Resveratrol Attenuates Oxidative Stress-Induced Intestinal Barrier Injury through PI3K/Akt-Mediated Nrf2 Signaling Pathway

Abstract

Oxidative stress is implicated in a wide range of intestinal disorders and closely associated with their pathological processes. Resveratrol (RSV), a plant extract, plays a vital role in protecting various organs in vitro and in vivo. However, the benefits of RSV are controversial, and underlying mechanisms for its antioxidant effects on intestinal epithelial cells remain unclear. In this study, we evaluated the effects of RSV on oxidative stress induced by H2O2 in IPEC-J2 cells. We found that pretreatment with RSV significantly increased cell viability; increased expression levels of tight junction (TJ) proteins (claudin-1, occludin, and ZO-1); improved activities of superoxide dismutase-1 (SOD-1), catalase (CAT), and glutathione peroxidase (GSH-Px); and decreased intracellular reactive oxygen species (ROS) levels and apoptosis induced by H2O2 (P < 0.05). In addition, RSV upregulated Akt phosphorylation, Nrf2 phosphorylation, and expression levels of antioxidant genes HO-1, SOD-1, and CAT in a dose-dependent manner (P < 0.05) under oxidative stress. Knockdown of Nrf2 by short-hairpin RNA (shRNA) abrogated RSV-mediated protection against H2O2-induced apoptosis, RSV-induced increase of TJ protein levels, and antioxidant gene expression (SOD-1, CAT, and GSH-Px) (P < 0.05). Consistent with Nrf2 knockdown, the PI3K/Akt inhibitor LY294002 significantly suppressed RSV-induced Nrf2 phosphorylation and RSV-induced increase of TJ protein levels and antioxidant gene expression under H2O2 treatment (P < 0.05). Collectively, these results demonstrate that RSV can directly protect IPEC-J2 cells against oxidative stress through the PI3K/Akt-mediated Nrf2 signaling pathway, suggesting that RSV may be an effective feed additive against intestinal damage in livestock production.

Resveratrol Improves Bnip3-Related Mitophagy and Attenuates High-Fat-Induced Endothelial Dysfunction

“…At the molecular level, two mechanisms involved in how resveratrol attenuates hyperlipemia-related cardiomyocyte injury have been reported: one is driven by upregulation of antioxidative factors and the other involves downregulation of pro-inflammation cytokines. For example, resveratrol attenuates lipid peroxidation (Jalili et al, 2019) through modulation of several antioxidative signaling pathways such as Nrf2 (Zhuang et al, 2019), Sirt1 (Liu et al, 2019a), Akt/mTOR (Radwan and Karam, 2020), and ERK1/2 (Fathalipour et al, 2019). In addition, the mRNA expression of inflammatory cytokines in diabetic mice are largely inhibited by resveratrol (Xing et al, 2020).…”

Resveratrol decreases cell apoptosis through inhibiting DNA damage in bronchial epithelial cells

“…In the present study, high expression levels of 8-OHdG/8-oxoG were detected, which indicated that the bronchial epithelial cells were damaged. In vitro studies have shown that RES induces the production of antioxidants to reduce the impact of ROS (43)(44)(45). A study on RES indicated that treatment of aged rats with RES can activate Nrf2 and attenuate oxidative stress in endothelial cells.…”

Bungeanum Improves Cognitive Dysfunction and Neurological Deficits in D-Galactose-Induced Aging Mice via Activating PI3K/Akt/Nrf2 Signaling Pathway

“…When oxidative stress or damage increased in aging mammals, Nrf2 knockout mice exhibited severe susceptibility to oxidative damage and decreased expression of Nrf2 , indicating that Nrf2 has neuroprotective effects. In addition, the activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway promotes the translocation of Nrf2 from the cytoplasm to the nucleus to facilitate the transcription of detoxification enzyme and antioxidant enzyme protein gene (Zhuang et al, 2019). Some drugs were reported to activate PI3K/ Akt signaling pathway and promote the transcription of Nrf2 to relieve cognitive impairment and neurological deficits (Liang et al, 2019).…”