Developmental Neurobiology
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2025
·Vol. 85
·期 2
·e22961
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IF 2.3
Yongzhi San,Minghua Wang
Background Mitophagy is important for normal neural activity. Epilepsy is intimately linked to neurotoxicity due to mitochondrial dysfunction. Cordycepin (Cor) has been shown to exert neuroprotective effects. This study aims to investigate whether Cor could mitigate neurotoxicity in epilepsy by modulating mitophagy. Methods In vitro, kainic acid (KA) was utilized to induce cytotoxicity in HT22 cell. Cell viability was assessed using the CCK-8 assay, while cell damage was evaluated through an LDH kit. Flow cytometry was used to assess apoptosis. The expressions of G protein-coupled receptor 120 (GPR120), apoptosis, and mitophagy-related proteins were analyzed by western blot. Inflammatory factors and oxidative stress levels were examined by kits. DCFH-DA staining was applied to observe cellular reactive oxygen species (ROS) levels. The three-dimensional coordinates of GPR120 were retrieved from the PDB database, and molecular docking was performed using AutoDock. Immunofluorescence staining was used to observe mitophagy level. Results Cor significantly attenuated KA-induced HT22 cell viability injury and inflammation, while suppressing ROS and oxidative stress levels. Notably, Cor ameliorated the decrease of mitophagy level observed in HT22 cells treated with KA. GPR120 expression was upregulated following KA treatment and further elevated after adding Cor. Cor could bind to GPR120. Interference with GPR120 reversed the ameliorative effects of Cor on KA-induced mitophagy and cytotoxicity in HT22 cells. Conclusion Overall, Cor significantly alleviated KA-induced HT22 cell neurotoxic damage and oxidative stress. This protective effect may be mediated through GPR120-regulated mitophagy.
研究领域:
神经科学
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药理学
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PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2025
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IF 2.2
Ying He,Meng-Hui He,Tingting Jin,Siju-Li,Hua-Qiao Wang,Feng He
Tangeretin, a flavonoid from Citri Reticulatae Pericarpium, is known for its neuroprotective effects, but the mechanisms are not fully understood. Alzheimer's disease, a leading neurodegenerative disorder, characterized by amyloid-beta (Aβ) accumulation, represents a significant therapeutic challenge. This study investigates the protective effects of tangeretin against Aβ1-42-induced neurotoxicity using HT22 cells and zebrafish larvae as experimental models. Tangeretin mitigated Aβ 1-42 -induced cytotoxicity, as evidenced by enhanced cell viability and reduced apoptosis. Tangeretin treatment mitigated Aβ 1-42 -induced cytotoxicity in HT22 cells, as evidenced by enhanced cell viability and reduced apoptosis. Mechanistically, tangeretin ameliorated mitochondrial dysfunction by reducing mitochondrial fragmentation, decreasing donut-shaped mitochondria, restoring mitochondrial membrane potential, and attenuating reactive oxygen species (ROS) production. Moreover, tangeretin modulated mitochondria-lysosome interactions by promoting mitophagy and normalizing the prolonged mitochondria-lysosome contact induced by Aβ 1-42 . In zebrafish larvae, Aβ 1-42 exposure resulted in developmental malformations, including pericardial and yolk sac edema, elevated ROS levels, increased apoptosis, and impaired neurodevelopment. Tangeretin effectively counteracted these deficits, as revealed by live imaging, supporting its neuroprotective role observed in cellular models. Collectively, our study suggests that tangeretin may serve as a promising protective agent against Aβ 1-42 -induced neurotoxicity.
