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.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
Adult male C57BL/6 mice were randomly divided into five groups: control, MPTP, JJDHYZ low dosage (JJDHYZ-L, 8.5g/kg/day), medium dosage (JJDHYZ-M, 17g/kg/day) and high dosage (JJDHYZ-H, 34g/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.
Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Jingsi
J
Zhang
Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Zhennian
Z
Zhang
Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Jie
J
Bao
Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Zhonghai
Z
Yu
Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Min
M
Cai
Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Xiangting
X
Li
Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Ting
T
Wu
Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: xiang.jun@mail.zs-hospital.sh.cn.
Jun
J
Xiang
Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: dingfangcai@163.com.
Dingfang
D
Cai
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053454:Caspase 12 / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000503:physiopathology
D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; C582425:di huang yin zi; D053454:Caspase 12
Albiflorin (Pubchem CID: 24868421); Apoptosis; Catalpol (Pubchem CID: 91520); Cistanoside D (PubChem CID: 5315930); Echinacoside (PubChem CID: 5281771); Ferulic acid (Pubchem CID: 445858); Neurodegenerative disorders; Paeoniflorin (PubChem CID: 442534); Parkinson’s; Rehmannioside A (PubChem CID: 6325881); Rehmannioside D (PubChem CID: 92044472); Rubiadin (PubChem CID: 124062); Signal transduction; Traditional medicine Asia & Oceania; Ursolic acid (PubChem CID: 64945); Verbascose (Pubchem CID: 441434)