Gualou Guizhi Granule inhibits microglia-mediated neuroinflammation to protect against neuronal apoptosis in vitro and in vivo
ObjectNeuroinflammation mediated by microglia has emerged as a critical factor in ischemic stroke and neuronal damage. Gualou Guizhi Granule (GLGZG) has been shown to suppress inflammation in lipopolysaccharide (LPS)-activated microglia, though the underlying mechanisms and its protective effects...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1527986/full |
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| author | Xuezhen Li Han Huang Yanan Li Yi Feng Jinxuan Wang Shuping Luo Yaping Chen Yuqin Zhang Guohong Yan Lihong Nan |
| author_facet | Xuezhen Li Han Huang Yanan Li Yi Feng Jinxuan Wang Shuping Luo Yaping Chen Yuqin Zhang Guohong Yan Lihong Nan |
| author_sort | Xuezhen Li |
| collection | DOAJ |
| description | ObjectNeuroinflammation mediated by microglia has emerged as a critical factor in ischemic stroke and neuronal damage. Gualou Guizhi Granule (GLGZG) has been shown to suppress inflammation in lipopolysaccharide (LPS)-activated microglia, though the underlying mechanisms and its protective effects against neuronal apoptosis remain unclear. This study aims to investigate how GLGZG regulates the Notch signaling pathway in microglia to reduce neuroinflammation and protect neurons from apoptosis.MethodUsing in vitro and in vivo models, we explored GLGZG's impact on microglia activation, pro-inflammatory cytokines, and neuronal apoptosis. Microglial cells were activated with LPS, and primary neuronal cells were exposed to LPS-activated microglia to simulate neuroinflammation. Additionally, we investigated the effects of GLGZG in combination with N-[N-[3,5-difluorophenacetyl]-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) or siRNA-Notch1 to further elucidate the involvement of the Notch signaling pathway.ResultsGLGZG significantly inhibited microglia activation and reduced neuroinflammation by de-creasing the levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α in both in vitro and in vivo models. GLGZG also effectively protected against microglia-induced neuronal apoptosis. Mechanistically, GLGZG down-regulated key components of the Notch signaling pathway, in-cluding Notch-1, NICD, RBPSUH, and Hes-1, in activated microglia. Combined treatment with GLGZG and DAPT or siRNA-Notch1 demonstrated enhanced inhibition of microglial activation and neuroinflammation.ConclusionOur findings reveal that GLGZG exerts its protective effects through the suppression of the Notch signaling pathway, thereby inhibiting microglia activation, reducing neuroinflammation, and safeguarding neurons from neuroinflammation-induced damage, offering potential as a therapeutic agent for ischemic stroke-induced neuroinflammation. |
| format | Article |
| id | doaj-art-ffca620f69834a0f8c2d4aebd880ac52 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-ffca620f69834a0f8c2d4aebd880ac522025-01-09T06:11:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15279861527986Gualou Guizhi Granule inhibits microglia-mediated neuroinflammation to protect against neuronal apoptosis in vitro and in vivoXuezhen Li0Han Huang1Yanan Li2Yi Feng3Jinxuan Wang4Shuping Luo5Yaping Chen6Yuqin Zhang7Guohong Yan8Lihong Nan9Institute of Structural Pharmacology and Traditional Chinese Medicine (TCM) Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaInstitute of Structural Pharmacology and Traditional Chinese Medicine (TCM) Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaInstitute of Structural Pharmacology and Traditional Chinese Medicine (TCM) Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaInstitute of Structural Pharmacology and Traditional Chinese Medicine (TCM) Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaPharmacy College, Fujian Medical University, Fuzhou, Fujian, ChinaInstitute of Structural Pharmacology and Traditional Chinese Medicine (TCM) Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaInstitute of Structural Pharmacology and Traditional Chinese Medicine (TCM) Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaInstitute of Structural Pharmacology and Traditional Chinese Medicine (TCM) Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaAffiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, ChinaInstitute of Structural Pharmacology and Traditional Chinese Medicine (TCM) Chemical Biology, Fujian Key Laboratory of Chinese Materia Medica, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, ChinaObjectNeuroinflammation mediated by microglia has emerged as a critical factor in ischemic stroke and neuronal damage. Gualou Guizhi Granule (GLGZG) has been shown to suppress inflammation in lipopolysaccharide (LPS)-activated microglia, though the underlying mechanisms and its protective effects against neuronal apoptosis remain unclear. This study aims to investigate how GLGZG regulates the Notch signaling pathway in microglia to reduce neuroinflammation and protect neurons from apoptosis.MethodUsing in vitro and in vivo models, we explored GLGZG's impact on microglia activation, pro-inflammatory cytokines, and neuronal apoptosis. Microglial cells were activated with LPS, and primary neuronal cells were exposed to LPS-activated microglia to simulate neuroinflammation. Additionally, we investigated the effects of GLGZG in combination with N-[N-[3,5-difluorophenacetyl]-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) or siRNA-Notch1 to further elucidate the involvement of the Notch signaling pathway.ResultsGLGZG significantly inhibited microglia activation and reduced neuroinflammation by de-creasing the levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α in both in vitro and in vivo models. GLGZG also effectively protected against microglia-induced neuronal apoptosis. Mechanistically, GLGZG down-regulated key components of the Notch signaling pathway, in-cluding Notch-1, NICD, RBPSUH, and Hes-1, in activated microglia. Combined treatment with GLGZG and DAPT or siRNA-Notch1 demonstrated enhanced inhibition of microglial activation and neuroinflammation.ConclusionOur findings reveal that GLGZG exerts its protective effects through the suppression of the Notch signaling pathway, thereby inhibiting microglia activation, reducing neuroinflammation, and safeguarding neurons from neuroinflammation-induced damage, offering potential as a therapeutic agent for ischemic stroke-induced neuroinflammation.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1527986/fullischemic strokeGualou Guizhi GranuleNotchmicroglianeuroinflammation |
| spellingShingle | Xuezhen Li Han Huang Yanan Li Yi Feng Jinxuan Wang Shuping Luo Yaping Chen Yuqin Zhang Guohong Yan Lihong Nan Gualou Guizhi Granule inhibits microglia-mediated neuroinflammation to protect against neuronal apoptosis in vitro and in vivo Frontiers in Immunology ischemic stroke Gualou Guizhi Granule Notch microglia neuroinflammation |
| title | Gualou Guizhi Granule inhibits microglia-mediated neuroinflammation to protect against neuronal apoptosis in vitro and in vivo |
| title_full | Gualou Guizhi Granule inhibits microglia-mediated neuroinflammation to protect against neuronal apoptosis in vitro and in vivo |
| title_fullStr | Gualou Guizhi Granule inhibits microglia-mediated neuroinflammation to protect against neuronal apoptosis in vitro and in vivo |
| title_full_unstemmed | Gualou Guizhi Granule inhibits microglia-mediated neuroinflammation to protect against neuronal apoptosis in vitro and in vivo |
| title_short | Gualou Guizhi Granule inhibits microglia-mediated neuroinflammation to protect against neuronal apoptosis in vitro and in vivo |
| title_sort | gualou guizhi granule inhibits microglia mediated neuroinflammation to protect against neuronal apoptosis in vitro and in vivo |
| topic | ischemic stroke Gualou Guizhi Granule Notch microglia neuroinflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1527986/full |
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