研究领域:
神经科学
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细胞生物学
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药理学
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PubMed
高影响因子
Food & Function
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2025
·
IF 5.4
Jingyu Li,Bing Fang,Yao Wu,Yuhang Sun,Yue Liu,haina gao,Ming Zhang
Egg yolk phospholipids are primarily composed of various fatty acids, lysophosphatidylcholine and lysophosphatidylethanolamine. Existing studies demonstrated the neuroprotective activity of egg yolk phospholipids, however, which products of these compounds after digestion executive the function have not been clarified. The objective of this study was to investigate the neuroprotective effects of different structural components in egg yolk phospholipids based on a DMNQ-induced oxidative damage in HT22 cells. The findings demonstrate that pre-treatment with diverse egg yolk phospholipid components, particularly the polyunsaturated fatty acids, markedly elevated cell viability, superoxide dismutase activity, diminished ROS generation, reduced malondialdehyde levels and elevated mitochondrial membrane potential. Furthermore, RNA-Seq analysis demonstrated that unsaturated fatty acids exert its neuroprotective effects by upregulating genes involved in cell proliferation (JAG2, YPEL3), nervous system development (NTF5), DNA damage repair (H2AX), and other related processes. These findings provide a theoretical basis for future studies on the characteristic structure of egg yolk phospholipids with profound neuroprotective effects.
研究领域:
营养学
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分子生物学
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神经科学
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PubMed
高影响因子
Phytochemistry Letters
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2023
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IF 1.7
Yu-Chen Chen,Qiong Zheng,Hui Lu,Yi-Xin Zhuang,Ting-Ting Gong,Lie-Feng Ma,Zha-Jun Zhan
A new flavonoid glycoside bearing an unusual furan ring, epimedokoreanin F ( 1 ), was isolated from Epimedium brevicornu , along with 17 known flavonoids ( 2−18 ). The structures of these flavonoids were identified based on interpretation of spectroscopic data and comparison with literature data. Biologically, compounds 1−4 exhibited significant neuroprotective effects on the model of RSL3-induced ferroptosis in HT22 cells. Among them, compound 1 displayed the best activity with EC 50 values of 0.95 μ M, and can be used as lead compound for the development of neuroprotective agent to treat neurological diseases .
研究领域:
药理学
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神经科学
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生物化学
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植物化学
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DOI
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2024
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IF 6
Zheren Tong,Xiaolu Jie,Ziwei Chen,Mingtao Deng,Xin Li,Zhiwen Zhang,Faxiang Pu,Zhangfu Xie,Zijin Xu,Ping Wang
Crocetin (CCT), a natural bioactive compound extracted and purified from the traditional Chinese medicinal herb saffron, has been shown to play a role in neurodegenerative diseases , particularly depression. However, due to challenges with solubility, targeting, and bioavailability, formulation development and clinical use of CCT are severely limited. In this study, we used the emulsification-reverse volatilization method to prepare CCT-loaded nanoliposomes (CN). We further developed a borneol (Bor) and lactoferrin (Lf) dual-modified CCT-loaded nanoliposome (BLCN) for brain-targeted delivery of CCT. The results of transmission electron microscope (TEM) and particle size analysis indicated that the size of BLCN (∼140 nm) was suitable for transcellular transport across olfactory axons (∼200 nm), potentially paving a direct path to the brain. Studies on lipid solubility, micropolarity, and hydrophobicity showed that BLCN had a relatively high Lf grafting rate (81.11 ± 1.33 %) and CCT entrapment efficiency (83.60 ± 1.04 %) compared to other liposomes , likely due to Bor improving the lipid solubility of Lf, and the combination promoting the orderly arrangement of liposome membrane molecules. Microplate reader and fluorescence microscopy analysis showed that BLCN efficiently promoted the endocytosis of fluorescent coumarin 6 into HT22 cells with a maximal fluorescence intensity of (13.48 ± 0.80 %), which was significantly higher than that of CCT (5.73 ± 1.17 %) and CN (12.13 ± 1.01 %). BLCN also exhibited sustained function, remaining effective for more than 12 h after reaching a peak at 1 h in cells, while CN showed a significant decrease after 4 h. The uptake mechanisms of BLCN in HT22 cells mainly involve energy-dependent, caveolae-mediated, and microtubule-mediated endocytosis, as well as micropinocytosis. Furthermore, BLCN displayed a significant neuroprotective effect on HT22 cells in glutamate-, corticosterone-, and H 2 O 2 -induced models. Tissue fluorescence image analysis of mice showed that BLCN exhibited substantial retention of fluorescent DiR in the brain after nasal administration for 12 h. These findings suggest that CCT has the potential for cellular uptake, neuroprotection , and targeted delivery to the brain following intranasal administration when encapsulated in Bor and Lf dual-modified nanoliposomes.
