Resveratrol Inhibits Oxidative Stress and Regulates M1/M2-Type Polarization of Microglia via Mediation of the Nrf2/Shh Signaling Cascade after OGD/R Injury In Vitro
Aims: Microglia are closely related to the occurrence and development of oxidative stress. Cerebral ischemia leads to abnormal activation of microglia. Resveratrol can regulate M1/M2-type microglia polarization, but the underlying mechanism is not well understood, although the Nrf2 and Shh signaling...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | Journal of Personalized Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-4426/12/12/2087 |
| _version_ | 1797456766459445248 |
|---|---|
| author | Jie Liu Hongyan Liao Yue Chen Huimin Zhu Xuemei Li Jing Liu Qin Xiang Fanling Zeng Qin Yang |
| author_facet | Jie Liu Hongyan Liao Yue Chen Huimin Zhu Xuemei Li Jing Liu Qin Xiang Fanling Zeng Qin Yang |
| author_sort | Jie Liu |
| collection | DOAJ |
| description | Aims: Microglia are closely related to the occurrence and development of oxidative stress. Cerebral ischemia leads to abnormal activation of microglia. Resveratrol can regulate M1/M2-type microglia polarization, but the underlying mechanism is not well understood, although the Nrf2 and Shh signaling pathways may be involved. Given that resveratrol activates Shh, the present study examined whether this is mediated by Nrf2 signaling. Methods: N9 microglia were pretreated with drugs before oxygen-glucose deprivation/reoxygenation (OGD/R). HT22 neurons were also used for conditional co-culture with microglia. Cell viability was measured by CCK-8 assay. MDA levels and SOD activity in the supernatant were detected by TBA and WST-1, respectively. Immunofluorescence detected Nrf2 and Gli1 nuclear translocation. The levels of CD206, Arg1, iNOS, TNF-α, Nrf2, HO-1, NQO1, Shh, Ptc, Smo, Gli1 protein and mRNA were measured by Western blotting or RT-qPCR. Annexin V-FITC Flow Cytometric Analysis detected apoptosis. Results: Resveratrol and Nrf2 activator RTA-408 enhanced the viability of microglia, reduced oxidative stress, promoted M2-type microglia polarization and activated Nrf2 and Shh signaling. ML385, a selective inhibitor of Nrf2, decreased the viability of microglia, aggravated oxidative stress, promoted M1-type microglia polarization and inhibited Nrf2 and Shh signaling. Moreover, resveratrol and RTA-408-treated microglia can reduce the apoptosis and increase the viability of HT22 neurons, while ML385-treated microglia aggravated the apoptosis and weakened the viability of HT22 neurons. Conclusions: These results demonstrated that resveratrol may inhibit oxidative stress, regulate M1/M2-type polarization of microglia and decrease neuronal injury in conditional co-culture of neurons and microglia via the mediation of the Nrf2/Shh signaling cascade after OGD/R injury <i>in vitro</i>. |
| first_indexed | 2024-03-09T16:12:34Z |
| format | Article |
| id | doaj.art-06c6587d959047e489cce2791d706104 |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-09T16:12:34Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-06c6587d959047e489cce2791d7061042023-11-24T16:03:23ZengMDPI AGJournal of Personalized Medicine2075-44262022-12-011212208710.3390/jpm12122087Resveratrol Inhibits Oxidative Stress and Regulates M1/M2-Type Polarization of Microglia via Mediation of the Nrf2/Shh Signaling Cascade after OGD/R Injury In VitroJie Liu0Hongyan Liao1Yue Chen2Huimin Zhu3Xuemei Li4Jing Liu5Qin Xiang6Fanling Zeng7Qin Yang8Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, Longevity District People’s Hospital of Chongqing, Chongqing 401220, ChinaHealth Management Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, ChinaAims: Microglia are closely related to the occurrence and development of oxidative stress. Cerebral ischemia leads to abnormal activation of microglia. Resveratrol can regulate M1/M2-type microglia polarization, but the underlying mechanism is not well understood, although the Nrf2 and Shh signaling pathways may be involved. Given that resveratrol activates Shh, the present study examined whether this is mediated by Nrf2 signaling. Methods: N9 microglia were pretreated with drugs before oxygen-glucose deprivation/reoxygenation (OGD/R). HT22 neurons were also used for conditional co-culture with microglia. Cell viability was measured by CCK-8 assay. MDA levels and SOD activity