Oleanolic Acid Inhibiting the Differentiation of Neural Stem Cells into Astrocyte by Down-Regulating JAK/STAT Signaling Pathway

Zhang, Yulian; Zhou, Zhen; Han, Wenwen; Zhang, Linlin; Song, Wei; Huang, Jianhua; Liu, Shuang

doi:10.1142/s0192415x16500075

Cited by 18 publications

(9 citation statements)

References 35 publications

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“…Gentiopicrin (CAS:20831-76-9), loganic acid (CAS: 22255-40-9), swertamarin (CAS: 1738839-5); loganin (CAS: 18524-94-2), vitexin (CAS: 3681-93-4), sweroside (CAS: 14215-86-2), and 6 -O-β-dglucopyranosylgentiopicroside (CAS: 115713-06-9) were purchased from Biopurify Phytochemicals Ltd. (Chengdu, China). The purity of all of the standards is higher than 98% (determined by HPLC), and were confirmed by the 1 H-NMR spectra to those in the literature [14][15][16][17][18][19][20].…”

Section: Plant Materials Reagents and Chemicalssupporting

confidence: 75%

“…Gentiopicroside, swertiamarin, 6 -O-β-d-glucopyranosyl-gentiopicroside, sweroside, loganic acide and loganin were identified by comparison with the retention time and mass fragmentation of reference standards. The SciFinder Scholar and the PubChem databases were searched for the spectral data of other compounds reported previously in the genus Gentiana and G. straminea to identify the constituents of the herb [14][15][16][17][18][19][20]. Forty-three of these were identified by comparing the retention times and mass spectrometry, which has already been summarized [21], including 20 iridoids, 16 secoiridoids, 8 flavonoids, 2 triterpenoids, 2 lignins, 2 alkaloids, and 2 saccharides (Table 1).…”

Section: Identification Of the Constituents In G Straminea By Uplc-qmentioning

confidence: 99%

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Traceability of Geographical Origin in Gentiana straminea by UPLC-Q Exactive Mass and Multivariate Analyses

et al. 2019

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The root of Gentiana straminea Maxim. (Gentianaceae), is officially listed as “Qin-Jiao” in the Chinese Pharmacopoeia for the treatment of rheumatic arthritis, icteric hepatitis, constipation, pain, and hypertension. To establish the geographical origin traceability in G. straminea, its chemical profiles were determined by a UPLC-Q exactive mass spectrometer, from which 43 compounds were identified by comparing retention times and mass spectrometry. Meanwhile, a pair of isomers (loganin and secologanol) was identified by mass spectrometry based on their fragmentation pathway. A total of 42 samples from difference habitats were determined by an UPLC-Q exactive mass spectrometer and the data were assayed with multivariate statistical analysis. Eight characteristic compounds were identified to determine the geographical origin of the herb. To estimate the key characteristic markers associated with pharmacological function, the inhibiting activities of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced macrophages were examined. This finding is crucial in realizing the determination of botanical origin and evaluating the quality of G. straminea.

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Section: Plant Materials Reagents and Chemicalssupporting

confidence: 75%

Section: Identification Of the Constituents In G Straminea By Uplc-qmentioning

confidence: 99%

Traceability of Geographical Origin in Gentiana straminea by UPLC-Q Exactive Mass and Multivariate Analyses

et al. 2019

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“…This cascade is responsible for the activation of GFAP gene by many factors, such as cholera toxin and interleukin (IL)‐6 in C6 malignant glioma cells (Shu et al, ), oncostatin M (OSM) in cortical neurons (Moidunny et al, ), epidermal growth factor in human glioblastoma (He et al, ), and IL‐33 in spinal glia (Du et al, ). In contrast, the inhibition of astrocyte proliferation and GFAP expression is due to suppression of JAK2/STAT3 pathway by some other factors, such as sevoflurane in the hippocampus of neonatal rats (Wang, Lu, Feng, & Zhang, ), oleanolic acid in neural stem cells (Zhang et al, ), and SN79 in striatum in mice (Robson et al, ).…”

Section: Expression Of Gfap and Its Regulationmentioning

confidence: 99%

Neurochemical regulation of the expression and function of glial fibrillary acidic protein in astrocytes

