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Phytochemistry Letters · 2019 · IF 1.338

Four new tirucallane-type triterpenoids from Sapindus mukorossi Gaertn. flowers induced neurite outgrowth in PC12 cells related to insulin-like growth factor 1 receptor/phosphoinositide 3-kinase/extracellular regulated protein kinase signaling pathway

Yanhui Wang,Xueli Cao,Boyu Qin,Ying Wang,Lan Xiang,Jianhua Qi

Four new tirucallane-type saponins (i.e., sapinmusaponin S–V, which include one new structure and three new stereoisomers) and a known compound sapinmusaponin G were isolated from the flowers of Sapindus mukorossi . All of them could significantly induce neurite outgrowth of PC12 cells. The structures of active compounds were determined using spectroscopic data and chemical derivatization. Specific inhibitor experiments and Western blot analysis of sapinmusaponin S, which is the most active compound, were performed. Results indicated that the insulin-like growth factor 1 receptor/phosphoinositide 3-kinase/extracellular regulated protein kinase signaling pathway is involved in this action.

CAS / MDL: 50-99-7
研究领域: 药理学 · 植物化学 · 神经科学
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ADVANCED MATERIALS · 2025 · IF 26.8

Visible Periodic Piezoelectric Domains in Silk Fibroin for Neurite-Orientated Extension

Jie Chen,Chenjing Zhang,Renwei Liu,Longyang Jia,Qianqian Niu,Suna Fan,Yaopeng Zhang

The development of visible periodic piezoelectric domains is highly attractive but challenging to overcome the homogeneous distribution and lack of visualization of the electric field on traditional piezopolymers. This work reports an in situ synthesis to create customized silver patterns with micron-level distinguishability. This method serves to form visible periodic piezoelectric domains and endows the silk fibroin (SF) piezoelectric generator with maximum root mean square current, energy density, and voltage of 5.1 mA, 6.7 W m −2 and 529.5 mV, respectively, under an ultrasound intensity of 1.0 W cm −2 . The oriented piezoelectric electric field is periodically distributed into the SF film with ultrasound-driven assistance and remarkably regulates neurite directional growth, length, and gene expression. Additionally, these piezoelectric domains enable the direct and timely observation of the electric field's effect on neurites by biological microscopy. This approach paves the way for great potential in tailored electric stimulation for cell biology and medical engineering.

CAS / MDL: 10102-17-7
研究领域: 生物医学工程 · 材料科学 · 细胞生物学
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BIOMACROMOLECULES · 2025 · IF 5.4

Multifunctions of Sustainable Chondroitin Sulfates with Predominant Subtypes and Low Molecular Weights on Neurite Outgrowth

Shuqin Xu,Meiling Qiu,Liyuan Liang,Yue Chen,Yajia Wang,Jing Wu,Jinghua Chen

Three chondroitin sulfate (CS) analogues with predominant subtypes (A, C, and E) were prepared from engineered Escherichia coli K4 combined with regioselective sulfation. CS with the designed sulfates as the main components was characterized by nuclear magnetic resonance spectroscopy, elementary analysis, and disaccharide analysis. CS prepared from the native or degraded capsular polysaccharide had molecular weights of 1.55 × 104–1.90 × 104 and 5.6 × 103–7.4 × 103, respectively. We found that CS with dual sulfates promoted the outgrowth and survival of hippocampal neurons, whereas CS with monosulfate had an inhibitory effect. CS interacted with the nerve growth factor (NGF) and tyrosine kinase (TrkA), which activated the extracellular signal-regulated kinase (ERK) signaling pathway to modulate the outgrowth of hippocampal neurons. This work clarified the multiple effects of CS on neurite outgrowth based on nonanimal-sourced glycosaminoglycans, which would benefit efforts in discovering their novel functions and therapeutic applications.

研究领域: 生物化学 · 神经科学 · 分子生物学
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BRAIN RESEARCH BULLETIN · 2020 · IF 3.37

Fluoxetine exposure for more than 2 days decreases the neuronal plasticity mediated by CRMP2 in differentiated PC12 cells

