ACTA PHARMACOLOGICA SINICA
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2021
·Vol. 42
·期 12
·1991-2003
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IF 6.15
Dong Wen-li,Zhong Jia-hong,Chen Yun-qing,Xie Jin-feng,Qin Yun-yun,Xu Jiang-ping,Cai Ning-bo,Li Meng-fan,Liu Lu,Wang Hai-tao
We have previously shown that roflupram (ROF) protects against MPP + -induced neuronal damage in models of Parkinson’s disease (PD). Since impaired degradation of α-synuclein (α-syn) is one of the key factors that lead to PD, here we investigated whether and how ROF affects the degradation of α-syn in rotenone (ROT)-induced PD models in vivo and in vitro. We showed that pretreatment with ROF (10 μM) significantly attenuated cell apoptosis and reduced the level of α-syn in ROT-treated SH-SY5Y cells. Furthermore, ROF significantly enhanced the lysosomal function, as evidenced by the increased levels of mature cathepsin D (CTSD) and lysosomal-associated membrane protein 1 (LAMP1) through increasing NAD + /NADH and the expression of sirtuin 1 (SIRT1). Pretreatment with an SIRT1 inhibitor selisistat (SELI, 10 μM) attenuated the neuroprotection of ROF, ROF-reduced expression of α-syn, and ROF-increased expression levels of LAMP1 and mature CTSD. Moreover, inhibition of CTSD by pepstatin A (20 μM) attenuated ROF-reduced expression of α-syn. In vivo study was conducted in mice exposed to ROT (10 mg·kg −1 ·d −1 , i.g.) for 6 weeks; then, ROT-treated mice received ROF (0.5, 1, or 2 mg·kg −1 ·d −1 ; i.g.) for four weeks. ROF significantly ameliorated motor deficits, which was accompanied by increased expression levels of tyrosine hydroxylase, SIRT1, mature CTSD, and LAMP1, and a reduced level of α-syn in the substantia nigra pars compacta. Taken together, these results demonstrate that ROF exerts a neuroprotective action and reduces the α-syn level in PD models. The mechanisms underlying ROF neuroprotective effects appear to be associated with NAD + /SIRT1-dependent activation of lysosomal function.
研究领域:
神经科学
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药理学
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细胞生物学
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高影响因子
Neural Regeneration Research
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2020
·
IF 3.171
Shuo Zhang,Yan Ma,Juan Feng
Trans-(-)-ε-viniferin (ε-viniferin) has antioxidative and anti-inflammatory effects. It also has neuroprotective effects in Huntington’s disease by activating the SIRT3/LKB1/AMPK signaling pathway; however, it remains unknown whether ε-viniferin also has a neuroprotective role in Parkinson’s disease. A Parkinson’s disease cell model was induced by exposing SH-SY5Y cells to 3.0 μM rotenone for 24 hours, and cells were then treated with 1.0 μM ε-viniferin for 24 hours. Treatment with ε-viniferin upregulated SIRT3 expression, which promoted FOXO3 deacetylation and nuclear localization. ε-Viniferin also increased ATP production and decreased reactive oxygen species production. Furthermore, ε-viniferin treatment alleviated rotenone-induced mitochondrial depolarization and reduced cell apoptosis, and restored the expression of mitochondrial homeostasis-related proteins. However, when cells were transfected with SIRT3 or FOXO3 shRNA prior to rotenone and ε-viniferin treatment, these changes were reversed. The results from the present study indicate that ε-viniferin enhances SIRT3-mediated FOXO3 deacetylation, reduces oxidative stress, and maintains mitochondrial homeostasis, thus inhibiting rotenone-induced cell apoptosis. ε-Viniferin may therefore be a promising treatment strategy for Parkinson’s disease.
