CHINESE JOURNAL OF PHYSIOLOGY
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2023
·Vol. 66
·期 6
·437
·
IF 1.8
Fan Wenbo,Zhou Jianwu
Parkinson's disease (PD) is recognized as a degenerative and debilitating neurodegenerative disorder. The novel protective role of icariside II (ICS II) as a plant-derived flavonoid compound in neurodegenerative diseases has aroused much attention. Herein, the definite impacts of ICS II on the process of PD and the relevant action mechanism were studied. Human neuroblastoma SK-N-SH cells were challenged with 1-methyl-4-phenylpyridinium ion (MPP + ) to construct the PD cell model. MTT assay and flow cytometry analysis, respectively, appraised cell viability and apoptosis. Caspase 3 Activity Assay examined caspase 3 activity. Corresponding kits examined oxidative stress levels. BODIPY 581/591 C11 assay evaluated lipid reactive oxygen species. Iron Assay Kit assessed iron content. Western blot tested the expression of apoptosis-, ferroptosis- and Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling-associated proteins. Molecular docking verified the binding of ICS II with Keap1. The existing experimental results unveiled that ICS II elevated the viability whereas reduced the apoptosis, oxidative stress, and ferroptosis in MPP + -treated SK-N-SH cells in a concentration-dependent manner. Furthermore, ICS II declined Keap1 expression while raised Nrf2, heme oxygenase 1, and GPX4 expression. In addition, ICS II had a strong binding with Keap1 and Nrf2 inhibitor ML385 partially abolished the suppressive role of ICS II in MPP + -triggered apoptosis, oxidative stress, and ferroptosis in SK-N-SH cells. To summarize, ICS II might inhibit apoptosis, oxidative stress, and ferroptosis in the MPP + -stimulated PD cell model, which might be due to the activation of Keap1/Nrf2/GPX4 signaling.
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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分子生物学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Qiang-Ming Li,Xiang Li,Shuang-Qiao Su,Yu-Tong Wang,Tong Xu,Xue-Qiang Zha,Li-Hua Pan,Zhen-Zi Shang,Feng-Yun Zhang,Jian-Ping Luo
Background Parkinson's disease (PD) is an age-related neurodegenerative disorder without effective treatments. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been suggested to be capable of protecting against PD by inhibiting endoplasmic reticulum (ER) stress-mediated neuronal apoptosis. Purpose This study was aimed to evaluate the antiparkinsonian effect of dendrobine and reveal its underlying mechanisms from the perspective of MANF-mediated ER stress suppression. Methods Behavioral assessments of PD mice as well as LDH/CCK-8 assay in SH-SY5Y cells and primary midbrain neurons were carried out to detect the antiparkinsonian effect of dendrobine. Immunofluorescence, western blot, flow cytometry and shRNA-mediated MANF knockdown were used to determine the apoptosis of dopaminergic neurons and the expressions of ER stress-related proteins for investigating the underlying mechanism of dendrobine. Results Dendrobine significantly ameliorated the motor performance of PD mice and attenuated the injuries of dopaminergic neurons. Dendrobine could also relieve neuronal apoptosis, up-regulate MANF expression and inhibit ER stress, which were largely abolished by shRNA-mediated MANF knockdown in PD model. Conclusion Dendrobine might protect against PD by inhibiting dopaminergic neuron apoptosis, which was achieved by facilitating MANF-mediated ER stress suppression. Our study suggested that dendrobine could act as a MANF up-regulator to protect against PD, and provided a potential candidate for exploring etiological agents of PD.