研究领域:
药学
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神经科学
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药物递送系统
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生物技术
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DOI
PubMed
高影响因子
Food Bioscience
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2024
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IF 4.8
Jiayu Zheng,Fengjiao Fan,Wenqian Tang,Nanlong Li,Xiaoyi Jiang,Yong Fang
The TSeMMM and SeMDPGQQ, two selenium-containing peptides derived from Se-enriched rice protein hydrolysates, have previously been demonstrated to show neuroprotective properties against high-dose lead exposure. However, the potential toxicological effects of these functional peptides on low-dose lead-induced neurotoxicity remain poorly understood. The present study aimed to investigate the protective mechanism of two selenium-containing peptides in mitigating low-dose Pb 2+ -induced damage in HT22 cells. Results showed that treatment with 40 μmol/L Pb 2+ significantly reduced cell viability and increased apoptosis, both of which were alleviated by 40 μmol/L TSeMMM and SeMDPGQQ treatment. Furthermore, two peptides exhibited antioxidant potentials by reducing reactive oxygen species levels to 32.19% and 79.29% of the model group, respectively. They also enhanced antioxidant enzyme activities and mitigated oxidative stress through activation of the Keap1/Nrf2 pathway. Additionally, two peptides improved mitochondrial function by elevating mitochondrial membrane potential, ATP production while dramatically reducing reactive oxygen species levels. Interestingly, TSeMMM exhibited superior neurointerventional effects compared to SeMDPGQQ. The RNA sequencing analysis revealed that TSeMMM modulated gene expressions related to oxidative stress and neuroprotective function. The study provides insights into the protective mechanism underlying selenium-containing peptides for mitigating neuronal damage.
研究领域:
神经毒理学
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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
高影响因子
Bioengineered
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2021
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IF 3.269
Jianan Li,Haoran Bi
Cypermethrin (CMN) is a widely used artificial synthetic pesticide that causes neurotoxicity in the hippocampus. However, the underlying toxicological targets and mechanisms remain unclear. In this study, network pharmacology analysis and in vitro models were integrated to investigate the effect and mechanism of CMN-induced hippocampal neurotoxicity. A total of 88 targets of CMN-induced hippocampal neurotoxicity were predicted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment (KEGG) analyses suggested that these targets were related to multiple GO terms and signaling pathways. To further investigate underlying mechanism, the top 10 hub targets (Akt1, Tnf, Ptgs2, Casp3, Igf1, Sirt1, Jun, Cat, Il10, and Bcl2l1) were screened. Furthermore, cell viability and lactate dehydrogenase (LDH) assays demonstrated that CMN was toxic to HT22 cells in a time- and dose-dependent manner. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining revealed that treatment with CMN increased the proportion of apoptotic cells. In addition, the real-time quantitative polymerase chain reaction (RT-qPCR) results indicated that CMN altered the mRNA expression levels of most of the hub targets, with the exceptions of Igf1 and Jun. The results demonstrated that multiple targets and signaling pathways were involved in CMN-induced hippocampal neurotoxicity. These findings provided reference values for subsequent studies of the toxicological mechanism of CMN.
