Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2025; 31(17): 105438
Published online May 7, 2025. doi: 10.3748/wjg.v31.i17.105438
Bicuculline ameliorates metabolic dysfunction-associated steatotic liver disease by inhibiting the nuclear factor-kappa B pathway and reducing lipid accumulation
Xiao-Mei Wang, Ze Dai, Dai-Jun Lu, Chao-Qun Bao, Nai-Bin Yang, Yu-Ping Zhou
Xiao-Mei Wang, Dai-Jun Lu, Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
Xiao-Mei Wang, Ze Dai, Dai-Jun Lu, Health Science Center, Ningbo University, Ningbo 315211, Zhejiang Province, China
Chao-Qun Bao, Yu-Ping Zhou, Department of Traditional Chinese Medicine, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
Nai-Bin Yang, Department of Hepatology, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
Yu-Ping Zhou, Institute of Digestive Disease of Ningbo University, Ningbo University, Ningbo 315020, Zhejiang Province, China
Yu-Ping Zhou, Ningbo Key Laboratory of Translational Medicine Research on Gastroenterology and Hepatology, Ningbo Key Laboratory, Ningbo 315020, Zhejiang Province, China
Author contributions: Zhou YP designed and coordinated the study; Wang XM, Dai Z, Lu DJ and Bao CQ performed the experiments and acquired and analyzed the data; Wang XM, Dai Z and Yang NB interpreted the data; Wang XM and Lu DJ wrote the manuscript; All the authors approved the final version of the article.
Supported by Joint TCM Science & Technology Projects of National Demonstration Zones for Comprehensive TCM Reform, No. GZY-KJS-ZJ-2025-044; and Ningbo Top Medical and Health Research Program, No. 2023020612.
Institutional animal care and use committee statement: The animal study protocol was approved by the Ethics Committee of the Animal Experiment Center of Ningbo University (No. NBU20230320 April 30, 2023) for studies involving animals.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
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: Yu-Ping Zhou, PhD, Department of Traditional Chinese Medicine, The First Affiliated Hospital of Ningbo University, No. 247 Renmin Road, Jiangbei District, Ningbo 315020, Zhejiang Province, China. fyzhouyuping@nbu.edu.cn
Received: February 2, 2025
Revised: March 31, 2025
Accepted: April 21, 2025
Published online: May 7, 2025
Processing time: 89 Days and 1.6 Hours
Core Tip

Core Tip: This study identifies bicuculline (BIC) as a novel agent for treating metabolic dysfunction-associated steatotic liver disease (MASLD), demonstrating for the first time the dual efficacy of BIC in reducing hepatic lipid accumulation and inflammation via nuclear factor-kappa B (NF-κB) pathway inhibition. Experiments involving zebrafish, mouse, and cellular (HepG2 and AML12) models confirmed that, mechanistically, BIC disrupts the NF-κB signaling pathway, which is a central hub that links metabolic dysfunction and inflammation in MASLD. Transcriptomic insights confirm pathway-specific targeting, distinguishing BIC from broad-spectrum therapies. These findings not only reveal a new axis that can be targeted in the treatment of MASLD but also position BIC as a precision therapeutic candidate with translational promise. The multimodel validation highlights the robustness of BIC, advancing this agent toward clinical exploration.