (HE) staining, Nissl staining, immunohistochemistry (IHC), western blotting (WB) and Enzyme-Linked Immunosorbent Assay (ELISA) were performed in this study. Results: It was observed that TGPC treatment (150, 300 mg/kg) significantly reversed MPTPinduced PD-like behaviors, such as reduced locomotive activity in the open field test, prolonged time to turn downward on the ball (T-turn) and to climb down the whole pole (T-descend) in the pole test, decreased movement scores in the traction test and extended the latency to fall in the hanging wire test. In addition, TGPC improved neurodegeneration, inhibited the excessive activation of microglia and suppressed the overproduction of proinflammatory cytokines induced by MPTP, partially by restoring leucine-rich repeat kinase 2 (LRRK2) activity and inhibiting alpha-synuclein (alpha-syn) mediated neuroinflammation signaling. Conclusion: Taken together, TGPC exhibited neuroprotective effects on MPTP-induced mice model of PD, which was associated with the prevention of neuroinflammation and neurodegeneration modulated by LRRK2/alpha-syn pathway.