研究领域:
神经科学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
NEUROTOXICOLOGY
·
2021
·
IF 4.294
Qingxin Song,Shanxin Peng,Xiaosong Zhu
Baicalein, a major bioactive flavone constituent isolated from Scutellaria baicalensis Georgi, has neuroprotective properties in several neurological disorders. Many studies suggest that oxidative stress plays a central role in the pathogenesis of Parkinson’s disease (PD). Baicalein has also been shown to have antioxidant effects. Therefore, the current study was designed to investigate whether baicalein could protect against MPP + /MPTP-induced neurotoxicity via suppressing oxidative stress in vitro and in vivo . In vitro , our results showed that baicalein increased cell viability in MPP + -treated SH-SY5Y cells. Treatment with baicalein could reversed the increased MDA and ROS levels, and the decreased GSH levels in MPP + -treated SH-SY5Y cells. In MPTP-treated mice, baicalein ameliorated MPTP-induced motor impairment and suppressed the MPTP-induced accumulation of iron and lipid peroxides. Besides, baicalein improved the neurotoxicity induced by MPTP as seen by a significant raise of tyrosine hydroxylase (TH) and simultaneous decrease of monoamine-oxidase-B (MAO-B). The inhibitory effect of baicalein on oxidative stress probably was partially governed by inhibition of ERK activation. In conclusion, our results suggest that baicalein could prevent MPP+/MPTP-induced neurotoxicity via suppressing oxidative stress.
研究领域:
神经科学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2016
·Vol. 3
·期 5
·299-307
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IF 0
Sun Hong-Ji,Wang Yan,Hao Tong,Wang Chang-Yong,Wang Qi-Yu,Jiang Xiao-Xia
Glutathione (GSH) depletion has been an important contributor to the dysfunction of dopamine neurons. Polyamidoamine-GSH (PAMAM-GSH) was synthesized and the delivery effect of GSH into PC12 cells was tested. MTT assessment for cytotoxicity and reactive oxygen species (ROS) as well as nitrite oxide (NO) and intracelluar superoxide dismutase (SOD) detection for antioxidative ability were performed. Furthermore, the antiapoptotic ability was analysed by assessing caspase-3, JNK1/2 and Erk1/2 expression. Our data indicated that PAMAM-GSH is an effective agent to replenish GSH into PC12 cells. PAMAM-GSH developed its antioxidative and protective ability for 1-methyl-4-phenylpyridinium (MPP)-induced PC12 cells by reducing the intracellular levels of ROS and SOD activity as well as decreasing the release of NO. Meanwhile, PAMAM-GSH could inhibit caspase-3 activation and might show its antiapoptotic ability to MPP-induced PC12 cells through JNK2/Erk1/2 pathway. In summary, these studies suggest that PAMAM-GSH conjugate has an intrinsic ability to penetrate PC12 cells and deliver GSH into these cells which may provide a new strategy for clinical applications in the treatment of Parkinson’s disease.
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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疾病模型
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DOI
PubMed
Food & Function
·
2019
·Vol. 10
·期 9
·6009-6019
·
IF 3.241
Yun Yu,Xiu-Yuan Lang,Xi-Xi Li,Run-Ze Gu,Qing-Shan Liu,Rongfeng Lan,Xiao-Yan Qin
The major bioactive ingredient THSG of Polygonum multiflorum is well established for its anti-oxidation, anti-aging and anti-inflammation properties. Increasing evidence supports the capacity of THSG to ameliorate the biochemistry of neurotrophins and their downstream signaling axis in mouse models to attenuate neurodegenerative diseases such as Alzheimer's and Parkinson's disease. In this study, the neuroprotective effects of THSG were studied in vitro and in vivo. In cultured mesencephalic dopamine neurons and SH-SY5Y cell line, it was found that THSG protected the integrity of the cell body and neurite branching from MPP+-induced toxicity by restoring the expression of FGF2 and BDNF and their downstream signaling pathways to inhibit apoptosis and promote cell survival. The inhibition of Akt signaling by LY294002 or TrkB activity by K252a eliminated the neuroprotective effects of THSG. In the MPTP-induced mouse models of Parkinson's disease, THSG ameliorated the animal behaviors against MPTP-induced neurotoxicity, which was demonstrated by the pole test and the tail suspension test. Biochemical and immunohistochemical analysis verified the THSG-mediated restoration of the FGF2-Akt and BDNF-TrkB signaling axis in the substantia nigra and corpus striatum and the recovery of dopaminergic neurons. These results establish the neuroprotective effects of THSG in vitro and in vivo and unravel the underlying mechanism against toxin-induced neural atrophy, providing a new avenue for the use and pharmacological research of edible medicine for anti-neurodegenerative diseases.
