Abstract

Hepatic encephalopathy is a common complication in patients with liver cirrhosis and portosystemic shunting. Patients with hepatic encephalopathy present a variety of clinical features, including neuropsychiatric manifestations, cognitive dysfunction, impaired gut barrier function, hyperammonemia, and chronic neuroinflammation. These pathogeneses have been linked to various factors, including ammonia-induced oxidative stress, neuronal cell death, alterations in the gut microbiome, astrocyte swelling, and blood-brain barrier disruptions. Many researchers have focused on identifying novel therapeutics and prebiotics in the hope of improving the treatment of these conditions. Resveratrol is a natural polyphenic compound and is known to exert several pharmacological effects, including antioxidant, anti-inflammatory, and neuroprotective activities. Recent studies suggest that resveratrol contributes to improving the neuropathogenic effects of liver failure. Here, we review the current evidence describing resveratrol’s effects in neuropathogenesis and its impact on the gut-liver axis relating to hepatic encephalopathy. We highlight the hypothesis that resveratrol exerts diverse effects in hepatic encephalopathy and suggest that these effects are likely mediated by changes to the gut microbiota, brain edema, and neuroinflammation.

Highlights

  • We reviewed the therapeutic potential of resveratrol in the treatment of hepatic encephalopathy (HE), focusing on gut microbiota, brain edema, and neuroinflammation

  • Our review supports the assertion that resveratrol is beneficial in reducing harmful gut microbes and maintaining the gut barrier integrity in response to metabolic imbalances

  • It demonstrates that resveratrol reduces brain edema via the regulation of both water permeability in the blood-brain barrier (BBB)

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Resveratrol has been reported to exert anti-inflammatory, antiviral, and antioxidant effects in cells and has been shown to reduce oxidative stress-related cell damage [14,15,16]. The resveratrol-mediated activation of the SIRT1 gene induces increased ROS scavenging and improves cognitive function [32,33]. A meta-analysis study suggested that resveratrol has no significant effect on cognitive function [34], another meta-analysis study indicated that oral resveratrol treatment improves some cognitive performances in subjects [35]. Based on these reports, the effect of resveratrol on cognitive improvement has so far been controversial [36]. We summarize the therapeutic potential of resveratrol in HE from several points of view, including its impact on the microbiota, brain edema, and inflammation

Resveratrol and HE
Resveratrol and the Microbiome in HE
Resveratrol and Brain Edema in HE
Resveratrol and Ammonia-Induced Neuroinflammation in HE
Findings
Conclusions

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