Anti-apoptotic effect of Shudipingchan granule in the substantia nigra of rat models of Parkinson′s disease

Abstract

Levodopa is the gold-standard treatment for Parkinson′s disease. However, although it alleviates the clinical symptoms, it cannot delay the progressive apoptosis of dopaminergic neurons or prevent motor complications in the long term. In the present study, we investigated the effect of Shudipingchan granule on neuronal apoptosis in a rat model of Parkinson′s disease, established by injecting 6-hydroxydopamine into the substantia nigra pars compacta and ventral tegmental area. We then administered levodopa (20 mg/kg intraperitoneally, twice daily) with or without Shudipingchan granule (7.5 mL/kg intragastrically, twice daily), for 4 weeks. The long-term use of levodopa accelerated apoptosis of nigral cells and worsened behavioral symptoms by activating the extracellular signal-regulated kinase pathway and downstream apoptotic factors. However, administration of Shudipingchan granule with levodopa reduced expression of phosphorylated extracellular signal-regulated kinase 1/2 and Bax, increased tyrosine hydroxylase and Bcl-2, reduced apoptosis in the substantia nigra, and markedly improved dyskinesia. These findings suggest that Shudipingchan granule suppresses neuronal apoptosis by inhibiting the hyperphosphorylation of extracellular signal-regulated kinase and downregulating expression of anti-apoptotic genes. Shudipingchan granule, used in combination with levodopa, can effectively reduce the symptoms of Parkinson′s disease.

Keywords

• nerve regeneration; Parkinson′s disease; levodopa; substantia nigra; apoptosis; Shudipingchan granule; extracellular signal-regulated kinase pathway; behavior; neural regeneration