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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Nutritional Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1527986
This article is part of the Research Topic Foods, Dietary Supplements, and Herbal Products Treating the Diseases of the 21st Century: Moving from Traditional to Scientific Research: Volume II View all 11 articles

Gualou Guizhi Granule inhibits microglia-mediated neuroinflammation to protect against neuronal apoptosis in vitro and in vivo

Provisionally accepted
Xuezhen Li Xuezhen Li 1*Han Huang Han Huang 1*Yanan Li Yanan Li 1*Yi Feng Yi Feng 1*Jinxuan Wang Jinxuan Wang 2*Shuping Luo Shuping Luo 1*Yaping Chen Yaping Chen 1*Yuqin Zhang Yuqin Zhang 1*Guohong Yan Guohong Yan 3*Lihong Nan Lihong Nan 1*
  • 1 Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, China
  • 2 Fujian Medical University, Fuzhou, Fujian Province, China
  • 3 Third Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, China

The final, formatted version of the article will be published soon.

    Neuroinflammation 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. Using 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]-Sphenylglycine t-butyl ester (DAPT) or siRNA-Notch1 to further elucidate the involvement of the Notch signaling pathway. GLGZG 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. Our 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.

    Keywords: ischemic stroke, GualouGuizhi Granule, Notch, Microglia, Neuroinflammation

    Received: 14 Nov 2024; Accepted: 17 Dec 2024.

    Copyright: © 2024 Li, Huang, Li, Feng, Wang, Luo, Chen, Zhang, Yan and Nan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Xuezhen Li, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian Province, China
    Han Huang, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian Province, China
    Yanan Li, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian Province, China
    Yi Feng, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian Province, China
    Jinxuan Wang, Fujian Medical University, Fuzhou, 350108, Fujian Province, China
    Shuping Luo, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian Province, China
    Yaping Chen, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian Province, China
    Yuqin Zhang, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian Province, China
    Guohong Yan, Third Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian Province, China
    Lihong Nan, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian Province, China

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