Zuotian Wu,Gaohua Wang,Huiling Wang,Ling Xiao,Yanyan Wei,Can Yang

Background Recent studies indicate that antidepressants treatment restores neuronal plasticity. In contrast, some researchers claim that serotonergic antidepressants, including fluoxetine (FLU), may exacerbate neuronal plasticity, which is contradictory and rarely studied. Since almost those studies exposed cells with drugs for 1–2 days as treatment models of antidepressants, it is possible that FLU exposure for longer periods would have opposite effects on neuronal plasticity. Results In the present study, we examined the effects of FLU exposure (up to 3 days) on the neuronal plasticity in differentiated PC12 cells. The cell viability shown a slight decrease at day 2 (93.5 ± 3.5 %), followed by a highly significant decrease at day 3(71.4 ± 4.4 %). As previously reported, neuronal plasticity was significantly upregulated by FLU exposure at day 1. However, the neurite length, activity-regulated cytoskeleton-associated protein (Arc) and c-Fos mRNA were inhibited with FLU exposure at day 3. Similarly, the expression of tubulin, which play important roles in the neuronal plasticity, was the same result. Furthermore, we found α-tubulin interacted with collapsing response mediator protein 2(CRMP2), which is related to neuronal plasticity, and the regulation of CRMP2 activity influenced the neurite length, Arc, c-Fos and tubulin expression. Conclusions The results demonstrated that neuronal plasticity was increased by FLU exposure at day 1, but exposure with FLU for more than 2 days had opposite effect on it. The reduction in neuronal plasticity with FLU exposure for more than 2 days might be involved in some aspects of the therapeutic effect of antidepressant on depression.

研究领域: 神经科学 · 药理学
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Food & Function · 2017 ·Vol. 8 ·期 10 ·3688-3695 · IF 3.247

Bioactivity-guided isolation of neuritogenic triterpenoids from the leaves of Ilex latifolia Thunb

Xueli Cao,Yu Liu,Jing Li,Lan Xiang,Hiroyuki Osada,Jianhua Qi

Ilex latifolia Thunb is a traditional Chinese tea and herbal medicine. In this study, one new triterpene saponin (1) and six known triterpenoids (2–7) were isolated from the methanol extract of I. latifolia using a PC12 cell bioassay system. The structures and stereochemistry of these compounds were elucidated using spectroscopic methods and chemical derivatization. This new triterpene saponin (1) was characterized as an ursolic type acid with a 19α-hydroxyl and a trisaccharide moiety at C-3. Compound 1 significantly promoted the neurite outgrowth in PC12 cells by 52% at 10 μM, whereas compounds 2–7 showed less neuritogenic activity. Structure activity relationship studies indicated that introducing a trisaccharide moiety at C-3 is important for the neuritogenic activity, but the sugar group at C-28 decreased this activity. In addition, compound 1 increased the neurite outgrowth length in primary cortical neuron cells of mice and also exhibited a neuronal protection effect on H2O2-damaged PC12 cells at optimum concentrations.

CAS / MDL: 50-99-7
研究领域: 药理学 · 植物化学 · 神经科学
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Biointerphases · 2019 ·Vol. 14 ·期 6 · IF 2.009

Biofunctionalized silk fibroin nanofibers for directional and long neurite outgrowth

Li Xiufang,Zhang Qiang,Luo Zuwei,Yan Shuqin,You Renchuan

Engineered scaffolds simultaneously exhibiting multiple cues are highly desirable for neural tissue regeneration. Silk fibroin is a promising natural protein material for nerve repair. However, the lack of specific bioactive cues significantly hinders its application. In this study, the electrospun silk fibroin nanofibers with both biochemical and topographical cues were prepared. The alignment of electrospun nanofibers was optimized by controlling the surface linear velocity of a rotating drum. The silk fibroin nanofibers were further functionalized with laminin through covalent binding, confirmed by immunostaining observation. Cell proliferation and neurite outgrowth assays confirmed that the functionalized aligned nanofibers significantly enhanced directional axonal extensions, providing physical and bioactive cues for neurite outgrowth. Furthermore, the tubular scaffolds with longitudinally aligned microchannels were designed by rolling the functionalized silk fibroin nanofibers. The neurite extension across the lumen of the conduit along the direction of the aligned fibers is apparent. These results highlight the ability of laminin-immobilized silk fibroin nanofibers to enhance neurite outgrowth and to control directional neurite extension, providing a useful approach to construct a regenerative microenvironment for nerve repair materials.

CAS / MDL: 920-66-1
研究领域: 生物材料学 · 神经再生医学 · 组织工程学
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ACS Nano · 2024 · IF 15.8

Ionic Potential Relaxation Effect in a Hydrogel Enabling Synapse-Like Information Processing

Li Wang,Song Wang,Guoheng Xu,Youzhi Qu,Hongjie Zhang,Wenchao Liu,Jiqing Dai,Ting Wang,Zhiyuan Liu,Quanying Liu,Kai Xiao

The next-generation brain-like intelligence based on neuromorphic architectures emphasizes learning the ionic language of the brain, aiming for efficient brain-like computation and seamless human-computer interaction. Ionic neuromorphic devices, with ions serving as information carriers, provide possibilities to achieve this goal. Soft and biocompatible ionic conductive hydrogels are an ideal substrate for constructing ionic neuromorphic devices, but it remains a challenge to modulate the ion transport behavior in hydrogels to mimic neuroelectric signals. Here, we describe an ionic potential relaxation effect in a hydrogel device prepared by sandwiching a layer of polycationic hydrogel (CH) between two layers of neutral hydrogel (NH), allowing this device to simulate various electrical signal patterns observed in biological synapses, including short- and long-term plasticity patterns. Theoretical and experimental results show that the selective permeation and hysteretic diffusion of ions caused by the anion selectivity of the CH layer are responsible for potential relaxation. Such an effect allows us with hydrogels to enable synapse-like information processing functions, including tactile perception, learning, memory, and neuromorphic computing. Additionally, the hydrogel device can operate stably even under 180° bending and 50% tensile strain, expanding the pathway for implementing advanced brain-like intelligent systems.