研究领域:
神经科学
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药理学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF VINYL & ADDITIVE TECHNOLOGY
·
2026
·
IF 4
Dengwang Lai,Cheng Cao,Wuyan Cao,Li Liu,Yuejun Liu,Jun Yang
Polyamide 6 (PA6) is inherently flammable and prone to severe melt-dripping, which severely restricts its application in aerospace, rail transit, and public safety sectors. To address this, we developed a complementary flame-retardant system by incorporating electrochemically exfoliated graphene (GR), melamine polyphosphate (MPP), and aluminum diethylphosphinate (ADP) into PA6 via in situ polymerization. The thermal stability and interactions among the three components were thoroughly investigated. The results indicate that the optimized formulations exhibit significant flame-retardant enhancement. Specifically, the GR/MPP/ADP/PA6-012 and GR/MPP/ADP/PA6-75 composites achieved limiting oxygen index (LOI) values of 35% and 29%, respectively, and both passed the vertical burning test and achieved V-0 rating, without any dripping. In cone calorimetry, the GR/MPP/ADP/PA6-57 composite demonstrated the most effective heat-release suppression, with the peak heat release rate (pHRR) and total heat release (THR) significantly reduced to 76.3 kW m −2 and 37.7 MJ m −2 , respectively. Mechanistic analysis reveals that GR forms a continuous, compact physical barrier during combustion, effectively hindering heat transfer. MPP promotes the formation of an expanded char layer, enhancing condensed-phase protection. Meanwhile, ADP releases PO · radicals in the gas phase to quench flame-active species and simultaneously promotes char formation. The three components work complementarily, establishing a multi-level “barrier–charring–quenching” flame-retardant network. This study proposes an efficient and environmentally friendly flame-retardant strategy for PA6. By optimizing the ratio of each flame retardant, the resulting composites exhibit superior flame-retardant performance, offering new insights into the flame-retardant modification of engineering plastics and the design of multi-component systems. Highlights GR/MPP/ADP flame-retardant system for PA6 was developed via electrochemistry and in situ polymerization. Electrochemically exfoliated GR forms a continuous two-dimensional physical barrier in PA6 with excellent dispersibility. The ternary system achieves an LOI of 35% and vertical burning test V-0 rating without any dripping. Optimized composite reduced pHRR by 85.3% and THR by 28.5% in cone calorimetry. Synergistic GR/MPP/ADP system builds a barrier–charring–quenching flame-retardant network.
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高影响因子
JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY
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2025
·
IF 3.1
Li Quanyang,Yu Liang,Shen Lv,Fu Jiankun,Zhou Ru,Hao Min,Jiang Juncheng
Polypropylene (PP) is a widely used thermoplastic resin known for its strong properties, including chemical stability, electrical insulation, and high abrasion resistance. However, its low ignition point and rapid burning rate pose significant fire risks, necessitating the incorporation of flame retardants. In this study, cobalt metal–organic framework (Co-MOF), melamine polyphosphate (MPP), and expandable graphite (EG) were combined to enhance the flame retardancy of PP. The optimal blending ratio was determined, and the results showed that PP/MPP/2 mass% Co-MOF/15 mass% EG composites exhibited superior flame retardancy. These composites achieved a critical oxygen index (LOI) of 28%, a V-0 rating in the UL-94 test, and significantly reduced heat release and smoke production during combustion. The synergistic effect of MPP, Co-MOF, and EG facilitated the formation of a dense, thermally stable carbon layer, which effectively hindered flame propagation and improved fire safety. These findings provide valuable insights for the development of flame-retardant PP materials. Graphical abstract
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高影响因子
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
·
2025
·Vol. 29
·期 4
·487
·
IF 2.2
Tingting Yu,Zirui Yuan,Jiaona Yu,Lu Chen,Wei Hao,Xiaohui Xu
Melittin (MEL) is the main bioactive component of bee venom and has been reported to have various pharmacological effects. This study investigates the protective effect of MEL on MPP + -injured HT22 cells and the possible mechanisms involved. We treated the cells with 4 mM MPP + for 24 h to induce a cellular injury model. HT22 cells were pretreated with 0.1 µM MEL for 6 h and then exposed to 4 mM MPP + for 24 h. We measured cell viability, the expression of Bax, the indicators and protein levels associated with apoptosis and parthanatos, and the co-localisation of MEL and mitochondria, and mitochondrial function-related indices such as the mitochondrial membrane potential (MMP) and mito-SOX. We show that PAR protein expression was significantly increased in the MPP + -treated cell model and that the parthanatos inhibitor DPQ significantly reduced MPP + -induced cell death, suggesting that MPP + can cause PARP1-dependent cell death. MEL significantly inhibited cell death, increased cell viability as well as NAD+ and ATP levels, increased the expression of Bcl-2 and suppressed the activation of Bax, cleaved-caspase3, and cleaved-PARP1. Moreover, MEL was found to be localised on the mitochondria of HT22 cells and to improve mitochondrial functions including increased MMP and decreased mitochondrial reactive oxygen species. We speculate that MEL may protect neurons against MPP + -induced HT22 cell injury by inhibiting Bax activation, suppressing changes in mitochondrial permeability, and improving mitochondrial function, thereby preventing cell parthanatos and apoptosis.
