Nardosinone Alleviates Parkinson's Disease Symptoms in Mice by Regulating Dopamine D2 Receptor

Nardostachyos Radix et Rhizoma (nardostachys) is the root and rhizome of Nardostachys jatamansi DC. Recent studies have shown that nardostachys may exert an anti-PD effect. In this study, the UHPLC-LTQ-Orbitrap-MS method was used to analyze the brain components of nardostachys in rats. Based on the results of UHPLC-LTQ-Orbitrap-MS analysis, nardosinone was identified to be the most effective anti-PD compound in nardostachys. To further verify this inference, a mouse PD model was established and the effect of nardosinone on PD mice was determined using classic behavioral tests. The results showed that nardosinone was indeed effective for relieving PD symptoms in mice. Moreover, network pharmacology analysis was used to elucidate the mechanism underlying the anti-PD effect of nardosinone. Dopamine receptor D2 (DRD2) was identified as the key target of nardosinone-PD interaction network, which was further verified by molecular docking and Western blotting. The results demonstrated that nardosinone and DRD2 could interact with each other. Furthermore, the expression level of DRD2 was decreased in the brain tissue of PD mice, and nardosinone could restore its expression to a certain extent. In conclusion, our findings suggest that nardosinone may reduce the motor and cognitive symptoms in the animal PD model by regulating DRD2 expression.