Ethanol causes non-communicable disease through activation of NLRP3 inflammasome: a review on mechanism of action and potential interventions.

Abstract

Background: Ethanol exposure has been suggested to be implicated in the initiation and progression of several non-communicable diseases (NCD), including neurological disorders, diabetes mellitus, alcoholic liver disease, gastric injury, pancreatitis, and atherosclerosis. Recent findings show that the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is involved in the progression of ethanol-induced NCDs.Objective: The aim of this review was to summarize the research progress on NCDs associated with the action of the NLRP3 inflammasome by ethanol and potential interventions, with a specific focus on preclinical literature.Methods: A literature search was conducted on PubMed using the keywords "[ethanol] and [NLRP3]" up until January 2023. Articles describing cases of NCDs caused by ethanol and associated with the NLRP3 inflammasome were included.Results: After removing duplicates, 35 articles were included in this review. These studies, mostly conducted in animals or in vitro, provide evidence that ethanol can contribute to the development of NCDs, such as neurological disorders, alcoholic liver disease, gastric injury, pancreatitis, and atherosclerosis, by activating the NLRP3 inflammasome. Ethanol exposure primarily triggers NLRP3 inflammasome activation by influencing the TRL/NF-κB, ROS-TXNIP-NLRP3 and P2X7 receptor (P2X7R) signaling pathways. Several natural extracts and compounds have been found to alleviate NCDs caused by ethanol consumption by inhibiting the activation of the NLRP3 inflammasome.Conclusion: Preclinical research supports a role for ethanol-induced NLRP3 inflammasome in the development of NCDs. However, the clinical relevance remains uncertain in the relative absence of clinical studies.