研究领域:
神经生物学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
MOLECULAR PLANT PATHOLOGY
·
2020
·Vol. 21
·期 9
·1179-1193
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IF 4.326
Wenqin Lu,Fengyan Deng,Jinbu Jia,Xiaokang Chen,Jinfang Li,Qujiang Wen,Tingting Li,Yuling Meng,Weixing Shan
Phytophthora species are destructive plant pathogens that cause significant crop losses worldwide. To understand plant susceptibility to oomycete pathogens and to explore novel disease resistance strategies, we employed the Arabidopsis thaliana–Phytophthora parasitica model pathosystem and screened for A. thaliana T-DNA insertion mutant lines resistant to P. parasitica . This led to the identification of the resistant mutant 267-31, which carries two T-DNA insertion sites in the promoter region of the ethylene-responsive factor 19 gene ( ERF019 ). Quantitative reverse transcription PCR (RT-qPCR) assays showed that the expression of ERF019 was induced during P. parasitica infection in the wild type, which was suppressed in the 267-31 mutant. Additional erf019 mutants were generated using CRISPR/Cas9 technology and were confirmed to have increased resistance to P. parasitica . In contrast, ERF019 overexpression lines were more susceptible. Transient overexpression assays in Nicotiana benthamiana showed that the nuclear localization of ERF019 is crucial for its susceptible function. RT-qPCR analyses showed that the expression of marker genes for multiple defence pathways was significantly up-regulated in the mutant compared with the wild type during infection. Flg22-induced hydrogen peroxide accumulation and reactive oxygen species burst were impaired in ERF019 overexpression lines, and flg22-induced MAPK activation was enhanced in erf019 mutants. Moreover, transient overexpression of ERF019 strongly suppressed INF-triggered cell death in N. benthamiana . These results reveal the importance of ERF019 in mediating plant susceptibility to P. parasitica through suppression of pathogen-associated molecular pattern-triggered immunity.
研究领域:
植物病理学
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分子生物学
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遗传学
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DOI
PubMed
高影响因子
MOLECULAR PLANT PATHOLOGY
·
2025
·Vol. 26
·期 12
·e70196
·
IF 4.9
Liwen Ding,Zewen Liu,Weihang Wang,Yang Yang,Ren Sa,Hongmei Wang,Liru Mi,Yalan Qin,Shaocong Kang,Meruyert Medelbek,Assiya Ansabayeva,Yuling Meng,Weixing Shan
Negative immune regulator CAD7 is a non-canonical member of the CAD (cinnamyl alcohol dehydrogenase) family in plants. However, little is known on its biochemical functions and underlying mechanisms of immune regulation. Here, we show that Arabidopsis thaliana AtCAD7 harbours substrate-binding residues divergent from lignin-forming CADs (AtCAD4/5), being conserved with bacterial alcohol dehydrogenases EcYahK and EcYjgB. Comparative enzymatic analysis revealed that AtCAD7 exhibits a broad substrate preference for diverse small-molecule aldehydes, including histamine-derived intermediates, being distinct from the canonical lignin-forming AtCAD5. Metabolomic analyses revealed that AtCAD7 -overexpression transformants were affected in the biosynthesis and metabolism of amino acids, whereas AtCAD7 -silencing lines were activated in the phenylpropanoid pathway and increased in flavonoid accumulation. Histamine was elevated in AtCAD7 -overexpression lines and functional validation revealed its promoted effect on plant susceptibility to Phytophthora parasitica . In contrast, phytoalexins scopolin and chlorogenic acid were enriched in AtCAD7 -silencing lines, accompanied by upregulated expression of phenylpropanoid pathway-related genes. Functional validation demonstrated that scopolin and chlorogenic acid enhanced plant resistance to P. parasitica . Collectively, our study uncovers that CAD7 functions as a metabolic hub linking small-molecule aldehyde reductase activity to immune suppression, providing a potential novel target for developing crops with enhanced resistance to Phytophthora pathogens.
