Neuroprotective Effects of Dehydroglyasperin C through Activation of Heme Oxygenase-1 in Mouse Hippocampal Cells

Abstract

Licorice, the root of the Glycyrrhiza species ( Glycyrrhiza uralensis Fisher), is known to have antioxidant, anti-inflammatory, antiviral, and antitumor properties. The objective of this study is to explore the neuroprotective effect of dehydroglyasperin C (DGC) against glutamate-induced oxidative stress in mouse hippocampal HT22 cells. DGC significantly reduced cytotoxicity and reactive oxygen species (ROS) generation induced by glutamate in HT22 cells, whereas DGC did not restore glutathione depletion caused by glutamate. In addition, it was further investigated whether DGC affected the expression of heme oxygenase (HO)-1, one of the major cellular antioxidant defense systems, and it was found that DGC dose-dependently increased HO-1 expression. DGC-mediated cytoprotection of HT22 neuronal cells from glutamate insult was abrogated by either HO-1 inhibitor (Tin protoporphyrin, SnPP) or AKT inhibitor (LY294002). In conclusion, the present results demonstrate for the first time that DGC protects neuronal cells against glutamate-induced oxidative injury through the induction of HO-1 expression, which is, in turn, activated maybe through Nrf2-Keap1 and PI3K/AKT signaling pathways.

The anti-inflammatory activity of licorice, a widely used Chinese herb

“…DGC, DGD and ISOA all showed strong ferric reducing activities and effectively scavenged DPPH, ABTS þ and singlet oxygen radicals (Kim HJ et al 2012b). Furthermore, DGC increased the expression of haemeoxygenase-1 and MAPK phosphatase-1, suppressed the inflammation-mediated neurodegeneration, production of TNF-a, NO, ROS, NF-jB and phosphorylation of p38 MAPKs, ERK1/2, IjB-a and p65 (Kim HJ et al, 2012a;. GLD significantly inhibited NO and IL-1b release (Thiyagarajan et al 2011), attenuated colonic inflammation in mice with dextran sulphate sodiuminduced colitis (Kwon et al 2008), and decreased the iNOS mRNA expression under high-glucose levels, which indicated that GLD could be applied to diabetes-related vascular dysfunction (Yehuda et al 2015).…”

Pharmacological Effects ofGlycyrrhizaspp. and Its Bioactive Constituents: Update and Review

“…Dehydroglyasperin C, as an active component of G. uralensis, can produce neuroprotective effects against glutamate-induced oxidative stress in mouse hippocampal HT22 cells by inducing heme oxygenase (HO)-1 expression; NF (erythroid-derived 2)-like 2 and the phosphoinositide-3-kinase/AKT signaling pathway may be involved in activation of HO-1 (Kim et al, 2012a). Kawakami et al (2010) reported that glycyrrhizin and 18β-glycyrrhetinic acid (10 À7 -10 À4 M) ameliorate thiamine deficiency-induced dysfunction of glutamate uptake in astrocytes and that the two compounds could inhibit protein kinase C activity.…”

Grape Peel Extract and Resveratrol Inhibit Wrinkle Formation in Mice Model Through Activation of Nrf2/HO‐1 Signaling Pathway

“…As activation of Nrf2‐mediated antioxidant enzymes could facilitate protection to epidermal cells in skin from oxidative damage (Kim et al., ; Linker et al., ; Romeo et al., ; Zhang et al., ), we hypothesized that resveratrol or resveratrol‐enriched grape peel extract could attenuate skin wrinkle formation caused by UVB‐mediated ROS production. The involvement of Nrf2 signaling pathway in resveratrol‐mediated protection of skin has been reported on cultured cells in vitro (Cao et al., ; Chan et al., ; Hirota et al., ; Liu et al., ), but to our knowledge it has never been successfully demonstrated in animal model.…”