NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2020
·Vol. 393
·期 9
·1739-1752
·
IF 2.05
Song Lin,Yao Lifen,Zhang Limei,Piao Zhongyuan,Lu Yichan
Autophagy, a lysosomal degradative pathway, is crucial for the pathogenesis of Alzheimer’s disease (AD). Schizandrol A (SchA) shows multiple pharmacological effects. However, the potential effects and mechanisms of SchA on amyloid-β (Aβ)-induced autophagy remain unclear. In this study, differentiated SH-SY5Y cells or primary hippocampal neurons were pretreated with SchA (2 μg/ml) for 1 h before subjected to Aβ 1–42 (10 μM) for 24 h to test its effects on cell viability, apoptosis, oxidative stress, and autophagy. Then an mTOR inhibitor (rapamycin) and a PI3K inhibitor (LY294002) were employed to explore the role of PI3K/AKT/mTOR pathway. The results showed that SchA significantly inhibited Aβ 1–42 -triggered reduction of viable cells, increases of apoptotic cell number and pro-apoptotic protein expressions, as well as alterations of oxidative stress markers. In addition, the increases of LC3-II/LC3-I and Beclin-1 and decrease of p62 were suppressed by SchA. At the molecular level, we found that the inactivation of PI3K/AKT/mTOR pathway was ameliorated by SchA. Inhibition of PI3K/AKT/mTOR pathway deteriorated the protective effects of SchA against Aβ 1–42 -induced autophagy activation, cell death, and apoptosis. In conclusion, we demonstrate that SchA attenuates Aβ 1–42 -induced autophagy through activating PI3K/AKT/mTOR signaling pathway. SchA may be a novel drug for the prevention and treatment of AD.
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高影响因子
Antioxidants
·
2025
·Vol. 14
·期 4
·490
·
IF 6.6
Chao Ma,Yu Nie,Donglei Zhang,Lulu Ran,Su Xu,Xun Ran,Junya Huang,Lingshuai Meng
Background: Blueberry anthocyanin such as Cyanidin-3-O-glucoside may help prevent Alzheimer’s disease. We aimed to investigate the preventive and therapeutic effects of Cyanidin-3-O-glucoside against Aβ1–42-induced apoptosis of SH-SY5Y cells as well as the underlying mechanisms. Methods: Cell viability and intracellular and mitochondrial reactive oxygen species were detected by MTT, a reactive oxygen species detection kit, and a MitoSOX red mitochondrial superoxide indicator. The mitochondrial membrane potential, intracellular calcium ion content, and adenotriphophate (ATP) were identified via a mitochondrial membrane potential detection kit, calcium ion detection kit, and ATP detection kit, and apoptosis was detected via flow cytometry. Transcription of apoptosis-related genes was detected using real-time fluorescence quantitative polymerase chain reaction, and expression of apoptosis-related proteins was identified using Western blot. Results: We found that Cyanidin-3-O-glucoside could downregulate the expression of cytochrome c, caspase 9, caspase 3, and other genes and proteins, which consequently reduced the rate of apoptosis. Additionally, it could upregulate Bcl-2 gene and protein expression, downregulate Bax gene and protein expression, regulate mitochondrial membrane permeability and calcium-release channels, reduce calcium influx into mitochondria, maintain intracellular calcium ion levels, reduce intracellular levels of reactive oxygen species and increase ATP levels, maintain the mitochondrial membrane potential at a normal level, maintain normal mitochondrial functioning, and prevent apoptosis. Discussion: Taken together, Cyanidin-3-O-glucoside showed dose-dependent preventive and therapeutic effects against Aβ1–42-induced apoptosis of SH-SY5Y cells. Conclusions: Cyanidin 3-O-glucoside showed a better preventive effect than therapeutic effect against Aβ1–42-induced apoptosis in SH-SY5Y cells.
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PHARMACEUTICAL CHEMISTRY JOURNAL
·
2023
·Vol. 57
·期 5
·712-724
·
IF 0.9
Li Danqi,Li Weihong,Shi Wenhao,Wu XiaoJing,Liu Xuegui,Gao Pinyi
Depression is a common mental health disease, with the characteristics of significant and persistent low mood. Traditionally, Ziziphus jujuba Mill . was used to treat depression. However, its chemical pharmacologic profiles remain to be elucidated. The present study was aimed to explore the potential targets and mechanisms of Z. jujuba in the treatment of depression using network pharmacology and in vitro neuroprotective experiment. In this study, 11 compounds of Z. jujuba were obtained by multiple column chromatography. Based on the network pharmacology, the C-T network was established by the results of molecular docking. The information on target proteins was enriched via DAVID database, followed by the analysis of GO and KEGG. The results indicated that 10 compounds, 5 target proteins and 3 signaling pathways played important roles in treating depression. Based on the predicted result of network pharmacology, compounds 1 , 9 and 10 were identified with significant neuroprotective effects by in vitro cell experiments with human neuroblastoma cell line SH-SY5Y. This study was the first to investigate the mechanisms of Z. jujuba action in the treatment of depression from the system level, and could provide the basis of the mechanism with action of compounds for the in-depth utilization of Z. jujuba.