研究领域: 生物医学工程 · 材料科学 · 神经科学
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FASEB JOURNAL · 2019 ·Vol. 33 ·期 5 ·6311-6326 · IF 5.391

Talin promotes integrin activation accompanied by generation of tension in talin and an increase in osmotic pressure in neurite outgrowth

Yifan Wang,Xiaolong Zhang,Jilai Tian,Jinjun Shan,Yunfeng Hu,Yiqian Zhai,Jun Guo

Neuronal polarization depends on the interaction of intracellular chemical and mechanical activities in which the cytoplasmic protein, talin, plays a pivotal role during neurite growth. To better understand the mechanism underlying talin function in neuronal polarization, we overexpressed several truncated forms of talin and found that the presence of the rod domain within the overexpressed talin is required for its positive effect on neurite elongation because the neurite number only increased when the talin head region was overexpressed. The tension in the talin rod was recognized using a Förster resonance energy transfer-based tension probe. Nerve growth factor treatment resulted in inward tension of talin elicited by microfilament force and outward osmotic pressure. By contrast, the glial scar-inhibitor aggrecan weakened these forces, suggesting that interactions between inward pull forces in the talin rod and outward osmotic pressure participate in neuronal polarization. Integrin activation is also involved in up-regulation of talin tension and osmotic pressure. Aggrecan stimuli resulted in up-regulation of docking protein 1 (DOK1), leading to the down-regulation of integrin activity and attenuation of the intracellular mechanical force. Our study suggests interactions between the intracellular inward tension in talin and the outward osmotic pressure as the effective channel for promoting neurite outgrowth, which can be up-regulated by integrin activation and down-regulated by DOK1.—Wang, Y., Zhang, X., Tian, J., Shan, J., Hu, Y., Zhai, Y., Guo, J. Talin promotes integrin activation accompanied by generation of tension in talin and an increase in osmotic pressure in neurite outgrowth. FASEB J. 33, 6311–6326 (2019). www.fasebj.org

研究领域: 神经科学 · 细胞生物学 · 分子生物学
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Frontiers in Bioengineering and Biotechnology · 2022 · IF 6.064

Ti3C2Tx MXene-Coated Electrospun PCL Conduits for Enhancing Neurite Regeneration and Angiogenesis

Li-Ping Nan,Zeng Lin,Feng Wang,Xue-Han Jin,Jia-Qi Fang,Bo Xu,Shu-Hao Liu,Fan Zhang,Zhong Wu,Zi-Fei Zhou,Feng Chen,Wen-Tao Cao,Jian-Guang Wang,Jun-Jian Liu

An electrical signal is the key basis of normal physiological function of the nerve, and the stimulation of the electric signal also plays a very special role in the repair process of nerve injury. Electric stimulation is shown to be effective in promoting axonal regeneration and myelination, thereby promoting nerve injury repair. At present, it is considered that electric conduction recovery is a key aspect of regeneration and repair of long nerve defects. Conductive neural scaffolds have attracted more and more attention due to their similar electrical properties and good biocompatibility with normal nerves. Herein, PCL and MXene-PCL nerve guidance conduits (NGCs) were prepared; their effect on nerve regeneration was evaluated in vitro and in vivo . The results show that the NGCs have good biocompatibility in vitro . Furthermore, a sciatic nerve defect model (15 mm) of SD rats was made, and then the fabricated NGCs were implanted. MXene-PCL NGCs show similar results with the autograft in the sciatic function index, electrophysiological examination, angiogenesis, and morphological nerve regeneration. It is possible that the conductive MXene-PCL NGC could transmit physiological neural electric signals, induce angiogenesis, and stimulate nerve regeneration. This paper presents a novel design of MXene-PCL NGC that could transmit self-originated electric stimulation. In the future, it can be combined with other features to promote nerve regeneration.

