Minireviews
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 28, 2023; 29(12): 1824-1837
Published online Mar 28, 2023. doi: 10.3748/wjg.v29.i12.1824
New uses for an old remedy: Digoxin as a potential treatment for steatohepatitis and other disorders
Fatima Jamshed, Farzaneh Dashti, Xinshou Ouyang, Wajahat Z Mehal, Bubu A Banini
Fatima Jamshed, Farzaneh Dashti, Xinshou Ouyang, Wajahat Z Mehal, Bubu A Banini, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT 06510, United States
Fatima Jamshed, Griffin Hospital-Yale University, Derby, CT 06418, United States
Wajahat Z Mehal, West Haven Veterans Medical Center, West Haven, CT 06516, United States
Author contributions: The manuscript was outlined and proposed by Banini BA; The literature search, critical assessment of the literature, and writing of the manuscript were performed by Jamshed F, Dashti F, Ouyang X, Mehal WZ, and Banini BA; All authors discussed the manuscript and reviewed and edited the final version.
Supported by NIH UO1 (to Mehal WZ), No. 5U01AA026962-02.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Bubu A Banini, MD, PhD, Assistant Professor, Section of Digestive Diseases, Yale School of Medicine, 40 Temple St, Suite 1A, New Haven, CT 06510, United States. bubu.banini@yale.edu
Received: November 19, 2022
Peer-review started: November 19, 2022
First decision: December 10, 2022
Revised: January 12, 2023
Accepted: March 14, 2023
Article in press: March 14, 2023
Published online: March 28, 2023
Processing time: 129 Days and 5.7 Hours
Abstract

Repurposing of the widely available and relatively cheap generic cardiac gly-coside digoxin for non-cardiac indications could have a wide-ranging impact on the global burden of several diseases. Over the past several years, there have been significant advances in the study of digoxin pharmacology and its potential non-cardiac clinical applications, including anti-inflammatory, antineoplastic, metabolic, and antimicrobial use. Digoxin holds promise in the treatment of gastrointestinal disease, including nonalcoholic steatohepatitis and alcohol-associated steatohepatitis as well as in obesity, cancer, and treatment of viral infections, among other conditions. In this review, we provide a summary of the clinical uses of digoxin to date and discuss recent research on its emerging applications.

Keywords: Digoxin; Cardiac glycosides; Oxidative stress; Nonalcoholic steatohepatitis; Alcohol-associated steatohepatitis; Sterile inflammation

Core Tip: Digoxin has been used primarily as a cardiac drug for treatment of arrhythmias and heart failure. Preclinical work supports the repurposing of digoxin as therapy for non-cardiac conditions, including alcohol-associated steatohepatitis, nonalcoholic steatohepatitis, obesity and metabolic disorders, autoimmune and inflammatory conditions, malignancy, and viral infections, among others. Here, we provide an overview of findings to date on the potential clinical applications of digoxin and mechanisms of action in steatohepatitis and other non-cardiac disorders. We discuss evidence on the differential action of digoxin at high vs low concentrations and identify areas of further research necessary to harness its promising multifunctional use.