1.Investigation on the protective effect of Arisaema Cum Bile on MPTP-induced Parkinson’s disease model mice based on PKA signaling pathway
Guien CHEN ; Yafang DENG ; Wanrou DENG ; Binxi WU ; Donghui PENG ; Yuanning ZENG ; Qiuhong WANG
China Pharmacy 2023;34(15):1809-1814
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.