研究领域: 神经科学 · 生物材料 · 组织工程 · 生物医学工程
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2014 · IF 3.107

Synthesis of Caffeic Acid Phenethyl Ester Derivatives, and Their Cytoprotective and Neuritogenic Activities in PC12 Cells

Haiming Shi,Dongsheng Xie,Ruoling Yang,Yaqian Cheng

Twenty-one caffeic acid phenethyl ester (CAPE) derivatives were synthesized, and characterized by IR, HR-MS, 1H and 13C NMR analyses. All compounds were evaluated for their cytoprotective effects against H2O2-induced cytotoxicity and neuritogenic activities in the neurite outgrowth in PC12 cells. Compounds 1 and 20 exhibited stronger cytoprotective activities than their parent compound CAPE at 4 nM. Compounds 1, 4, 12 and 13 showed potential neuritogenic activities at 0.5 nM, while compounds 19 and 20 induced neurite outgrowth at 10 nM. The results from this study suggested that CAPE and its derivatives may be potential functional food ingredients for the prevention of neurodegenerative diseases.

CAS / MDL: 10026-22-9
研究领域: 药理学 · 神经科学 · 有机化学
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EUROPEAN POLYMER JOURNAL · 2022 · IF 5.546

Mediate neurite outgrowth of PC-12 cells using polypyrrole-assisted laser-induced graphene flexible composite electrodes combined with electrical stimulation

Rongtao Liu,Zebiao Xu,Chen Zhao,Shiyang Zhang,Hongyu Zhou,Li Zhou,Yidong Liu,Yonggang Min

Although electrical stimulation (ES) has been proved to be an effective strategy in promoting the regeneration and repair of injured peripheral nerve tissue, it is still a big challenge to encounter the risk of inflammation and infection when the conductive biological platform directly contacted with the damaged tissue. Therefore, it is a very promising solution to develop non-invasive flexible electrodes’ bio-scaffolds for clinical treatment of nerve tissue regeneration combined with ES. With such purpose, the flexible composite electrodes by depositing polypyrrole on laser-induced graphene (LIG) have been developed. The proliferation and differentiation of PC-12 cells incubated on the prepared composite electrodes combined with an ES of 400 mV/cm at different times have also been investigated. The results showed that the fabricated composite electrodes exhibited excellent conductivity and wettability. Moreover, the essence of ES was to induce a field effect, namely, the cell proliferation was independent of the conductivity of the composite electrodes. In addition, we observed that ES could significantly enhance proliferation and differentiation of PC-12 cells. With the prolongation of ES time, the increasing trend finally stabilized. Importantly, the cell growth through MTT value was 1.37 when ES time was 4 h, and the increment was the largest, reaching 0.3, compared with that of 2 h. Furthermore, the cell differentiation showed that the neurite outgrowth length at 8 h of ES was the broadest distribution (the half-width ca 33.83 μm). And the average neurite length reached 68.39 μm after 8 h of ES, which increased by 16.26 μm compared with that of 4 h. This work inspires the design and construction of a practical conductive platform, and provided a new theoretical basis and data support for clinical therapy in nerve tissue engineering combined with ES.

研究领域: 生物医学工程 · 神经科学 · 组织工程 · 材料科学
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Pharmaceuticals · 2025 ·Vol. 18 ·期 11 ·1751 · IF 4.8

9-Methylfascaplysin, a Marine-Derived Bioactive Compound, Promotes Neurite Outgrowth via the Inhibition of ROCK2

Meilin Zheng,Kangyang Gao,Yirui Hong,Jingyang Le,Jingjing Cai,Hongze Liang,Wei Cui

Background:The impairment of neurite outgrowth is an early pathological hallmark underlying various neurodegenerative disorders. The promotion of neurite outgrowth was considered as a feasible strategy to treat neurodegenerative disorders. 9-Methylfascaplysin (9-MF), a marine-derived, bioactive compound, has exhibited multiple neuroprotective activities.Methods and Result:In this study, 9-MF at nanomolar concentrations promoted neurite outgrowth, upregulated the expression of growth-associated protein-43 (GAP-43), and increased the mitochondrial positive area with similar efficacy as retinoic acid in PC12 cells. 9-MF-associated differentiated expressed genes were enriched in mitochondria and synapse, forming a Rho-associated coiled-coil containing a protein kinase 2 (ROCK2)-centralized network. CMap analysis further identified positive connections between 9-MF-induced perturbation and perturbations caused by the inhibition of the ROCK2 pathway. Molecular docking analysis demonstrated a high binding affinity between 9-MF and ROCK2, indicating that 9-MF could inhibit ROCK2. Furthermore, 9-MF significantly reduced the phosphorylation of ROCK2 with a similar efficacy as fasudil, a ROCK2 inhibitor. Narciclasine, a known ROCK2 activator, almost completely abolished the effects of 9-MF on the induction of neurite outgrowth in PC12 cells.Conclusions:9-MF effectively promoted neurite outgrowth possibly via the inhibition of ROCK2, providing supporting evidence that 9-MF might be developed as a novel neurological drug.

CAS / MDL: 103745-39-7 302-79-4
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