Tian R, Wu YX, Guo JY, Chen XZ, Tang JF, Zhou CF. Letter to the Editor: Natural product intervention in metabolic dysfunction-associated steatotic liver disease: From allyl isothiocyanate to signaling networks. World J Hepatol 2026; 18(8): 117382 [DOI: 10.4254/wjh.117382]
Corresponding Author of This Article
Ce-Fan Zhou, PhD, Professor, School of Life and Health Sciences, Institute of Biomedical Research, National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, No. 28 Nanli Road, Wuhan 430068, Hubei Province, China. cefan@hbut.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
letter
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Hepatol. Aug 27, 2026; 18(8): 117382 Published online Aug 27, 2026. doi: 10.4254/wjh.117382
Letter to the Editor: Natural product intervention in metabolic dysfunction-associated steatotic liver disease: From allyl isothiocyanate to signaling networks
Rui Tian, Jie-Yu Guo, Jing-Feng Tang, Ce-Fan Zhou, School of Life and Health Sciences, Institute of Biomedical Research, National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, Hubei Province, China
Rui Tian, College of Biological and Food Engineering, Hubei Minzu University, Enshi 445000, Hubei Province, China
Yi-Xin Wu, School of Life and Health Sciences, Hubei University of Technology, Wuhan 430068, Hubei Province, China
Xing-Zhen Chen, Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton AB T6G 2R3, Canada
Author contributions: Tian R prepared the original draft; Zhou CF contributed to the conceptualization, writing, review, and editing of the manuscript; Tian R, Wu YX, Zhou CF, and Tang JF collaboratively drafted the manuscript; Guo JY and Chen XZ provided some valuable opinions, and all authors have reviewed and approved the final version of the manuscript.
AI contribution statement: DeepL software was used for language polishing. The main text of the manuscript was not generated by AI. We did not use any AI tool to participate in the study design or interpretation of the results. No images in the manuscript were generated by AI.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Ce-Fan Zhou, PhD, Professor, School of Life and Health Sciences, Institute of Biomedical Research, National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, No. 28 Nanli Road, Wuhan 430068, Hubei Province, China. cefan@hbut.edu.cn
Received: December 8, 2025 Revised: December 25, 2025 Accepted: February 5, 2026 Published online: August 27, 2026 Processing time: 255 Days and 18.6 Hours
Abstract
The pursuit of effective therapeutic agents against metabolic dysfunction-associated steatotic liver disease continues, with natural products offering promise due to their multi-targeting capabilities. A study published in the World Journal of Hepatology by Gao et al demonstrates that allyl isothiocyanate (AITC) alleviates hepatic steatosis and insulin resistance by upregulating the hepatic vitamin D receptor (VDR), which activates the hepatocyte nuclear factor 4 alpha/microsomal triglyceride transfer protein/apolipoprotein B axis to promote lipid export and β-oxidation while suppressing lipogenesis. While compelling, this VDR-centric model exists in isolation, lacking integration with other known AITC targets like the sirtuin 1/AMP-activated protein kinase axis. Furthermore, although the experimental model provides insightful data, it relies exclusively on in vitro studies, awaiting validation in vivo and direct genetic evidence from VDR knockout models to solidify the causal relationship. This commentary aims to elucidate the multifaceted mechanisms of AITC against metabolic dysfunction-associated steatotic liver disease, underscoring its systemic effects on lipid metabolism, insulin sensitivity, and hepatocyte transcriptional reprogramming, which collectively provide a foundation for developing precise, safe, and sustainable therapeutic strategies.
Core Tip: This comment highlights that allyl isothiocyanate (AITC) exemplifies the principle of multi-target natural product therapy for metabolic dysfunction-associated steatotic liver disease. In addition to the novel vitamin D receptor/hepatocyte nuclear factor 4 alpha pathway identified by Gao et al, we integrate this axis with established AITC targets, such as sirtuin 1/AMP-activated protein kinase and nuclear factor erythroid 2-related factor 2, to construct a multi-signaling network. This network collectively reprograms lipid metabolism, insulin sensitivity, and oxidative stress. Future research must validate this integrative mechanism in vivo and leverage systems biology to advance AITC as a precise, network-based therapeutic strategy.
