Isoliquiritigenin alleviates experimental autoimmune encephalomyelitis by modulating inflammatory and neuroprotective reactive astrocytes - 21/08/24
Abstract |
Multiple sclerosis (MS) is an autoimmune-mediated chronic inflammatory demyelinating disease of the central nervous system (CNS) that poses significant treatment challenges. Currently, it is believed that inflammatory and neuroprotective reactive astrocytes, along with other resident CNS cells and immune cells, contribute to the pathophysiology of MS. In our study, we found that isoliquiritigenin (ILG), a bioactive chalcone compound, significantly reduces the clinical scores of experimental autoimmune encephalomyelitis (EAE) by 44 % (P < 0.05). Additionally, ILG significantly decreases the pathological scores of spinal cord inflammation and demyelination by 61 % and 65 %, respectively (both P < 0.0001). Furthermore, ILG affects the populations of CD4, Th1, Th17, and Treg cells in vivo. More importantly, ILG significantly promotes the activation of astrocytes in EAE (P < 0.0001). Additionally, ILG treatment indirectly inhibits inflammatory reactive astrocytes and promotes neuroprotective reactive astrocytes. It reduces spleen levels of TNFα, IL1α, C1qa, IL1β, and IL17A by 95 % (P < 0.001), 98 % (P < 0.01), 46 % (P < 0.05), 97 % (P < 0.001), and 60 % (P < 0.001), respectively. It also decreases CNS levels of TNFα, IL1α, C1qa, IL1β, and IL17A by 53 % (P < 0.05), 88 % (P < 0.05), 64 % (P < 0.01), 57 % (P < 0.05), and 60 % (P < 0.001), respectively. These results indicate that ILG exerts an immunoregulatory effect by inhibiting the secretion of pro-inflammatory cytokines. Consequently, ILG inhibits inflammatory reactive astrocytes, promotes neuroprotective reactive astrocytes, alleviates inflammation and improves EAE. These findings provide a theoretical basis and support for the application of ILG in the prevention and treatment of MS.
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Highlight |
• | Isoliquiritigenin (ILG) can alleviate clinical symptoms of EAE and decrease spinal cord inflammation and demyelination. |
• | ILG can modulate inflammatory and neuroprotective reactive astrocytes in EAE. |
• | ILG can decrease the content of specific inflammatory cytokines in cell culture supernatants. |
Abbreviations : BBB, CFA, CNS, DAPI, EAE, ELISA, H&E, GFAP, LFB, I.p., LPS, MNCs, MS, MOG35–55, PT, QRT-PCR, S.c., TNF
Keywords : Isoliquiritigenin, Multiple sclerosis, Experimental autoimmune encephalomyelitis, Inflammatory, neuroprotective, Reactive astrocytes
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Vol 178
Article 117188- septembre 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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