研究领域:
毒理学
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神经科学
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药理学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2022
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IF 5.195
Xiaohui Jin,Leilei Zhu,Shuaifei Lu,Caiyin Li,Ming Bai,Erping Xu,Jiduo Shen,Yucheng Li
Mitochondrial dysfunction has been reported to be involved in the pathogenesis of depression, and mitophagy is a key pathway for mitochondrial quality control. This study aimed to investigate the effect of baicalin on mitophagy in the hippocampus of mice exposed to chronic unpredictable mild stress (CUMS) and explore its potential mechanism. After exposure to CUMS for 6 weeks, mice were given baicalin (20 mg/kg) or fluoxetine (20 mg/kg) by oral gavage for 4 weeks, and HT22 cells were injured by corticosterone (CORT) in vitro. Depression-like behaviors were assessed by sucrose preference test and tail suspension test . The mitochondrial structure was observed by transmission electron microscopy . Detection of mitophagy and mitophagy-related protein by mitophagy kit and Western blot . The results showed that baicalin improved depressive-like behaviors in CUMS mice, and ameliorated mitochondrial structural impairment in the hippocampus neuron. Baicalin significantly down-regulated light chain 3(LC3)II/I, protein sequestosome 1 (P62), and translocase of the outer membrane 20 (TOM20), and up-regulated Nip-like protein (NIX), Adenylate activated protein kinase (AMPK), and Peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α. Furthermore, molecular docking showed that baicalin interacts with AMPK through hydrogen bonding. Baicalin increased NIX and AMPK, and improved mitophagy level and mitochondrial function in HT22 cells. Treatment with Phorbol 12-Myristate 13-acetate demonstrated that up-regulation of NIX ameliorated CORT-induced mitochondrial dysfunction in HT22 cells. In conclusion, the present study suggested that the antidepressant effect of baicalin may be related to the enhancement of NIX-mediated mitophagy through activating the AMPK/PGC-1α pathway by directly binding to AMPK.
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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PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2024
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IF 4.2
Yuan Liu,Xiaohui Jin,Caiyin Li,Jingjing Bu,Baoying Wang,Ming Bai,Pan Su,Erping Xu,Yucheng Li
Defective mitophagy is closely related to the neuronal dysfunction and major depressive disorder (MDD). Our previous study found that baicalin could enhance nip-like protein (NIX)-mediated mitophagy and exhibit antidepressant effects, and predicted that AMPK may be the pharmacological target of baicalin. However, validated experiments are lacking. In the present study, we first demonstrated the effect of baicalin on hippocampal NIX-mediated mitophagy in CORT-induced depressive mice. Secondly, we transfected siRNA to knockdown AMPK, PGC-1α, and NIX respectively in HT22 cells, and detected the effects of baicalin on mitochondrial function, AMPK/PGC-1α/NIX pathway protein expression and mitophagy levels. Finally, AAV-shAMPKα was injected into hippocampal CA3 to knockdown AMPK in mice to validate the antidepressant effects of baicalin in vivo. The results showed that CORT induced depressive-like behaviors, accompanied with neuronal damage, mitochondrial injury, and inhibited mitophagy in the hippocampus, which were prevented by baicalin (20 mg/kg) treatment. In HT22 cells, baicalin remarkably ameliorated mitochondrial dysfunction and mitophagy disturbance induced by CORT, and these protective effects of baicalin were blocked by knockdown of AMPK, PGC-1α and NIX. Moreover, the beneficial effects of baicalin on depressive-like behaviors and NIX-mediated mitophagy were suppressed by knockdown of AMPKα in mice. Our present results further demonstrated that baicalin promotes NIX-mediated mitophagy and improves depression in an AMPK-dependent manner.
