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

Ya-ling Zhang; Yuan Qu; Huan-huan Song; Guo Cheng; Fen Lu; Ting-ting Cui; Ye Gong; Xiao-li Ding; Yang Yang; Qian Zhang; Lu-ting Yang; Ya-ping Yan

Biomedicine & Pharmacotherapy (Sep 2024)

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

Ya-ling Zhang,
Yuan Qu,
Huan-huan Song,
Guo Cheng,
Fen Lu,
Ting-ting Cui,
Ye Gong,
Xiao-li Ding,
Yang Yang,
Qian Zhang,
Lu-ting Yang,
Ya-ping Yan

Affiliations

Ya-ling Zhang: 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; Corresponding authors at: College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi 710119, China.
Yuan Qu: 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
Huan-huan Song: 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
Guo Cheng: 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
Fen Lu: 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
Ting-ting Cui: 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
Ye Gong: 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
Xiao-li Ding: 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
Yang Yang: 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
Qian Zhang: 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
Lu-ting Yang: 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
Ya-ping Yan: 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; Corresponding authors at: College of Life Sciences, Shaanxi Normal University, Xi’an, Shaanxi 710119, China.

Journal volume & issue: Vol. 178
p. 117188

Abstract

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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.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

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