Scutellarin ameliorates neonatal hypoxic-ischemic encephalopathy associated with GAP43-dependent signaling pathway
Abstract Background Neonatal hypoxic-ischemic encephalopathy (HIE) refers to the perinatal asphyxia caused by the cerebral hypoxic-ischemic injury. The current study was aimed at investigating the therapeutic efficacy of Scutellarin (Scu) administration on neurological impairments induced by hypoxic...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-10-01
|
| Series: | Chinese Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13020-021-00517-z |
| _version_ | 1819292163046899712 |
|---|---|
| author | Rui-Ze Niu Liu-Lin Xiong Hao-Li Zhou Lu-Lu Xue Qing-Jie Xia Zheng Ma Yuan Jin Li Chen Ya Jiang Ting-Hua Wang Jia Liu |
| author_facet | Rui-Ze Niu Liu-Lin Xiong Hao-Li Zhou Lu-Lu Xue Qing-Jie Xia Zheng Ma Yuan Jin Li Chen Ya Jiang Ting-Hua Wang Jia Liu |
| author_sort | Rui-Ze Niu |
| collection | DOAJ |
| description | Abstract Background Neonatal hypoxic-ischemic encephalopathy (HIE) refers to the perinatal asphyxia caused by the cerebral hypoxic-ischemic injury. The current study was aimed at investigating the therapeutic efficacy of Scutellarin (Scu) administration on neurological impairments induced by hypoxic-ischemic injury and exploring the underlying mechanisms. Methods Primary cortical neurons were cultured and subjected to oxygen–glucose deprivation (OGD), and then treated with Scu administration. The growth status of neurons was observed by immunofluorescence staining of TUJ1 and TUNEL. Besides, the mRNA level of growth-associated protein 43 (GAP43) in OGD neurons with Scu treatment was detected by quantitative real-time polymerase chain reaction (qRT-PCR). To further verify the role of GAP43 in Scu treatment, GAP43 siRNA and knockout were applied in vitro and in vivo. Moreover, behavioral evaluations were performed to elucidate the function of GAP43 in the Scu-ameliorated long-term neurological impairments caused by HI insult. The underlying biological mechanism of Scu treatment was further elucidated via network pharmacological analysis. Finally, the interactive genes with GAP43 were identified by Gene MANIA and further validated by qRT-PCR. Results Our data demonstrated that Scu treatment increased the number of neurons and axon growth, and suppressed cell apoptosis in vitro. And the expression of GAP43 was downregulated after OGD, but reversed by Scu administration. Besides, GAP43 silencing aggravated the Scu-ameliorated neuronal death and axonal damage. Meanwhile, GAP43 knockout enlarged brain infarct area and deteriorated the cognitive and motor dysfunctions of HI rats. Further, network pharmacological analysis revealed the drug targets of Scu participated in such biological processes as neuronal death and regulation of neuronal death, and apoptosis-related pathways. GAP43 exhibited close relationship with PTN, JAK2 and STAT3, and GAP43 silencing upregulated the levels of PTN, JAK2 and STAT3. Conclusions Collectively, our findings revealed Scu treatment attenuated long-term neurological impairments after HI by suppressing neuronal death and enhancing neurite elongation through GAP43-dependent pathway. The crucial role of Scutellarin in neuroprotection provided a novel possible therapeutic agent for the treatment of neonatal HIE. Graphic abstract |
| first_indexed | 2024-12-24T03:50:09Z |
| format | Article |
| id | doaj.art-d4537725441a42519ba239dbc2428080 |
| institution | Directory Open Access Journal |
| issn | 1749-8546 |
| language | English |
| last_indexed | 2024-12-24T03:50:09Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Chinese Medicine |
| spelling | doaj.art-d4537725441a42519ba239dbc24280802022-12-21T17:16:37ZengBMCChinese Medicine1749-85462021-10-0116111210.1186/s13020-021-00517-zScutellarin ameliorates neonatal hypoxic-ischemic encephalopathy associated with GAP43-dependent signaling pathwayRui-Ze Niu0Liu-Lin Xiong1Hao-Li Zhou2Lu-Lu Xue3Qing-Jie Xia4Zheng Ma5Yuan Jin6Li Chen7Ya Jiang8Ting-Hua Wang9Jia Liu10Animal Zoology Department, Kunming Medical UniversityInstitute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan UniversityThe Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, University of Electronic Science and Technology of ChinaInstitute of Neuroscience, Kunming Medical UniversityInstitute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan UniversityInstitute of Neuroscience, Kunming Medical UniversityInstitute of Neuroscience, Kunming Medical UniversityInstitute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan UniversityAnimal Zoology Department, Kunming Medical UniversityAnimal Zoology Department, Kunming Medical UniversityAnimal Zoology Department, Kunming Medical UniversityAbstract Background Neonatal hypoxic-ischemic encephalopathy (HIE) refers to the perinatal asphyxia caused by the cerebral hypoxic-ischemic injury. The current