Jia-Jian-Di-Huang-Yin-Zi decoction reduces apoptosis induced by both mitochondrial and endoplasmic reticulum caspase12 pathways in the mouse model of Parkinson's disease

Ethnopharmacological relevance: As a classical prescription of traditional Chinese medicine (TCM), Jia-Jian-Di-Huang-Yin-Zi decoction (JJDHYZ) has been used to treat the symptoms of neurological disorders with a long history. Aim of the study: To evaluate the effects and possible mechanisms of JJDHYZ on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced subacute mouse model of Parkinson's disease. Materials and methods: Adult male C57BL/6 mice were randomly divided into five groups: control, MPTP, JJDHYZ low dosage (JJDHYZ-L, 8.5 g/kg/day), medium dosage (JJDHYZ-M, 17 g/kg/day) and high dosage (JJDHYZ-H, 34 g/kg/day). Behavioral tests, immunohistochemistry, immunofluorescence, and high-performance liquid chromatography (HPLC) were conducted to evaluate the neuroprotective effects of JJDHYZ. The mechanism was further explored using TdT-mediated dUTP nick end labeling staining and transmission electron microscopy. The protein expression of Bax, Bcl-2, cytochrome c, full-length caspase9, cleaved caspase9, cleaved caspase3, caspase12 and C/EBP homologous protein was assessed. The toxicity on hepatocytes and renal cells was detected using the enzyme-linked immunosorbent assay kits. Results: JJDHYZ-H restored the behavior performance impaired by MPTP, and reduced the loss of tyrosine hydroxylase. Additionally, it blocked the apoptosis, activated cleaved caspase3 and protected the ultrastructural integrity of mitochondria by regulating the expression of proteins in both mitochondrial and endoplasmic reticulum (ER) caspase12 pathways. Conclusions: JJDHYZ-H showed behavior recovery and dopamine neuron protection by inhibiting the apoptotic activities associated with mitochondrial and ER caspase12 pathways.