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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抑郁症
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PubMed
高影响因子
Antioxidants
·
2024
·Vol. 13
·期 11
·1296
·
IF 6
Yue Liu,Chunhong Chen,Zhihui Hao,Jianzhong Shen,Shusheng Tang,Chongshan Dai
Exposure to cadmium sulfate (CdSO4) can lead to neurotoxicity. Nevertheless, the precise molecular mechanisms underlying this phenomenon remain unclear, and effective treatment strategies are scarce. This study explored the protective effects of ellagic acid (EA), a natural polyphenolic compound, against CdSO4exposure-induced neurotoxicity in HT22 cells and the underlying molecular mechanisms. Our findings demonstrated that exposure of HT22 cells to CdSO4resulted in apoptosis, which was effectively reversed by EA in a dose-dependent manner. EA supplementation also decreased reactive oxygen species (ROS) and mitochondrial ROS production, reduced malondialdehyde (MDA) levels, and restored the activities of superoxide dismutase (SOD) and catalase (CAT). Additionally, EA supplementation at 5–20 μM significantly counteracted Cd-induced the loss of mitochondrial membrane potential and the decrease of ATP and reduced the ratio of Bax/Bcl-2 and cleaved-caspase-3 protein expression. Furthermore, EA supplementation resulted in the upregulation of Nrf2 and HO-1 protein and mRNAs while simultaneously downregulating the phosphorylation of JNK and p38 proteins. The pharmacological inhibition of c-Jun N-terminal kinase (JNK) partially attenuated the activation of the Nrf2/HO-1 pathway induced by CdSO4and exacerbated its cytotoxic effects. In conclusion, our findings suggest that ethyl acetate (EA) supplementation offers protective effects against CdSO4-induced apoptosis in HT22 cells by inhibiting oxidative stress and activating the Nrf2 signaling pathway. Furthermore, the activation of the JNK pathway appears to play a protective role in CdSO4-induced apoptosis in HT22 cells.
研究领域:
毒理学
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药理学
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细胞生物学
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神经科学
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DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2022
·
IF 3.322
Ting Zhou,Bao Yang
Prenylated resveratrols are drug candidates presented in many natural sources. They possess multiple pharmacological activities. Due to the limited abundance in nature and disadvantage of chemical synthesis, it is required to produce prenylated resveratrols by biological strategy. In this work, a prenyltransferase iacE from Pestalotiopsis fici was prepared by heterologous overexpression. It could catalyze 2- C -prenylation of resveratrol efficiently. Dimethylallyl diphosphate (DMAPP) and geranyl diphosphate (GPP) could serve as prenyl donor. Glu97, Thr114 and Tyr413 were proved to be important residues in the active site by site-directed mutagenesis. The product was purified and identified to be 2- C -prenyl resveratrol by NMR . 2- C -prenyl resveratrol exerted neuroprotective activity through inhibiting ROS overproduction and improving the activities of antioxidant enzymes in HT22 cell. The genes involved in antioxidant defense were regulated, including upregulated CAT , SOD2 , NFE2L2 , GPx4 , and downregulated PTGS2 and ACSL4 . These results supplied a novel technique for prenylated resveratrols production.
研究领域:
生物技术
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药理学
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神经科学
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DOI
PubMed
高影响因子
FITOTERAPIA
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2022
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IF 3.204
Meixi He,Yingang Feng,Yi Wang,Mengchun Cheng,Xiaozhe Zhang,Lihua Zhang
Cysteine-rich peptides (CRPs) are stable molecules that contain multiple disulphide bonds . Various CRPs are found in plants and animals, representing potential compounds for drug development with diverse activities. Modification of CRPs, such as glycation, has attracted increased attention due to its special structural and functional properties. Hence, this study explored a CRP isolated from the Chinese herb Achyranthes bidentata Blume, which contains a glycation modification. Herein, a reverse phase high-performance liquid chromatography system with mobile phases was used to extract and purify the peptide. The eluted peptide was detected using high resolution mass spectrometry and structurally identified using high resolution mass spectrometry and nuclear magnetic resonance. The effect of the peptide on the viability of N -methyl-D-aspartic acid (NMDA)-induced HT22 cells was determined using a cell assay. Here, a new cysteine-rich glycation peptide, termed glycation-bidentatide (Gly-BTP), with three pairs of disulphide bonds and a glycation modification at the N-terminus linked to cysteine, was discovered. Cell bioactivity assay results suggested that Gly-BTP might be a potential therapeutic and provide a neuroprotective effect in NMDA-induced HT22 murine hippocampal neuronal cells. The discovery of Gly-BTP will promote the understanding of the role of CRPs in neuroprotection .
研究领域:
药理学
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生物化学
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神经科学
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植物化学
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产品关联
DOI
PubMed
高影响因子
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