study was aimed at investigating the therapeutic efficacy of Scutellarin (Scu) administration on neurological impairments induced by hypoxic-ischemic injury and exploring the underlying mechanisms. Methods Primary cortical neurons were cultured and subjected to oxygen–glucose deprivation (OGD), and then treated with Scu administration. The growth status of neurons was observed by immunofluorescence staining of TUJ1 and TUNEL. Besides, the mRNA level of growth-associated protein 43 (GAP43) in OGD neurons with Scu treatment was detected by quantitative real-time polymerase chain reaction (qRT-PCR). To further verify the role of GAP43 in Scu treatment, GAP43 siRNA and knockout were applied in vitro and in vivo. Moreover, behavioral evaluations were performed to elucidate the function of GAP43 in the Scu-ameliorated long-term neurological impairments caused by HI insult. The underlying biological mechanism of Scu treatment was further elucidated via network pharmacological analysis. Finally, the interactive genes with GAP43 were identified by Gene MANIA and further validated by qRT-PCR. Results Our data demonstrated that Scu treatment increased the number of neurons and axon growth, and suppressed cell apoptosis in vitro. And the expression of GAP43 was downregulated after OGD, but reversed by Scu administration. Besides, GAP43 silencing aggravated the Scu-ameliorated neuronal death and axonal damage. Meanwhile, GAP43 knockout enlarged brain infarct area and deteriorated the cognitive and motor dysfunctions of HI rats. Further, network pharmacological analysis revealed the drug targets of Scu participated in such biological processes as neuronal death and regulation of neuronal death, and apoptosis-related pathways. GAP43 exhibited close relationship with PTN, JAK2 and STAT3, and GAP43 silencing upregulated the levels of PTN, JAK2 and STAT3. Conclusions Collectively, our findings revealed Scu treatment attenuated long-term neurological impairments after HI by suppressing neuronal death and enhancing neurite elongation through GAP43-dependent pathway. The crucial role of Scutellarin in neuroprotection provided a novel possible therapeutic agent for the treatment of neonatal HIE. Graphic abstracthttps://doi.org/10.1186/s13020-021-00517-zScutellarinHypoxic-ischemic encephalopathyGAP43Neuroprotection |
| spellingShingle | Rui-Ze Niu Liu-Lin Xiong Hao-Li Zhou Lu-Lu Xue Qing-Jie Xia Zheng Ma Yuan Jin Li Chen Ya Jiang Ting-Hua Wang Jia Liu Scutellarin ameliorates neonatal hypoxic-ischemic encephalopathy associated with GAP43-dependent signaling pathway Chinese Medicine Scutellarin Hypoxic-ischemic encephalopathy GAP43 Neuroprotection |
| title | Scutellarin ameliorates neonatal hypoxic-ischemic encephalopathy associated with GAP43-dependent signaling pathway |
| title_full | Scutellarin ameliorates neonatal hypoxic-ischemic encephalopathy associated with GAP43-dependent signaling pathway |
| title_fullStr | Scutellarin ameliorates neonatal hypoxic-ischemic encephalopathy associated with GAP43-dependent signaling pathway |
| title_full_unstemmed | Scutellarin ameliorates neonatal hypoxic-ischemic encephalopathy associated with GAP43-dependent signaling pathway |
| title_short | Scutellarin ameliorates neonatal hypoxic-ischemic encephalopathy associated with GAP43-dependent signaling pathway |
| title_sort | scutellarin ameliorates neonatal hypoxic ischemic encephalopathy associated with gap43 dependent signaling pathway |
| topic | Scutellarin Hypoxic-ischemic encephalopathy GAP43 Neuroprotection |
| url | https://doi.org/10.1186/s13020-021-00517-z |
| work_keys_str_mv | AT ruizeniu scutellarinamelioratesneonatalhypoxicischemicencephalopathyassociatedwithgap43dependentsignalingpathway AT liulinxiong scutellarinamelioratesneonatalhypoxicischemicencephalopathyassociatedwithgap43dependentsignalingpathway AT haolizhou scutellarinamelioratesneonatalhypoxicischemicencephalopathyassociatedwithgap43dependentsignalingpathway AT luluxue scutellarinamelioratesneonatalhypoxicischemicencephalopathyassociatedwithgap43dependentsignalingpathway AT qingjiexia scutellarinamelioratesneonatalhypoxicischemicencephalopathyassociatedwithgap43dependentsignalingpathway AT zhengma scutellarinamelioratesneonatalhypoxicischemicencephalopathyassociatedwithgap43dependentsignalingpathway AT yuanjin scutellarinamelioratesneonatalhypoxicischemicencephalopathyassociatedwithgap43dependentsignalingpathway AT lichen scutellarinamelioratesneonatalhypoxicischemicencephalopathyassociatedwithgap43dependentsignalingpathway AT yajiang scutellarinamelioratesneonatalhypoxicischemicencephalopathyassociatedwithgap43dependentsignalingpathway AT tinghuawang scutellarinamelioratesneonatalhypoxicischemicencephalopathyassociatedwithgap43dependentsignalingpathway AT jialiu scutellarinamelioratesneonatalhypoxicischemicencephalopathyassociatedwithgap43dependentsignalingpathway |