Effects of Bu Shen Yi sui capsule on NogoA/NgR and its signaling pathways RhoA/ROCK in mice with experimental autoimmune encephalomyelitis

Ling Fang,Tao Yang,Fang Qi,Yongqiang Wang,Qiuxia Zhang,Zhenzhen Chen,Yongping Fan,Nan Zhang,Kangning Li,Qi Zheng,Junling Li,Hui Zhao,Peiyuan Zhao,Lei Wang,Yuanyuan Zhao

doi:10.1186/s12906-017-1847-4

Abstract

BackgroundAxon growth inhibitory factors NogoA/Nogo receptor (NgR) and its signaling pathways RhoA/Rho kinase (ROCK) play a critical role in the repair of nerve damage in multiple sclerosis (MS). Bu Shen Yi Sui Capsule (BSYSC) is an effective Chinese formula utilized to treat MS in clinical setting and noted for its potent neuroprotective effects. In this study, we focus on the effects of BSYSC on promoting nerve repair and the underlying mechanisms in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS.MethodsThe EAE mouse model was induced by injecting subcutaneously with myelin oligodendrocyte glycoprotein (MOG) 35–55 supplemented with pertussis toxin. BSYSC was orally administrated at dose of 3.0 g/kg once a day for 40 days. The levels of protein gene product (PGP) 9.5, p-Tau, growth associated protein (GAP) -43, KI67 and Nestin in the brain or spinal cord on 20 and 40 day post-induction (dpi) were detected via immunofluorescence and Western blot analysis. Furthermore, NogoA/NgR and RhoA/ROCK signaling molecules were studied by qRT-PCR and Western blot analysis.ResultsTwenty or 40 days of treatment with BSYSC increased markedly PGP9.5 and GAP-43 levels, reduced p-Tau in the brain or spinal cord of mice with EAE. In addition, BSYSC elevated significantly the expression of KI67 and Nestin in the spinal cord 40 dpi. Further study showed that the activation of NogoA/NgR and RhoA/ROCK were suppressed by the presence of BSYSC.ConclusionsBSYSC could attenuate axonal injury and promote repair of axonal damage in EAE mice in part through the down-regulation of NogoA/NgR and RhoA/ROCK signaling pathways.

Highlights

Axon growth inhibitory factors NogoA/Nogo receptor (NgR) and its signaling pathways RhoA/ Rho kinase (ROCK) play a critical role in the repair of nerve damage in multiple sclerosis (MS)
Effects of Bu Shen Yi Sui Capsule (BSYSC) on the protein expression of PGP9.5 in EAE mice IF analysis showed that PGP9.5 protein expression in the brain and spinal cord 20 and 40 dpi was reduced significantly in MO mice as compared with the NC mice (p < 0.01)
The increased PGP9.5 in the spinal cord 20 dpi was shown in both Prednisone acetate (PA) and BSYSC mice as compared with the MO mice (p < 0.05, Fig. 1c)

Summary

Introduction

Axon growth inhibitory factors NogoA/Nogo receptor (NgR) and its signaling pathways RhoA/ Rho kinase (ROCK) play a critical role in the repair of nerve damage in multiple sclerosis (MS). The research found that axon growth inhibitory factors play an important role in the failure of axonal regeneration The inhibitors such as NogoA, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp) bind to a common Nogo-66 receptor (NgR) [10]. Each of the inhibitors interacts in NgR and its co-receptors to transduce the inhibitory signal into neurons [11], activating guanosine triphosphatase (GTPase), increasing the activity of the neuronal cytoskeleton regulatory factor RhoA, resulting in neuronal growth cone collapse and inhibiting the extension and regeneration of axons [12,13,14,15]

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