in the supernatant were detected by TBA and WST-1, respectively. Immunofluorescence detected Nrf2 and Gli1 nuclear translocation. The levels of CD206, Arg1, iNOS, TNF-α, Nrf2, HO-1, NQO1, Shh, Ptc, Smo, Gli1 protein and mRNA were measured by Western blotting or RT-qPCR. Annexin V-FITC Flow Cytometric Analysis detected apoptosis. Results: Resveratrol and Nrf2 activator RTA-408 enhanced the viability of microglia, reduced oxidative stress, promoted M2-type microglia polarization and activated Nrf2 and Shh signaling. ML385, a selective inhibitor of Nrf2, decreased the viability of microglia, aggravated oxidative stress, promoted M1-type microglia polarization and inhibited Nrf2 and Shh signaling. Moreover, resveratrol and RTA-408-treated microglia can reduce the apoptosis and increase the viability of HT22 neurons, while ML385-treated microglia aggravated the apoptosis and weakened the viability of HT22 neurons. Conclusions: These results demonstrated that resveratrol may inhibit oxidative stress, regulate M1/M2-type polarization of microglia and decrease neuronal injury in conditional co-culture of neurons and microglia via the mediation of the Nrf2/Shh signaling cascade after OGD/R injury <i>in vitro</i>.https://www.mdpi.com/2075-4426/12/12/2087resveratrolmicrogliapolarizationoxidative stressNrf2 signalingShh signaling |
| spellingShingle | Jie Liu Hongyan Liao Yue Chen Huimin Zhu Xuemei Li Jing Liu Qin Xiang Fanling Zeng Qin Yang Resveratrol Inhibits Oxidative Stress and Regulates M1/M2-Type Polarization of Microglia via Mediation of the Nrf2/Shh Signaling Cascade after OGD/R Injury In Vitro Journal of Personalized Medicine resveratrol microglia polarization oxidative stress Nrf2 signaling Shh signaling |
| title | Resveratrol Inhibits Oxidative Stress and Regulates M1/M2-Type Polarization of Microglia via Mediation of the Nrf2/Shh Signaling Cascade after OGD/R Injury In Vitro |
| title_full | Resveratrol Inhibits Oxidative Stress and Regulates M1/M2-Type Polarization of Microglia via Mediation of the Nrf2/Shh Signaling Cascade after OGD/R Injury In Vitro |
| title_fullStr | Resveratrol Inhibits Oxidative Stress and Regulates M1/M2-Type Polarization of Microglia via Mediation of the Nrf2/Shh Signaling Cascade after OGD/R Injury In Vitro |
| title_full_unstemmed | Resveratrol Inhibits Oxidative Stress and Regulates M1/M2-Type Polarization of Microglia via Mediation of the Nrf2/Shh Signaling Cascade after OGD/R Injury In Vitro |
| title_short | Resveratrol Inhibits Oxidative Stress and Regulates M1/M2-Type Polarization of Microglia via Mediation of the Nrf2/Shh Signaling Cascade after OGD/R Injury In Vitro |
| title_sort | resveratrol inhibits oxidative stress and regulates m1 m2 type polarization of microglia via mediation of the nrf2 shh signaling cascade after ogd r injury in vitro |
| topic | resveratrol microglia polarization oxidative stress Nrf2 signaling Shh signaling |
| url | https://www.mdpi.com/2075-4426/12/12/2087 |
| work_keys_str_mv | AT jieliu resveratrolinhibitsoxidativestressandregulatesm1m2typepolarizationofmicrogliaviamediationofthenrf2shhsignalingcascadeafterogdrinjuryinvitro AT hongyanliao resveratrolinhibitsoxidativestressandregulatesm1m2typepolarizationofmicrogliaviamediationofthenrf2shhsignalingcascadeafterogdrinjuryinvitro AT yuechen resveratrolinhibitsoxidativestressandregulatesm1m2typepolarizationofmicrogliaviamediationofthenrf2shhsignalingcascadeafterogdrinjuryinvitro AT huiminzhu resveratrolinhibitsoxidativestressandregulatesm1m2typepolarizationofmicrogliaviamediationofthenrf2shhsignalingcascadeafterogdrinjuryinvitro AT xuemeili resveratrolinhibitsoxidativestressandregulatesm1m2typepolarizationofmicrogliaviamediationofthenrf2shhsignalingcascadeafterogdrinjuryinvitro AT jingliu resveratrolinhibitsoxidativestressandregulatesm1m2typepolarizationofmicrogliaviamediationofthenrf2shhsignalingcascadeafterogdrinjuryinvitro AT qinxiang resveratrolinhibitsoxidativestressandregulatesm1m2typepolarizationofmicrogliaviamediationofthenrf2shhsignalingcascadeafterogdrinjuryinvitro AT fanlingzeng resveratrolinhibitsoxidativestressandregulatesm1m2typepolarizationofmicrogliaviamediationofthenrf2shhsignalingcascadeafterogdrinjuryinvitro AT qinyang resveratrolinhibitsoxidativestressandregulatesm1m2typepolarizationofmicrogliaviamediationofthenrf2shhsignalingcascadeafterogdrinjuryinvitro |