Letter to the Editor
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Oct 27, 2024; 16(10): 1208-1212
Published online Oct 27, 2024. doi: 10.4254/wjh.v16.i10.1208
Suppression of hepatic steatosis in non-alcoholic steatohepatitis model by modified Xiaoyao San formula: Evidence, mechanisms and perspective
Nabil Eid, Payal Bhatnagar, Li-Li Chan, Marina Garcia-Macia
Nabil Eid, Department of Anatomy, Division of Human Biology, School of Medicine, IMU University, Kuala Lumpur 57000, Malaysia
Payal Bhatnagar, Department of Pharmaceutical Technology, School of pharmacy, IMU University, Kuala Lumpur 57000, Malaysia
Li-Li Chan, Department of Pathology and Pharmacology, School of Medicine, IMU University, Kuala Lumpur 57000, Malaysia
Marina Garcia-Macia, Institute of Functional Biology and Genomics, Department of Biochemistry and Molecular Biology, University of Salamanca, Salamanca 37007, Spain
Author contributions: Eid N wrote and approved the final draft of the manuscript; Bhatnagar P designed the figure; Chan LL revised the text and the artwork; Garcia-Marina M revised the manuscript; All authors have read and approved the final manuscript.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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: Nabil Eid, PhD, Academic Editor, Affiliate Associate Professor, Department of Anatomy, Division of Human Biology, School of Medicine, IMU University, Bukit Jalil, Kuala Lumpur 57000, Malaysia. nabilsaleheid@imu.edu.my
Received: July 10, 2024
Revised: September 24, 2024
Accepted: October 11, 2024
Published online: October 27, 2024
Processing time: 102 Days and 21.5 Hours
Abstract

In this letter, we comment on a recent publication by Mei et al, in the World Journal of Hepatology, investigating the hepatoprotective effects of the modified Xiaoyao San (MXS) formula in a male rat model of non-alcoholic steatohepatitis (NASH). The authors found that MXS treatment mitigated hepatic steatosis and inflammation in the NASH model, as evidenced by the reduction in lipid droplets (LDs), fibrosis markers and lipogenic factors. Interestingly, these hepatoprotective effects were associated with androgen upregulation (based on metabolomics analysis of male steroid hormone metabolites), adenosine 5’-monophosphate-activated protein kinase (AMPK) activation, and restoration of phosphatase and tensin homolog (PTEN) expression. However, the authors did not clearly discuss the relationships between MXS-induced hepatic steatosis reduction in the NASH model, and androgen upregulation, AMPK activation, and restoration of PTEN expression. This editorial emphasizes the reported mechanisms and explains how they act or interact with each other to reduce hepatic steatosis and inflammation in the NASH model. As a perspective, we propose additional mechanisms (such as autophagy/lipophagy activation in hepatocytes) for the clearance of LDs and suppression of hepatic steatosis by MXS in the NASH model. A proper understanding of the mechanisms of MXS-induced reduction of hepatic steatosis might help in the treatment of NASH and related diseases.

Keywords: Steatosis; Liver; Xiaoyao San; Inflammation; Androgen; Adenosine 5’-monophosphate-activated protein kinase; Phosphatase and tensin homolog; Autophagy; Lipophagy; Alpha smooth muscle actin

Core Tip: Modified Xiaoyao San (MXS) formula has hepato-protective effects in a male rat model of non-alcoholic steatohepatitis (NASH) via suppression of steatosis and inflammation. These protective effects are related to several mechanisms, including the regulation of sex hormone metabolism, androgen upregulation, adenosine 5’-monophosphate-activated protein kinase activation, and enhanced phosphatase and tensin homolog expression. A deeper understanding of the mechanisms behind MXS-induced reduction of hepatic steatosis could assist in the treatment of NASH and related diseases.