Wuzi Yanzong Pill Plays A Neuroprotective Role in Parkinson's Disease Mice via Regulating Unfolded Protein Response Mediated by Endoplasmic Reticulum Stress

Objective To investigate the protective effects and its possible mechanism of Wuzi Yanzong Pill (WYP) on Parkinson's disease (PD) model mice. Methods Thirty-six C57BL/6 male mice were randomly assigned to 3 groups including normal, PD, and PD+WYP groups, 12 mice in each group. One week of intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish the classical PD model in mice. Meanwhile, mice in the PD+WYP group were administrated with 16 g/kg WYP, twice daily by gavage. After 14 days of administration, gait test, open field test and pole test were measured to evaluate the movement function. Tyrosine hydroxylase (TH) neurons in substantia nigra of midbrain and binding immunoglobulin heavy chain protein (GRP78) in striatum and cortex were observed by immunohistochemistry. The levels of TH, GRP78, p-PERK, p-eIF2 alpha, ATF4, p-IRE1 alpha, XBP1, ATF6, CHOP, ASK1, p-JNK, Caspase-12, -9 and -3 in brain were detected by Western blot. Results Compared with the PD group, WYP treatment ameliorated gait balance ability in PD mice (P<0.05). Similarly, WYP increased the total distance and average speed (PP<0.01), reduced rest time and pole time (P<0.05). Moreover, WYP significantly increased TH positive cells (P<0.01). Immunofluorescence showed WYP attenuated the levels of GRP78 in striatum and cortex. Meanwhile, WYP treatment significantly decreased the protein expressions of GRP78, p-PERK, p-eIF2 alpha, ATF4, p-IRE1 alpha, XBP1, CHOP, Caspase-12 and Caspase-9 (PP<0.01). Conclusions WYP ameliorated motor symptoms and pathological lesion of PD mice, which may be related to the regulation of unfolded protein response-mediated signaling pathway and inhibiting the endoplasmic reticulum stress-mediated neuronal apoptosis pathway.