Akebia Saponin D prevents axonal loss against TNF-induced optic nerve damage with autophagy modulation

Kana Sase,Yasushi Kitaoka,Ibuki Arizono,Chihiro Tsukahara,Hitoshi Takagi,Naoki Fujita

doi:10.1007/s11033-020-06008-y

Kana Sase, Yasushi Kitaoka + Show 4 more

Open Access

https://doi.org/10.1007/s11033-020-06008-y

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Abstract

Akebia Saponin D (ASD), a triterpenoid saponin, was shown to have protective effects in certain neuronal cells. The purpose of the present study was to investigate the possibility of ASD to prevent tumor necrosis factor (TNF)-induced axonal loss and the ASD modulation of the biologic process of autophagy in optic nerves. Rats were given intravitreal administration of TNF, simultaneous administration of 2, 20, or 200 pmol ASD and TNF, or ASD alone. LC3-II and p62 expression, which is a marker of autophagic flux, and phosphorylated p38 (p-p38) expression in optic nerves were examined by immunoblot analysis. Morphometric analysis revealed a significant ameliorated effect of ASD against TNF-induced optic nerve damage. p62 was significantly increased in the optic nerve in TNF-treated eyes, but this increase was totally prevented by ASD. The ASD alone injection showed significant reduction of p62 levels compared with the PBS-treated control eyes. LC3-II was significantly increased by ASD treatment in the TNF-injected eyes. p-p38 was significantly increased in the optic nerve in TNF-treated eyes, but this increase was completely prevented by ASD. The protective effects of ASD may be associated with enhanced autophagy activation and inhibition of p-p38.

Highlights

Autophagy, a cellular process which includes the degradation of cytoplasmic and axoplasmic components, has been linked to the pathophysiology of certain human diseases, such as neurodegenerative diseases [1,2,3,4]
Immunohistochemical study found abundant p-p38 immunoreactivity in tumor necrosis factor (TNF)-treated group and that some of these immunoreactivities were colocalized with neurofilament immunoreactivity in optic nerve (Fig. 5, upper panel). It seemed that the expression of p-p38 was modest in the TNF + Akebia Saponin D (ASD) group compared to the TNF group (Fig. 5, lower panel). These findings suggested that p-p38 is present in the optic nerve axon, and the expression may be decreased by ASD
Our previous study showed that induction of autophagy is involved in axonal protection against TNF- induced degeneration in the optic nerve [11, 21]

Summary

Introduction

A cellular process which includes the degradation of cytoplasmic and axoplasmic components, has been linked to the pathophysiology of certain human diseases, such as neurodegenerative diseases [1,2,3,4]. Several studies have demonstrated the relationship between autophagy and glaucoma, its role related to retinal ganglion cells (RGCs) and the optic nerve remains controversial [5,6,7,8]. A previous report showed that ASD increased autophagic flux in the mice hepatic steatosis model [12]. Among MAPK, a previous study demonstrated a detrimental role of phosphorylated p38 (p-p38) in RGCs in an optic nerve crush model [16]. A recent study showed that inhibition of p38 resulted in enhanced autophagy induction in a spinal cord injury rat model [17], suggesting a relationship between p38 and autophagy.

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