GAS reduced inflammatory responses in activated microglia by regulating the Ccr2/Akt/Gsk-3β pathway
Abstract Hypoxic-ischemic brain damage (HIBD) is a significant cause of neonatal death and neurological dysfunction. Following this injury, activated microglia can lead to a series of inflammatory responses. Gastrodin (GAS), a polyphenol extracted from the Chinese herbal medicine Gastrodia elata Blu...
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BMC
2025-05-01
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| Series: | Molecular Brain |
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| Online Access: | https://doi.org/10.1186/s13041-025-01206-w |
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| author | Haolong Shi Jinsha Shi Zhao Wang Hanjun Zuo Tao Guo Huixin Zheng Rong Xiao Xinglin Zhang Shuhan Yang Juanjuan Li |
| author_facet | Haolong Shi Jinsha Shi Zhao Wang Hanjun Zuo Tao Guo Huixin Zheng Rong Xiao Xinglin Zhang Shuhan Yang Juanjuan Li |
| author_sort | Haolong Shi |
| collection | DOAJ |
| description | Abstract Hypoxic-ischemic brain damage (HIBD) is a significant cause of neonatal death and neurological dysfunction. Following this injury, activated microglia can lead to a series of inflammatory responses. Gastrodin (GAS), a polyphenol extracted from the Chinese herbal medicine Gastrodia elata Blume, has demonstrated antioxidant and anti-inflammatory effects. This study investigated the neuroprotective impact of GAS in HIBD mice model and in BV2 cells subjected to oxygen-glucose deprivation (OGD) treatment. Expression of various members of the Ccr2/Akt/Gsk-3β, including Ccl2, Ccr2, Akt, p-Akt, Gsk-3β, p-Gsk-3β and inflammatory factors TNF-α and IL-1β in activated microglia was assessed by Western blotting, immunofluorescence, and qRT-PCR in HIBD in postnatal mice, and in OGD-induced BV2 microglia in vitro with or without GAS treatment. The present results showed that GAS effectively reduces the expression of Ccl2 and Ccr2, increases the phosphorylation levels of Akt and Gsk-3β, and decreases the expression of the TNF-α and IL-1β. Additionally, we have shown that inhibition of Ccr2 by RS102895 increased the expression of p-Akt and p-Gsk-3β, and attenuate production of proinflammatory mediators in activated microglia. Of note, the expression of p-Akt, p-Gsk-3β, TNF-α and IL-1β remained unchanged after the combination of gastrodin and RS102895. Taken together, we conclude that GAS can play a protective role in reducing the neuroinflammatory response after HIBD. It is suggested that this is mainly through up-regulating the Akt/Gsk-3β signaling pathway via the Ccr2 receptor in the present experimental paradigm. |
| format | Article |
| id | doaj-art-4a04a7c45ee54bf283f41186a9fa7d35 |
| institution | Kabale University |
| issn | 1756-6606 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj-art-4a04a7c45ee54bf283f41186a9fa7d352025-08-20T03:53:16ZengBMCMolecular Brain1756-66062025-05-0118111310.1186/s13041-025-01206-wGAS reduced inflammatory responses in activated microglia by regulating the Ccr2/Akt/Gsk-3β pathwayHaolong Shi0Jinsha Shi1Zhao Wang2Hanjun Zuo3Tao Guo4Huixin Zheng5Rong Xiao6Xinglin Zhang7Shuhan Yang8Juanjuan Li9Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Sciences, Kunming Medical UniversityDepartment of Anatomy and Histology & Embryology, Faculty of Basic Medical Sciences, Kunming Medical UniversityDepartment of Anatomy and Histology & Embryology, Faculty of Basic Medical Sciences, Kunming Medical UniversityDepartment of Anatomy and Histology & Embryology, Faculty of Basic Medical Sciences, Kunming