Investigation on the protective effect of Arisaema Cum Bile on MPTP-induced Parkinson’s disease model mice based on PKA signaling pathway
- VernacularTitle:基于PKA信号通路探讨胆南星对MPTP诱导帕金森病模型小鼠的保护作用
- Author:
Guien CHEN
1
;
Yafang DENG
1
;
Wanrou DENG
1
;
Binxi WU
1
;
Donghui PENG
2
;
Yuanning ZENG
1
,
2
;
Qiuhong WANG
1
Author Information
1. School of Chinese Materia Medica，Guangdong Pharmaceutical University/Guangdong Engineering Technology Research Center for Standardized Processing of Chinese Materia Medica，Guangzhou 510006，China
2. Heilongjiang Key Laboratory for Pharmacodynamic Material Bases of TCM and Natural Medicines/Key Laboratory of Northern Medicine Foundation and Application，Ministry of Education，Heilongjiang University of Chinese Medicine，Harbin 150040，China
- Publication Type:Journal Article
- Keywords:
Arisaema Cum Bile;
Parkinson’s disease;
1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine;
cAMP-dependent
- From:
China Pharmacy
2023;34(15):1809-1814
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the improvement effects of Arisaema Cum Bile on Parkinson’s disease （PD） model mice and its potential mechanism. METHODS Sixty male C57BL/6J mice were randomly divided into normal group， model group， Arisaema Cum Bile low-dose group [0.39 g/（kg·d）]， Arisaema Cum Bile high-dose group [1.56 g/（kg·d）] and positive control drug Levodopa tablet group [80 mg/（kg·d）]， with 12 mice in each group. Except that normal group was given constant volume of normal saline， other groups were given 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine [MPTP，35 mg/（kg·d）] intraperitoneally for 5 consecutive days to induce subacute PD model； after modeling， they were given relevant medicine continuously for 7 d； rod climbing test and line suspension test were performed 1 d before modeling， on the 5th day of modeling and after the last medication. The number of tyrosine hydroxylase （TH）-positive neurons in the substantia nigra of mice were measured by immunofluorescence； the levels of interleukin 1β （IL-1β） and tumor necrosis factor α（ TNF-α） in serum and the levels of IL- E-mail：qhwang668@sina.com 1β， TNF-α， cyclooxygenase-2 （COX-2） and inducible nitric oxide synthase （iNOS） in the substantia nigra of mice were measured by enzyme-linked immunosorbent assay. The expression levels of cAMP-dependent protein kinase catalytic subunit α （PKA C-α）， glutathione peroxidase 4 （GPX4） and ferritin heavy chain polypeptide 1 （FTH1） proteins in the substantia nigra of mice was measured by Western blot. RESULTS After last medicine， compared with the normal group， mice in the model group had significantly longer pole-climbing time （P＜0.01）， significantly lower line suspension scores （P＜0.01）， significantly fewer TH-positive neurons in the substantia nigra （P＜0.01）， significantly higher serum concentrations of IL-1β and TNF-α and nigrostriatal concentrations of IL-1β， TNF-α， COX-2 and iNOS （P＜0.01）， while lower protein expression levels of GPX4， PKA C-α and FTH1 in the substantia nigra （P＜0.05 or P＜0.01）. Compared with the model group， the above indexes of mice were significantly returned in Arisaema Cum Bile high-dose group （P＜0.05 or P＜ 0.01）. CONCLUSIONS Arisaema Cum Bile can improve motor impairment and reduce apoptosis of nigrostriatal TH neurons in MPTP-induced PD mice， and has neuroprotective effects on model mice； this may be related to its inhibition of neuroinflammation and the inhibition of ferroptosis by up-regulating PKA signaling pathway.
