Ginkgolide K induces myelin regeneration by immunoregulation

Abstract

Ginkgolide K (GK), a novel compound isolated from Ginkgo biloba, has shown the neuroprotective capacity In this study, the therapeutic potential and its possible mechanisms of GK for myelin protection were explored through cuprizone (CPZ)-induced demyelination model and MOG-induced encephathogenic cells The mice of CPZ-induced demyelination were treated with GK (20mg/kg/day) for two weeks. Then mice were sacrificed and splenic mononuclear cells (MNCs) and brains were obtained. Immune changes and myelin regeneration were observed by flow cytometry, ELISA, Western blot and etc. MOG-specific encephalopathic cells were treated with GK. Cell viability was detected by MTT in vitro. ELISA and flow cytometry were performed to observe the levels of pro-/anti-inflammation cytokines and the change of immune cell subsets respectively GK reduced behavioral abnormality and effectively protected myelin from damage. CPZ feeding triggered atrophy of the spleen and production of MOG-specific antibody, and this was strongly inhibited by GK treatment. GK prevented the infiltration of T, B cells and macrophages, inhibited IL-1β, IL-6 and TNF-α production in the brain, suppressed the inflammation response of MOG-specific encephalopathic cells. Administration of GK also promoted the proliferation and differentiation of oligodendroglia precursor cells (OPCs) GK showed a potential therapeutic role in CPZ-mediated demyelination. In addition to its inhibition of myelin-specific autoantibody production and immune-regulation, GK may protect a supportive microenvironment for CNS remyelination. (NNSF of China 81473577, Shanxi Scholarship Council of China 2014-7, the 2011 Cultivation Project of SUTCM 2011PY-1. Ma and Xiao are corresponding authors).