Medical UniversityDepartment of Anatomy and Histology & Embryology, Faculty of Basic Medical Sciences, Kunming Medical UniversityDepartment of Anatomy and Histology & Embryology, Faculty of Basic Medical Sciences, Kunming Medical UniversityDepartment of Anatomy and Histology & Embryology, Faculty of Basic Medical Sciences, Kunming Medical UniversityDepartment of Anatomy and Histology & Embryology, Faculty of Basic Medical Sciences, Kunming Medical UniversityDepartment of Anatomy and Histology & Embryology, Faculty of Basic Medical Sciences, Kunming Medical UniversityDepartment of Anatomy and Histology & Embryology, Faculty of Basic Medical Sciences, Kunming Medical UniversityAbstract Hypoxic-ischemic brain damage (HIBD) is a significant cause of neonatal death and neurological dysfunction. Following this injury, activated microglia can lead to a series of inflammatory responses. Gastrodin (GAS), a polyphenol extracted from the Chinese herbal medicine Gastrodia elata Blume, has demonstrated antioxidant and anti-inflammatory effects. This study investigated the neuroprotective impact of GAS in HIBD mice model and in BV2 cells subjected to oxygen-glucose deprivation (OGD) treatment. Expression of various members of the Ccr2/Akt/Gsk-3β, including Ccl2, Ccr2, Akt, p-Akt, Gsk-3β, p-Gsk-3β and inflammatory factors TNF-α and IL-1β in activated microglia was assessed by Western blotting, immunofluorescence, and qRT-PCR in HIBD in postnatal mice, and in OGD-induced BV2 microglia in vitro with or without GAS treatment. The present results showed that GAS effectively reduces the expression of Ccl2 and Ccr2, increases the phosphorylation levels of Akt and Gsk-3β, and decreases the expression of the TNF-α and IL-1β. Additionally, we have shown that inhibition of Ccr2 by RS102895 increased the expression of p-Akt and p-Gsk-3β, and attenuate production of proinflammatory mediators in activated microglia. Of note, the expression of p-Akt, p-Gsk-3β, TNF-α and IL-1β remained unchanged after the combination of gastrodin and RS102895. Taken together, we conclude that GAS can play a protective role in reducing the neuroinflammatory response after HIBD. It is suggested that this is mainly through up-regulating the Akt/Gsk-3β signaling pathway via the Ccr2 receptor in the present experimental paradigm.https://doi.org/10.1186/s13041-025-01206-wGASMicrogliaHypoxic-ischemic brain damageCcr2/Akt/Gsk-3β |
| spellingShingle | Haolong Shi Jinsha Shi Zhao Wang Hanjun Zuo Tao Guo Huixin Zheng Rong Xiao Xinglin Zhang Shuhan Yang Juanjuan Li GAS reduced inflammatory responses in activated microglia by regulating the Ccr2/Akt/Gsk-3β pathway Molecular Brain GAS Microglia Hypoxic-ischemic brain damage Ccr2/Akt/Gsk-3β |
| title | GAS reduced inflammatory responses in activated microglia by regulating the Ccr2/Akt/Gsk-3β pathway |
| title_full | GAS reduced inflammatory responses in activated microglia by regulating the Ccr2/Akt/Gsk-3β pathway |
| title_fullStr | GAS reduced inflammatory responses in activated microglia by regulating the Ccr2/Akt/Gsk-3β pathway |
| title_full_unstemmed | GAS reduced inflammatory responses in activated microglia by regulating the Ccr2/Akt/Gsk-3β pathway |
| title_short | GAS reduced inflammatory responses in activated microglia by regulating the Ccr2/Akt/Gsk-3β pathway |
| title_sort | gas reduced inflammatory responses in activated microglia by regulating the ccr2 akt gsk 3β pathway |
| topic | GAS Microglia Hypoxic-ischemic brain damage Ccr2/Akt/Gsk-3β |
| url | https://doi.org/10.1186/s13041-025-01206-w |
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