RT Journal Article
SR Electronic
T1 Baicalin Promotes CNS Remyelination via PPARγ Signal Pathway
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e1142
DO 10.1212/NXI.0000000000001142
VO 9
IS 2
A1 Ai, Ruo-Song
A1 Xing, Kun
A1 Deng, Xin
A1 Han, Juan-Juan
A1 Hao, Dong-Xia
A1 Qi, Wen-Hui
A1 Han, Bing
A1 Yang, Ya-Na
A1 Li, Xing
A1 Zhang, Yuan
YR 2022
UL http://nn.neurology.org/content/9/2/e1142.abstract
AB Background and Objectives 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.Methods 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.Results 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.Discussion 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.APC=adenomatous polyposis coli; BA=baicalin; CGZ=ciglitazone; CPZ=cuprizone; EAE=experimental autoimmune encephalomyelitis; GFAP=glial fibrillary acidic protein; IBA1=ionized calcium binding adapter molecule 1; LFB=Luxol fast blue; MBP=myelin basic protein; MS=multiple sclerosis; NC=naïve chow; NFH=neurofilament H; NG2=chondroitin sulfate proteoglycan 2; OLGs=oligodendrocytes; Olig2=oligodendrocyte transcription factor 2; OPCs=oligodendrocyte precursor cells; PBS=phosphate-buffered saline; PDGFR α=platelet-derived growth factor receptor α; PEI=polysciences; PGZ=pioglitazone; PPARγ=peroxisome proliferator-activated receptor γ; PPARγ+/-=PPARγ deficient heterozygous; PPRE=peroxisome proliferator element