Akebia Saponin D prevents axonal loss against TNF-induced optic nerve damage with autophagy modulation
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ORIGINAL ARTICLE
Akebia Saponin D prevents axonal loss against TNF-induced optic nerve damage with autophagy modulation Kana Sase1 · Chihiro Tsukahara1,2 · Naoki Fujita1,2 · Ibuki Arizono1,2 · Hitoshi Takagi1 · Yasushi Kitaoka2 Received: 18 June 2020 / Accepted: 16 November 2020 © The Author(s) 2020
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. Keywords TNF · Optic nerve · Axon · p62 · Autophagy · p38
Introduction 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 [1–4]. Several studies have demonstrated the relationship between autophagy and glaucoma, however, its role related to retinal ganglion cells (RGCs) and the optic nerve remains controversial [5–8]. Glaucoma is a neurodegenerative disease in which RGCs and their axons progressively degenerate. Though a protective role of autophagy has been reported in an experimental hypertensive glaucoma model [8], a detrimental role of autophagy has been reported in the hypertensive glaucoma model [9]. Our previous studies showed that enhanced * Kana Sase miukana0318@marianna‑u.ac.jp 1
Department of Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
Department of Molecular Neuroscience, St. Marianna University Graduate School of Medicine, 2‑16‑1 Sugao, Miyamae‑ku, Kawasaki, Kanagawa 216‑8511, Japan
2
autophagy flux is involved in axonal protection against in the hypertensive glaucoma model and tumor necrosis factor (TNF)-induced optic nerve degeneration model [10, 11]. Akebia saponin D (ASD) is extracted from herbal medicine Dipsacus asper Wall. A previous report showed that ASD increased autophagic flux in the mice hepatic steatosis model [12]. In neuronal cells, it
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