Polydatin Protects Rat Liver against Ethanol‐Induced Injury: Involvement of CYP2E1/ROS/Nrf2 and TLR4/NF‐κB p65 Pathway

Abstract

Excessive alcohol consumption leads to serious liver injury, associating with oxidative stress and inflammatory response. Previous study has demonstrated that polydatin (PD) exerted antioxidant and anti-inflammatory effects and attenuated ethanol-induced liver damage, but the research remained insufficient. Hence, this experiment aimed to evaluate the hepatoprotective effect and potential mechanisms of PD on ethanol-induced hepatotoxicity. Our results showed that PD pretreatment dramatically decreased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in the serum, suppressed the malonaldehyde (MDA) and triglyceride (TG) content and the production of reactive oxygen species (ROS), and enhanced the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), andalcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH), paralleled by an improvement of histopathology alterations. The protective effect of PD against oxidative stress was probably associated with downregulation of cytochrome P450 2E1 (CYP2E1) and upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its target gene haem oxygenase-1 (HO-1). Moreover, PD inhibited the release of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) via downregulating toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) p65. To conclude, PD pretreatment protects against ethanol-induced liver injury via suppressing oxidative stress and inflammation.

Polydatin suppresses nucleus pulposus cell senescence, promotes matrix homeostasis and attenuates intervertebral disc degeneration in rats

“…19 Also, the property of PD on Nrf2 activation has been proved in different diseases models but not IVDD. [20][21][22] In this study, we report that PD exerts properties of antisenescence and anti-ECM catabolism in NPCs treated with TNF-α. Further, we discover that PD decreases the ROS production and protects NPCs from mitochondrial dysfunction induced by TNF-α.…”

“…Similar to RSV structurally, PD possesses multiple pharmacological properties of antioxidation, anti‐inflammation and antitumour . Also, the property of PD on Nrf2 activation has been proved in different diseases models but not IVDD …”

Sophocarpine Attenuates LPS-Induced Liver Injury and Improves Survival of Mice through Suppressing Oxidative Stress, Inflammation, and Apoptosis

“…Meanwhile, sophocarpine obviously upregulated the activity and expression of endogenous antioxidants, such as SOD, CAT, and GSH, suggesting that sophocarpine shows its potential antioxidative by blocking ROS-mediated signaling. As an essential sensor of redox status in ROS process, cellular Nrf2 often binds to the cytoskeletal-anchoring protein under normal conditions [ 39 ]. As the main contributor, CYP2E always promotes the production of ROS in liver injury and ethanol-induced oxidative stress [ 11 ].…”

Anti-inflammatory and hepatoprotective effects of exopolysaccharides isolated from Pleurotus geesteranus on alcohol-induced liver injury

“…Inflammation is another representative pathological mechanism that is responsible for alcohol-induced liver injury 10 . Oxidative stress can induce the expression of pro-inflammatory cytokines to facilitate inflammatory responses, which aggravates liver injury 43 .…”

“…Cytochrome P450 enzymes, especially the CYP2E1 isoform, represent a secondary pathway responsible for alcohol removal at high concentrations. Breakdown of acetaldehyde by CYP2E1 and ALDH in the mitochondria generates reactive oxygen/nitrogen species, which disturbs the redox homeostasis and causes oxidative stress 10 , 11 . These free radicals can increase lipid peroxidation by reacting with cellular unsaturated lipids, leading to hepatocyte apoptosis and necrosis, which ultimately results in liver injury 12 .…”