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MICROCHEMICAL JOURNAL
·
2026
·
IF 5.2
Fanying Deng,Jinhong Xue,Yu Wang,Yue Sun,Peng Jiang,Yumeng Luo,Zhenqiang Liu,Zhichao Hao,Mengmeng Li,Wei Guan,Qingshan Chen,Lili Zhang,Xiaochi Ma,Haixue Kuang,Yan Liu
Extraction of Paeoniae Radix Rubra polysaccharide (PRRP). • Firstly, the PRRP was extracted by Natural Deep Eutectic Solvent (NADES). • Firstly, the PRRP was extracted by ChCl-CA (1.5, 3:2) with 40% ( w / w ) water. • AGREEprep and BAGI confirmed ChCl-CA’s greenness: polysaccharide yield >9%, solvent recovery >80%. • Firstly, the neuroprotective activity of PRRP in Parkinson's disease was evaluated. Firstly, natural deep eutectic solvents (NADES) were used to extract polysaccharides from Paeoniae Radix Rubra (PRR). Using polysaccharide yield and neuroprotective cell activity as evaluation criteria, a solvent composed of 40% ( w / w ) water, choline chloride (ChCl), and citric acid (CA) was selected as the optimal solvent. It exhibited low viscosity, high surface tension, moderate polarity, and strong acidity. Fourier-transform infrared (FT-IR) spectra of the ChCl-CA confirmed the formation of hydrogen bonding. Response surface methodology (RSM) optimized conditions: molar ratio: 1.5 (3:2), extraction temperature: 60 °C, extraction duration: 64 min, solvent-solid ratio: 36 mL·g −1 , the polysaccharide yield reached 16.74%, which was 1.89 times that of the hot water extraction, and the SH-SY5Y cell activity in the methyl-4-phenylpyridinium (MPP + )-induced PD model was 86.86%. The obtained PRR polysaccharides (PRRP) were further characterized, with protein content of 5.23% and uronic acid content of 19.09%. PRRP was mainly composed of arabinose, glucose, and galacturonic acid. Its molecular weights are 73.381, 11.475, and 3.539 kDa. PRRP was characterized via Ultraviolet-Visible (UV–Vis) and FT-IR spectroscopy, confirming typical polysaccharide structures. After 6 cycles, the polysaccharide yield of recycled NADES decreased from 16.26% to 9.22% in the final extraction, a 43.30% decrease. Two classical green evaluation models quantitatively confirmed the process's environmental friendliness. In addition, in vitro experiments showed that PRRP could increase dopamine (DA) and tyrosine hydroxylase (TH) levels, reduce lactate dehydrogenase (LDH) release, and decrease α -synuclein ( α -Syn) accumulation. This study highlights the efficiency of ChCl-CA as a green extractant and reveals the neuroprotective effect of PRRP. Download: Download high-res image (162KB) Download: Download full-size image Graphical abstract created in BioRender. com
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Antioxidants
·
2022
·Vol. 11
·期 5
·908
·
IF 7.675
Yuan Zhang,Tun Sun,Meng Li,Yanling Lin,Yue Liu,Shusheng Tang,Chongshan Dai
Ivermectin (IVM) could cause potential neurotoxicity; however, the precise molecular mechanisms remain unclear. This study explores the cytotoxicity of IVM in human neuroblastoma (SH-SY5Y) cells and the underlying molecular mechanisms. The results show that IVM treatment (2.5–15 μM) for 24 h could induce dose-dependent cell death in SH-SY5Y cells. Compared to the control, IVM treatment significantly promoted the production of ROS, mitochondrial dysfunction, and cell apoptosis. IVM treatment also promoted mitophagy and autophagy, which were charactered by the decreased expression of phosphorylation (p)-Akt and p-mTOR proteins, increased expression of LC3II, Beclin1, ATG5, PINK, and Pakin1 proteins and autophagosome formation. N-acetylcysteine treatment significantly inhibited the IVM-induced production of ROS and cell death in SH-SY5Y cells. Autophagy inhibitor (e.g., 3-methyladenine) treatment significantly inhibited IVM-induced autophagy, oxidative stress, and cell apoptosis. Taken together, our results reveal that IVM could induce autophagy and apoptotic cell death in SH-SY5Y cells, which involved the production of ROS, activation of mitochondrial pathway, and inhibition of Akt/mTOR pathway. Autophagy inhibition improved IVM-induced oxidative stress and apoptotic cell death in SH-SY5Y cells. This current study provides new insights into understanding the molecular mechanism of IVM-induced neurotoxicity and facilitates the discovery of potential neuroprotective agents.Keywords:ivermectin;neurotoxicity;oxidative stress;apoptosis;autophagy;Akt/mTOR pathway
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高影响因子
TOXICOLOGY LETTERS
·
2018
·
IF 3.166
Lin Li,Jiahui Cui,Zi Liu,Xuejiao Zhou,Zengqiang Li,Yang Yu,Yuanyuan Jia,Daiying Zuo,Yingliang Wu
Silver nanoparticles (AgNPs) have many medical and commercial applications, but their effects on human health are poorly understood. The aim of this study was to assess the effect of AgNPs on the human neuroblastoma cell line SH-SY5Y and to explore their potential mechanisms of action. We found that AgNPs decreased SH-SY5Y cell viability in a dose- and time-dependent manner. Exposure to AgNPs activated endoplasmic reticulum (ER) stress, as reflected by upregulated expression of glucose-regulated protein 78 (GRP78), phosphorylated PKR-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α), C/EBP homology protein (CHOP), spliced X-box binding protein-1 (XBP1), and phosphorylated inositol-requiring enzyme (p-IRE), all of which are involved in the cellular unfolded protein response. Prolonged exposure of cells to AgNPs damaged calcium (Ca 2+ ) homeostasis, increased the length of contact sites between the ER and mitochondria, altered IP 3 R function by the increased levels of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in the ER and enhanced mitochondrial Ca 2+ uptake. Finally, Ca 2+ overload and disrupted homeostasis in the mitochondria triggered apoptotic cell death. Our results suggest that caution should be exercised in the use of AgNPs in humans.
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危险品化学品经营许可证（带存储）