Baicalin Promotes CNS Remyelination via PPARγ Signal Pathway

• Published in: Neurology : neuroimmunology & neuroinflammation 2022-03, Vol.9 (2)
• Main Authors: Ai, Ruo-Song, Xing, Kun, Deng, Xin, Han, Juan-Juan, Hao, Dong-Xia, Qi, Wen-Hui, Han, Bing, Yang, Ya-Na, Li, Xing, Zhang, Yuan
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Demyelinating Diseases - drug therapy; Disease Models, Animal; Flavonoids - pharmacology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Motor Skills Disorders - drug therapy; PPAR gamma - drug effects; Remyelination - drug effects; Signal Transduction - drug effects
• ISSN: 2332-7812; 2332-7812
• DOI: 10.1212/NXI.0000000000001142

Demyelinating diseases in the CNS are characterized by myelin sheath destruction or formation disorder that leads to severe neurologic dysfunction. Remission of such diseases is largely dependent on the differentiation of oligodendrocytes precursor cells (OPCs) into mature myelin-forming OLGs at the demyelinated lesions, which is defined as remyelination. We discover that baicalin (BA), a natural flavonoid, in addition to its well-known antiinflammatory effects, directly stimulates OLG maturation and CNS myelin repair. To investigate the function of BA on CNS remyelination, we develop the complementary in vivo and in vitro models, including physiologic neonatal mouse CNS myelinogenesis model, pathologic cuprizone-induced (CPZ-induced) toxic demyelination model, and postnatal OLG maturation assay. Furthermore, molecular docking, pharmacologic regulation, and transgenic heterozygous mice were used to clarify the target and action of the mechanism of BA on myelin repair promotion. Administration of BA was not only merely effectively enhanced CNS myelinogenesis during postnatal development but also promoted remyelination and reversed the coordination movement disorder in the CPZ-induced toxic demyelination model. Of note, myelin-promoting effects of BA on myelination or regeneration is peroxisome proliferator-activated receptor γ (PPARγ) signaling-dependent. Our work demonstrated that BA promotes myelin production and regeneration by activating the PPARγ signal pathway and also confirmed that BA is an effective natural product for the treatment of demyelinating diseases.