2,3,4′,5-Tetrahydroxystilbene-2-O-β-D-Glucoside (THSG) Activates the Nrf2 Antioxidant Pathway and Attenuates Oxidative Stress-Induced Cell Death in Mouse Cochlear UB/OC-2 Cells

Abstract

Oxidative stress plays a critical role in the pathogenesis of hearing loss, and 2,3,4 ,5-tetrahydroxystilbene-2-O-β-D-glucoside (THSG) exerts antioxidant effects by inhibiting reactive oxygen species (ROS) generation. With the aim of developing new therapeutic strategies for oxidative stress, this study investigated the protective mechanism of THSG in vitro using a normal mouse cochlear cell line (UB/OC-2). The THSG and ascorbic acid have similar free radical scavenger capacities. H 2 O 2 , but not THSG, reduced the UB/OC-2 cell viability. Moreover, H 2 O 2 might induce apoptosis and autophagy by inducing morphological changes, as visualized by microscopy. As evidenced by Western blot analysis and monodansylcadaverine (MDC) staining, THSG might decrease H 2 O 2 -induced autophagy. According to a Western blotting analysis and Annexin V/PI and JC-1 staining, THSG might protect cells from H 2 O 2 -induced apoptosis and stabilize the mitochondrial membrane potential. Furthermore, THSG enhanced the translocation of nucleus factor erythroid 2-related factor 2 (Nrf2) into the nucleus and increased the mRNA and protein expression of antioxidant/detoxifying enzymes under H 2 O 2 -induced oxidative stress conditions. Collectively, our findings demonstrate that THSG, as a scavenging agent, can directly attenuate free radicals and upregulate antioxidant/detoxifying enzymes to protect against oxidative damage and show that THSG protects UB/OC-2 cells from H 2 O 2 -induced autophagy and apoptosis in vitro.

Otoprotective Effect of 2,3,4′,5-Tetrahydroxystilbene-2-O-β-d-Glucoside on Gentamicin-Induced Apoptosis in Mouse Cochlear UB/OC-2 Cells

“…It has also been shown that THSG inhibits glutamate-induced neurotoxicity via suppression of ROS production [43]. Our previous study reported that THSG has free radical scavengers and activates the Nrf2 signaling pathway to mitigate H 2 O 2 -induced ototoxicity [31]. Here, this study demonstrated that THSG suppressed gentamicin-induced ototoxicity by inhibiting ROS production and activating the antioxidant enzyme, SOD (Figure 2).…”

“…In our previous report, no effect on the survival of UB/OC-2 cells treated with THSG at different concentrations (5–40 μM) for 48 h was seen [ 31 ]. To further investigate whether THSG protects gentamicin-treated UB/OC-2 cells from oxidative stress, the levels of ROS were measured by flow cytometry using the indicator dye 2′,7′-dichlorofluorescein diacetate (DCFDA).…”

“…There are few immortalized cell lines derived from the auditory sensory organ such as the House Ear Institute-Organ of Corti 1 (HEI-OC1), University of Bristol/Organ of Corti-1 (UB-OC-1) and UB/OC-2 cells. The cell line UB/OC-2, a conditionally immortalized mouse cochlear cell line derived from E13 embryos [32,33], has been used to study hereditary hearing loss [34], cell differentiation [35], ototoxicity [36] and otoprotection [31].…”

A Review of Pharmacology, Toxicity and Pharmacokinetics of 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-Glucoside

“…Decreasing the expression of Beclin-1 and LC3-II in autophagy pathways AD-like APP transgenic mice 120, 240 μM/kg Antagonizing the effects of amyloid plaques or inhibiting the formation of amyloid plaques directly reducing the cell damage caused by ROS and electrophilic substances, which maintains the physiological balance of oxidation-antioxidation in the body (Stępkowski and Kruszewski, 2011;Bellezza et al, 2018). In H 2 O 2 -induced oxidative stress of UB/OC-2 cells, TSG (5, 10, 20, 40 μM) showed a strong ability of antioxidant stress by increasing the level of antioxidant/detoxification enzymes such as heme oxygenase 1 (HO-1), NQO1, glutathione-s-transferase (GST), and UGT, as well as inhibiting the excessive production of ROS, apoptosis, and autophagy, which was attributed to the activation of the Nrf2 pathway (Wu et al, 2020). These results suggest that TSG-mediated activation of the Nrf2 signaling pathway may be an important mechanism of enhancing endogenous antioxidant defense system.…”

Plant-Derived Compounds as Promising Therapeutics for Vitiligo

“…Moldenke ( He et al, 2015 ). Numerous studies have found that THSG exerts antioxidant effects by protecting cells from oxidative damage caused by H 2 O 2 through increasing SOD activity, reducing MDA content, and inhibiting ROS production ( Yang et al, 2014 ; Wu et al, 2020 ). In hairless skin model, the extract of Reynoutria multiflora could up regulate SOD in a dose-dependent manner, thereby reducing UVB-induced oxidative damage, suggesting that the extract of Reynoutria multiflora contains anti skin photoaging agent ( Hwang et al, 2006 ).…”