Yang Zhao

One of the main pathological features of Parkinson's disease (PD) is the loss of dopaminergic neurons in the substantia nigra compacta (SNc). Cistanoside A (CA) has a strong neuroprotective effect in PD, but the exact mechanism is unclear. In the present study, the MPTP‐stimulated mouse model of PD and MPP⁺‐treated PD model in the MES23.5 neuronal cell model of PD were used to investigate the neuroprotective effects of CA on PD and its potential mechanism. The in vivo experiment results indicated that CA improved the motor function in mice and increased the number of tyrosine hydroxylase positive cells in SNc. In vitro experiments showed that CA reduced the MPP⁺‐induced decrease in neurons and mitochondrial membrane potential and promoted the activation of autophagosomes. Furthermore, we found that CA promoted the recruitment of PINK1 and Parkin aggregation to impair mitochondrial membranes and inhibited mitochondrial damage via LC3‐ and p62‐mediated autophagy. In conclusion, CA protects against MPTP‐induced neurotoxicity in vivo and MPP⁺‐induced neurotoxicity in vitro, possibly by promoting the PINK1/Parkin/p62 pathway to accelerate the degradation of damaged mitochondria thereby reducing oxidative stress.

Parkinson's disease (PD), the typical neurodegenerative disease, is characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN). However, no therapeutic agent used currently could slow down neuronal cell loss so as to decelerate or halt the progression of PD. Traditional Chinese medicine (TCM) has been utilized to treat the dysfunction of the autonomic nervous system. Wen-Shen-Yang-Gan decoction (WSYGD) has a good effect on the clinical treatment of PD with constipation. However, it is not clear which ingredients and what mechanism are responsible for the therapeutic effect. In this study, the pharmacodynamic study of WSYGD in PD mice was applied. Concurrently, a novel method for the identification of metabolic profiles of WSYGD has been developed. Finally, we found that WSYGD could protect the PD mice induced by rotenone. The underlying mechanism of the protective effect may be related to the reduction of the DA neurons apoptosis via reducing inflammatory reaction. By virtue of UPLC-MS and chemoinformatics method, 35 prototype compounds and 27 metabolites were filtered out and tentatively characterized. In conclusion, this study provides an insight into the metabolism of WSYGD in vivo to enable understanding of the metabolic process and therapeutic mechanism of PD.

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.

Osteoarthritis (OA) is a degenerative joint disease which is one of the most frequent and disabling diseases encountered in elderly individuals. Leptin was unregulated significantly in OA cartilage and was regarded as a metabolic link between obesity and OA. In this study, we evaluated the effect of 10 or 100 ng/ml leptin on the ATDC5 cells. Results revealed that 10 or 100 ng/ml of leptin significantly decrease the expression of aggrecan and type II collagen mRNA and protein levels compare to control (0 ng/ml). Interestingly, sex determining region Y-box 9 mRNA and protein was down-regulated by leptin. Collagen X is a specific marker of hypertrophic and calcified chondrocyte. It has been noted that both mRNA and protein of Collagen X was significantly upregulated with leptin treatment. Meanwhile, Alcian Blue staining indicated that leptin reduces the synthesis of proteoglycan. Alizarin red S staining and alkaline phosphatase activity detection demonstrated that leptin induced cartilage nodules formation and mineralization in a dose dependent manner. We conclude that leptin slightly inhibits the proliferation of ATDC5 cells and affects cartilage-specifically marked proteins and genes. In summary, it has been suggested that leptin stimulate hypertrophic differentiation of ATDC5 cells.