研究领域:
神经科学
·
药理学
·
细胞生物学
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BIOMEDICAL CHROMATOGRAPHY
·
2025
·Vol. 40
·期 1
·e70320
·
IF 1.7
Ying Ma,Yu Yao,Yue Pu,Hong Chen,Juan Zhang
Parkinson's disease (PD) is a progressive neurodegenerative disorder marked by the loss of dopaminergic neurons in the substantia nigra and the pathological accumulation of α-synuclein (α-Syn). Rotenone, a mitochondrial complex I inhibitor, reliably reproduces these hallmark features and is therefore widely used to establish experimental PD models. Shiliuwei Kangchanzhijing capsules (SLW-KCZJ capsules), a traditional Chinese medicine (TCM) formulation comprising 16 herbal components, were specifically developed for PD management. This study systematically evaluated the neuroprotective effects and underlying mechanisms of SLW-KCZJ in a rotenone-induced PD mouse model. SLW-KCZJ treatment significantly improved movement distance and balance–coordination, attenuated neuronal loss in the substantia nigra, and markedly suppressed neuroinflammatory responses. At the molecular level, the capsules increased tyrosine hydroxylase expression by approximately 200% and elevated Parkin and protein phosphatase 2A levels by approximately 60% and 80%, respectively. In contrast, they robustly inhibited polo-like kinase 2 expression and reduced α-Syn levels by approximately 60% and 40%. The intervention also increased striatal dopamine (DA) and homovanillic acid levels while lowering neurofilament light chain and oligomeric α-Syn. In summary, this study provides the first evidence that SLW-KCZJ capsules exert neuroprotective effects by modulating the Parkin/PP2A/α-Syn signaling pathway, offering a promising TCM-based therapeutic strategy for PD.
研究领域:
神经科学
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药理学
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中医中药
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神经退行性疾病
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分子生物学
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PEST MANAGEMENT SCIENCE
·
2025
·
IF 3.8
Jiangtao Dong,Guoquan Wang,Yanli Zhao,Hexin Li,Haoming Li,Heng Zhang,Xinan Li,Li Xu,Feng Zhou,Runqiang Liu,Xinming Yin
BACKGROUND Pesticides in agriculture have played an important role and are irreplaceable in increasing the yield of crops and agricultural products. However, ultraviolet photodegradation is a crucial factor that leads to the inefficient usage of most traditional pesticides under sunlight. Rotenone (Rot), as a plant-derived insecticide, is easily degraded under ultraviolet light with loss of biological activity, which severely limits its wide application in the fields. It is therefore necessary to create new formulations to prevent the photodegradation of Rot under ultraviolet radiation. RESULTS Simple, intelligent, and degradable Rot@Fe III -tannic acid (Rot@Fe III -TA) nanocapsules were constructed using a general strategy, where Rot was coated in the core and Fe III -TA networks as the shell prepared via in situ coordination assembly on the interface of oil/water microemulsions. The prepared nanocapsules showed multidimensional stimuli-responsive controlled release performance, containing acidic/alkaline pH, glutathione, H 2 O 2 , and phosphate, which were closely relevant to the physiological environments of crops, and the Fe III -TA shell was finally disassembled in crops against bioaccumulation. Furthermore, the prepared nanocapsules showed remarkable rain washing and UV photolysis resistance on wheat leaf surface for availably wheat aphid control compared with that of technical Rot. In addition, the prepared nanocapsules appeared good safety on seed germination and seedling emergence, and were beneficial for the growth of wheat seedlings. CONCLUSION The prepared Rot@Fe III -TA nanocapsules could effectively prevent the photodegradation of Rot under ultraviolet radiation for wheat aphid control, which has potential application for Rot formulation exploitation in the field in the future. © 2025 Society of Chemical Industry.
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2026
·
IF 4.8
Jingxian Zhu,Bo Jing,Yiman Jia,Weiwei Zhang,Changyan Sun
Developing sensitive and biocompatible detection technologies is important for public health management and risk assessment. In this investigation, a new multifunctional Tb-MOF fluorescent nanomaterial was constructed, which has excellent structural stability and luminescent performance. It can achieve highly sensitive detection of three key target substances - aspartic acid, ethyl maltol, and rotenone in complex matrices, with detection limits as low as 16.0, 14.5, and 48.0 nM respectively. The Tb-MOF exhibited successful application in real samples such as infant formula, peanut oil, and artificial serum with satisfactory recovery rates (92.49%–103.1%). It is worth noting that the cytotoxicity experiment further confirmed its low toxicity, supporting its safe application in the biological body.
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危险品化学品经营许可证（带存储）