研究领域:
植物生物学
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生物化学
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分子遗传学
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植物-病原体互作
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代谢组学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PLANT PATHOLOGY
·
2021
·Vol. 23
·期 1
·60-77
·
IF 5.663
Changyun Liu,Shaorui Tian,Xing Lv,Yundan Pu,Haoran Peng,Guangjin Fan,Xiaozhou Ma,Lisong Ma,Xianchao Sun
Asparagine synthetase is a key enzyme that catalyses the conversion of amide groups from glutamine or ammonium to aspartate, which leads to the generation of asparagine. However, the role of asparagine synthetase in plant immunity remains largely unknown. Here, we identified a Nicotiana benthamiana asparagine synthetase B (NbAS-B) that associates with tomato mosaic virus coat protein-interacting protein L (IP-L) using the yeast two-hybrid assay and examined its role in tobacco mosaic virus (TMV) resistance. The association of IP-L with NbAS-B was further confirmed by in vivo co-immunoprecipitation, luciferase complementation imaging, and bimolecular fluorescence complementation assays. IP-L and NbAS-B interact in the nucleus and cytosol and IP-L apparently stabilizes NbAS-B, thus enhancing its accumulation. The expressions of IP-L and NbAS-B are continuously induced on TMV-green fluorescent protein (GFP) infection. Co-silencing of IP-L and NbAS-B facilitates TMV-GFP infection. Overexpression of NbAS-B in tobacco reduces TMV-GFP infection by significantly improving the synthesis of asparagine. Furthermore, the external application of asparagine significantly inhibits the infection of TMV-GFP by activating the salicylic acid signalling pathway. These findings hold the potential for the future application of asparagine in the control of TMV.
研究领域:
植物病理学
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分子生物学
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植物科学
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DOI
PubMed
高影响因子
MOLECULAR PLANT PATHOLOGY
·
2026
·Vol. 27
·期 5
·e70265
·
IF 5
Yarui Yang,Jikai Yu,Jinxi Yang,Yulin Wang,Wenrui Hou,Dongfang Zhang,Jianquan Wang,Wenfeng Nie,Yan Zhang,Xiaoyun Wang,Xiuming Li,Qinghua Shi
Bacterial speck of tomato, caused by Pseudomonas syringae pv. tomato (Pst), is a globally significant disease leading to substantial yield losses. This study demonstrated that methyl caffeate (MC), a plant-derived phenolic acid, exhibited dual functionality against Pst strain DC3000 through direct antibacterial action and indirect host resistance priming. In vitro assays revealed MC's potent inhibitory activity against bacterial growth, characterised by disruption of membrane integrity, leading to intracellular content leakage and reactive oxygen species (ROS) accumulation. Transcriptomic analysis identified 434 upregulated and 326 downregulated genes, with differentially expressed genes primarily enriched in pathways related to flagellar assembly, motility, quorum sensing, chemotaxis and the type III secretion system (T3SS), thereby impairing bacterial motility and virulence. Concurrently, MC enhances plant defence responses by inducing the transcriptional expression of defence hormone signalling pathway-related genes and increasing the activities of defence enzymes such as phenylalanine ammonia-lyase (PAL) and polyphenol oxidase (PPO). This modulation helps maintain ROS homeostasis and alleviates oxidative damage caused by Pst infection, thereby attenuating disease progression. These findings established MC as a multifunctional agent combining direct bactericidal effects with plant immunity induction, providing a sustainable strategy for bacterial speck management.
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PubMed
高影响因子
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