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Background Parkinson’s disease (PD) is caused by the gradual loss of dopamine-producing cells in the brain. This study evaluated the potential neuroprotective role of puerarin (PR) on dopamine (DA)-producing cells in vitro and in vivo . Method In vitro , the effects of PR on proliferation and differentiation and DA releases of mesenchymal stem cells (MSCs) were assayed by CCK-8, flow cytometry, real-time PCR and ELISA respectively. Then the differentiated cells were labeled with enhanced green fluorescent protein (EGFP) and administrated into PD animal models induced by 6-OHDA. The proliferation and differentiation of labeled cells were identified by fluorescence microscopy and immunostaining. Results In vitro , after being treated with different concentrations of PR for 1 week, the TUJ1, TH and DAT protein and mRNA expression and DA releases increased significantly. In vivo , after transplantation of PR-treated DA-producing cells, the symptoms of PD improved significantly from the second week after transplantation; more transplanted cells survived and migrated to wider region along injection line; more transplanted cells proliferated and differentiated into TH + cells; more DA was detected in the striatum during 6 weeks’ observation. Conclusion The results suggest that PR promote DA neuron survival, proliferation and differentiation. [ABSTRACT FROM AUTHOR]