| Objective: Multiple sclerosis(MS) is an inflammatory demyelinating disease of the central nervous system. It is the most common autoimmunol disabling neurological disease in young adults. The pathological hallmarks of MS include the destruction of myelin, axonal damage and complete axonal transaction. Therefore, demyelination protection is a key factor in MS therapy. According to the theory of traditional Chinese medicine, Epimedium can nourish “the kidneys”, replenish ‘yang’ and strengthen the bones, and sometimes has an indication for the treatment of impotence. Can traditional Chinese medicine protect the demyelination? In the present study, we will research the effect of epimedium flavonoids(EF), icariin(ICA), main components extracted from epimedium sagittatum, on myelin sheath damage in cuprizone(CPZ)-induced toxic demyelinating model in C57BL/6 mice. Furthermore, we also explore the possible mechanisms underlying the protective effect.Methods: Female C57BL/6J mice were fed with chow containing 0.2% CPZ(bis-cycloexanone oxaldihydrazone) to induce the white matter demyelination such as corpus callosum. Mice were fed with special chow for 6 weeks to induce a reversible acute animal model, while 12 weeks to induce unreversible chronic model. EF or ICA were treated before demyelination for 3~4 weeks.In order to evaluate the effects of EF or ICA on myelin regeneration, after mice were fed with chow containing 0.2% CPZ for 5 weeks, mice in CPZ model or drugs therapy groups were fed with regular chow for another 3 weeks, whether EF or ICA could promote myelin regeneration were detected.In acute animal model, mice were divided into the following six gruops: normal control group(Ctrl); CPZ model group; CPZ+ICA 25 mg/kg group; CPZ+ICA 50mg/kg group; EF 50 and 100 mg/kg groups. In chronic animal model, mice were divided into the following four gruops: normal control group; CPZ model group; CPZ+ICA 25 mg/kg group; CPZ+ICA 50 mg/kg group. In myelin regeneration aniamal model,mice were divided into the following six gruops: normal control group; vehicle CMC-Na group; CPZ model group; ICA 6.25, 12.5 and 25 mg/kg group. EF or ICA were received intragastricly on a daily basis. Body weight of each animal was recorded everyday. Myelin demyelination were evaluated by Oil Red O staining, LFB-PAS staining, and western blotting. Expressions of MBP, mature oligodendrocytes,oligodendrocyte precursor cells, IGF-1 and BDNF were evaluated by immunohistochemical staining. Microglia, astrocytes and its secreted factors were measured by immunofluorescence staining.Results:1. CPZ-induced demyelination animal model were established successfully in female C57/BL6 J mice. EF administration could prevent the breakdown of myelin in corpus callosum. Our study suggests that decreased OL loss and oligodendrocyte precursor cell accumulation, upregulated IGF-1 expression may play a role in this protection of EF.2. In CPZ-induced acute or chronic animal model, ICA could prevent against myelin demyelination effectively. The mechanisms underlying ICA effect may relate to the promotion of OPCs to OLs differentiation and OLs mature, upregulation of neurotrohpic factor such as BDNF.3. In addition, ICA could also promote myelin remyelination, inhibition of microglia activation may play a key role in its mechanism.Conclusion:1.Both EF and ICA could prevent myelin demylination induced by CPZ in acute and chronic animal model. It may relate to decrease the number of OPCs, increase mature OLs and promote expressions of neurotrophic factors such as IGF-1 and BDNF.2. ICA, monomer component extracted from epimedium sagittatum, also has effect on promotion of myelin repairation. Regulation the activation of microglia and astrocytes may involve in the ICA effect on promotion of myelin remyelination... |
PDF Full Text Request