Wogonoside (WG) is a natural flavonoid extracted from Scutellariae Radix, recognized for its established anti-inflammatory properties. However, the role of WG in the context of neuroinflammation after spinal cord injury (SCI) remains inadequately elucidated. This study employed in silico, in vitro, and in vivo methodologies to investigate the impact of WG on microglia-mediated neuroinflammation after SCI. In the in silico experiment, we identified 15 potential target genes of WG associated with SCI. These genes were linked to the regulation of inflammatory response and immune defense. Molecular docking maps revealed toll-like receptor 4 as a molecular target for WG, demonstrating binding through a hydrogen bond (Lys263, Ser120). In lipopolysaccharide-stimulated BV2 cells and SCI mice, WG significantly attenuated microglial activation and facilitated a phenotype shift from M1 to M2. This was evidenced by the reversal of the increased expressions of Iba1, GFAP, and iNOS, as well as the decreased expression of Arg1. WG also suppressed the production of pro-inflammatory mediators (NO, TNF-α, IL-6, IL-1α, IL-1β, C1q). WG exerted these effects by suppressing the TLR4/MyD88/NF-κB signaling axis in microglia. Furthermore, by reducing levels of TNF-α, IL-1α, and C1q in supernatant of LPS-induced microglia, WG indirectly induced astrocytes change to A2 phenotype, evidenced by transcriptome sequencing result of primary mouse astrocytes. All these events above collectively created a favorable microenvironment, contributing to a significant alleviation of weight loss and neuronal damage at the lesion site of SCI mice. Our findings substantiate the efficacy of WG in mitigating neuroinflammation after SCI, thereby warranting further exploration.
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http://dx.doi.org/10.1016/j.ejphar.2024.176566 | DOI Listing |
Int Immunopharmacol
December 2024
Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210008, China; Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China. Electronic address:
Microglia, the primary immune cells of the central nervous system, play a crucial role in the neuroinflammatory processes following ischemic stroke. Targeting neuroinflammation is a promising strategy to enhance the outcomes of ischemic stroke. Benzydamine (BA), a well-known non-steroidal anti-inflammatory drug, has demonstrated potential in inhibiting pro-inflammatory cytokines across various disease models.
View Article and Find Full Text PDFPerioperative neurocognitive disorder (PND) is a common complication in the perioperative period, which not only prolongs the hospitalization of patients, increases the cost of treatment, but even increases the postoperative mortality of patients, bringing a heavy burden to families and society. Mechanism exploration involves anesthesia and surgery that lead to microglial activation, promote the synthesis and secretion of inflammatory factors, cause an inflammatory cascade, aggravate nerve cell damage, and lead to cognitive dysfunction. It is believed that microglia-mediated neuroinflammatory responses play a vital role in the formation of PND.
View Article and Find Full Text PDFCell Biol Int
December 2024
Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Mounting evidence indicates the involvement of N6-methyladenosine (m6A) alterations in diverse neurological disorders and the activation of microglia. However, the role of m6A methyltransferase Wilms' tumor 1-associated protein (WTAP) in regulating microglial polarization during ischemic stroke (IS) remains unknown. We performed bioinformatics analysis to identify m6A-related differentially expressed genes in IS and validated these genes in a mouse middle cerebral artery occlusion model and a BV2 cell oxygen-glucose deprivation/reperfusion model.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Unidad de Cartografía Cerebral, Instituto Pluridisciplinar, Universidad Complutense de Madrid, 28040 Madrid, Spain.
4-aminopyridine (4-AP) is a non-selective blocker of voltage-dependent K channels used to improve walking in multiple sclerosis patients, and it may be useful in the treatment of cerebellar diseases. In animal models, 4-AP is used as a convulsant agent. When administered intrahippocampally, 4-AP induces acute local glucose hypermetabolism and significant brain damage, while i.
View Article and Find Full Text PDFDrug Dev Res
December 2024
Department of Spine Surgery, Shenzhen Pingle Orthopedic Hospital, Affiliated Hospital of Guangzhou University of Chinese Medicine, Shenzhen, China.
Microglia-mediated neuroinflammatory responses have a critical function in the spinal cord injury (SCI) mechanism, and targeted modulation of microglia activity has emerged as a new therapeutic strategy for SCI. Heme oxygenase 1(HO-1) regulates the close dynamic crosstalk between oxidative stress and inflammatory responses. This investigation aimed to study the molecular pathways by which HO-1 regulates the inflammatory response of microglia.
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