Isoliquiritigenin alleviates experimental autoimmune encephalomyelitis by modulating inflammatory and neuroprotective reactive astrocytes.

Biomed Pharmacother

Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, Xi'an, Shaanxi 710119, China; National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, Xi'an, Shaanxi 710119, China; College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi 710119, China. Electronic address:

Published: September 2024

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2024.117188DOI Listing

Publication Analysis

Top Keywords

reactive astrocytes
24
neuroprotective reactive
16
experimental autoimmune
8
autoimmune encephalomyelitis
8
inflammatory neuroprotective
8
ilg
8
additionally ilg
8
inhibits inflammatory
8
inflammatory reactive
8
astrocytes promotes
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!