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

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.

Inhibition of p38 ameliorates axonal loss with modulation of autophagy in TNF-induced optic nerve damage

“…Consistent with our previous studies [14,15] and compared with the control group (Fig. 1a), the TNF group showed apparent degenerative findings in the optic nerve (Fig.…”

“…One week after intravitreal injection, optic nerves (4 mm in length) were collected, homogenized, and centrifuged at 15,000 × g for 15 min at 4 °C as described previously [15]. Protein concentrations in supernatants were measured.…”

“…Our previous reports showed that autophagy induction leads to axonal protection in the TNF-induced optic nerve degenerative model [13,14]. We recently reported that Akebia Saponin D (ASD), which is also known as an autophagy inducer exerts axonal protection in the TNF-induced optic nerve degeneration model [15]. That study also found that phosphorylated-p38 (p-p38) exists in optic nerve axons and is upregulated by TNF, and that this upregulation was prevented by ASD [15].…”

“…We recently reported that Akebia Saponin D (ASD), which is also known as an autophagy inducer exerts axonal protection in the TNF-induced optic nerve degeneration model [15]. That study also found that phosphorylated-p38 (p-p38) exists in optic nerve axons and is upregulated by TNF, and that this upregulation was prevented by ASD [15]. However, a recent study demonstrated that resveratrol, which is also known as an autophagy inducer ameliorated the high glucose-induced oxidative damage in human lens epithelial cells by promoting autophagy through the upregulation of p-p38 [16].…”

Asperosaponin VI Ameliorates The CMS-Induced Depressive-Like Behaviors By Inducing A Neuroprotective Microglial Phenotype To Restore Hippocampal Synaptic Plasticity Via PPAR-γ Pathway

“…Here, using a classical animal model of depression, we showed that asperosaponin VI induces a PPAR-γ-dependent neuroprotective microglial phenotype that mitigates depression-like behaviors induced by CMS, which is associated with restoration of hippocampal synaptic function. Our work extends the list of conditions where asperosaponin VI can exert therapeutic antiin ammatory and neuroprotective effects in the brain, a list that already includes Alzheimer's disease and optic nerve damage [19,24]. Depression usually manifests as diverse debilitating symptoms, including hopelessness and anhedonia [25].…”