Abstract
This study aimed to explore the protective effects of Wenshen-Yanggan decoction on dopaminergic (DA) neuron injury in a rotenone-induced mouse model with chronic Parkinson's disease (PD) and explore its mechanism of action. Ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to measure the content of six main components in the Wenshen-Yanggan decoction. The chronic PD mouse model was established by treating 10-month-old healthy wild C57BL/6 male mice with rotenone 30 mg/kg/day for 28 days in succession. The pole test and rotarod test were applied to detect the rescue effect of Wenshen-Yanggan decoction in high, medium, and low dosages, respectively, on PD-like behaviors in mice with chronic PD. The protective effect of Wenshen-Yanggan decoction on the mesencephalic nigrostriatal DA neuron injury was determined employing tyrosine hydroxylase (TH) immunofluorescence staining. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the inflammatory cytokines in serum, including TNF-α (tumor necrosis factor-alpha), IFN-γ (interferon gamma), NF-κB (nuclear factor kappa-B), and IL-1β (interleukin-1 beta). Western blotting was performed to quantify the expression of phosphorylated c-Jun N-terminal kinase (p-JNK), cleaved caspase-3, B-cell lymphoma-2 (Bcl-2), and NF-κB in the brain. Our results showed that the Wenshen-Yanggan decoction in high, medium, and low dosages reduced the turning time of mice (P < 0.01, P < 0.01, and P < 0.05). The high and medium dosages shortened the total climbing time of PD mice in the pole test (P < 0.01 and P < 0.05). Meanwhile, the high, medium, and low dosages increased the rod-standing time of PD mice in the rotarod test (P < 0.01, P < 0.05, and P < 0.05). Besides, the decoction reversed the decrease in TH-positive neurons induced by rotenone, upregulated TH protein expression, and downregulated the α-syn expression in the PD model. Moreover, the decoction in high dosage significantly inhibited the expression of p-JNK, cleaved caspase-3, and NF-κB in the midbrain of PD mice (P < 0.05, P < 0.05, and P < 0.01), upregulated the expression of Bcl-2 (P < 0.05), and decreased the content of TNF-α, IFN-γ, NF-κB, and IL-1β in the serum (P < 0.001, P < 0.001, P < 0.001, and P < 0.001). Taken together, the Wenshen-Yanggan decoction could protect mice from rotenone-induced chronic PD, which might be related to the reduction of the DA neuron apoptosis via suppressing the inflammatory reaction and the neuronal apoptosis pathway.
Highlights
Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease
PD is a slowly progressive neurodegenerative disorder. e pathological changes of PD are characterized by the presence of substantia nigra pars compacta (SNpc) degeneration and the occurrence of Lewy body, which are related to autophagy, apoptosis, oxidative stress, and other complex mechanisms including immune response, inflammatory response, and excitotoxicity [15]. e focus of PD research studies is to study its etiology and develop therapies that possess disease-modifying effect and are able to slow down the disease process
The pathogenesis of PD is still unclear, it is believed that neuroinflammation is one of the main pathological mechanisms of PD and a potential target for PD treatment [16]
Summary
Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease It is characterized by progressive loss of dopamine (DA) neurons mainly in the substantia nigra pars compacta (SNpc) and the appearance of cytoplasmic inclusion, which is called Lewy bodies, and its main component is α-synuclein. Is toxin features high lipophilicity and can access dopaminergic neurons beyond the blood-brain barrier without any transporter [7] It is one of the neurotoxic drugs used to establish the neurotoxin model of PD in recent studies [8]. E Wenshen-Yanggan decoction is a formula used for PD treatment at Nanjing TCM Hospital, which is composed of Cistanches Herba, Paeoniae Radix Alba, Dioscoreae Rhizoma, Linderae Radix, Fructus Alpiniae Oxyphyllae, and Uncariae Ramulus Cum Uncis It has various functions, for instance, warming the kidney yang, nourishing the liver blood, and quenching the liver wind. Rotenone was used to elicit chronic PD in C57BL/6 mice
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