Liu

et al. 2019

Glia

116

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Glial fibrillary acidic protein (GFAP), a type III intermediate filament, is a marker of mature astrocytes. The expression of GFAP gene is regulated by many transcription factors (TFs), mainly Janus kinase‐2/signal transducer and activator of transcription 3 cascade and nuclear factor κ‐light‐chain‐enhancer of activated B cell signaling. GFAP expression is also modulated by protein kinase and other signaling molecules that are elicited by neuronal activity and hormones. Abnormal expression of GFAP proteins occurs in neuroinflammation, neurodegeneration, brain edema‐eliciting diseases, traumatic brain injury, psychiatric disorders and others. GFAP, mainly in α‐isoform, is the major component of cytoskeleton and the scaffold of astrocytes, which is essential for the maintenance of astrocytic structure and shape. GFAP also has highly morphological plasticity because of its quick changes in assembling and polymerizing states in response to environmental challenges. This plasticity and its corresponding cellular morphological changes endow astrocytes the functions of physical barrier between adjacent neurons and stabilizer of extracellular environment. Moreover, GFAP colocalizes and even molecularly associates with many functional molecules. This feature allows GFAP to function as a platform for direct interactions between different molecules. Last, GFAP involves transportation and localization of other functional proteins and thus serves as a protein transport guide in astrocytes. This guiding role of GFAP involves an elastic retraction and extension cytoskeletal network that couples with GFAP reassembling, transporting, and membrane protein recycling machinery. This paper reviews our current understanding of the expression and functions of GFAP as well as their regulation.

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“…Furthermore, several studies suggest that inhibition of JAK-STAT pathway can induce fate switch and facilitate neuronal differentiation [38, 39]. We have demonstrated that astrocytic CM stimulation activates JAK-STAT pathway, while blocking LIF and CNTF in astrocytic CM significantly repress such activation leading to the increase of neuronal differentiation.…”

Section: Discussionmentioning

confidence: 72%

miR-17-92 facilitates neuronal differentiation of transplanted neural stem/precursor cells under neuroinflammatory conditions

Mao

Wang

et al. 2016

J Neuroinflammation

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BackgroundNeural stem/precursor cells (NSCs) are of particular interest because of their potential application in cell therapy for brain damage. However, most brain injury cases are followed with neuroinflammatory stress, which affects the lineage selection of grafted NSCs by promoting astrocytogenesis, thus hampering the potential for neural replacement. The present study investigated the role of miR-17-92 in protecting against detrimental effects of neuroinflammation on NSC differentiation in cell therapy.MethodsNSCs were treated with conditioned medium from lesioned astrocytes with/without neutralizing antibodies of leukemia inhibitory factor (LIF) or/and ciliary neurotrophic factor (CNTF), respectively. Afterward, the levels of p-STAT3 and p-JAK2 were determined by western blotting while expression of glial fibrillary acidic protein (GFAP) and β-tubulin III was assessed by immunostaining. The activation of JAK-STAT pathway and cell differentiation were also evaluated after we overexpressed miR-17-92 in NSCs under different neuroinflammatory conditions. After the transplantation of miR-17-92-overexpressing NSCs into injured mouse cortex, PH3, nestin, GFAP, and NeuN were analyzed by immunostaining. In addition, motor coordination of mice was evaluated by rotarod test.ResultsConditioned medium from lesioned astrocytes activated JAK-STAT pathway and facilitated astrocytic differentiation in NSCs while neutralizing antibodies of LIF and CNTF remarkably attenuated such effects. miR-17-92 cluster repressed the expression of multiple proteins including GP130, CNTFR, JAK2, and STAT3 in JAK-STAT pathway. Overexpression of miR-17-92 in NSCs systematically blocked the activation of JAK-STAT pathway mediated by LIF and CNTF, which facilitated neuronal differentiation in vitro. Furthermore, miR-17-92 increased neuronal generation of grafted NSCs and reduced astrogliosis, which resulted in the improvement of motor coordination of brain-injured mice.ConclusionsOur results suggest that miR-17-92 promotes neuronal differentiation of grafted NSCs under neuroinflammatory condition via inhibition of multiple proteins in JAK-STAT pathway.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0685-5) contains supplementary material, which is available to authorized users.

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Oleanolic Acid Inhibiting the Differentiation of Neural Stem Cells into Astrocyte by Down-Regulating JAK/STAT Signaling Pathway

Cited by 18 publications

References 35 publications

Traceability of Geographical Origin in Gentiana straminea by UPLC-Q Exactive Mass and Multivariate Analyses

Traceability of Geographical Origin in Gentiana straminea by UPLC-Q Exactive Mass and Multivariate Analyses

Neurochemical regulation of the expression and function of glial fibrillary acidic protein in astrocytes

miR-17-92 facilitates neuronal differentiation of transplanted neural stem/precursor cells under neuroinflammatory conditions

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