Publication Name	World Journal of Gastroenterology
Manuscript ID	105438
Country	China

Category	Gastroenterology & Hepatology
Manuscript Type	Basic Study
Article Title	Bicuculline ameliorates metabolic dysfunction-associated steatotic liver disease by inhibiting the nuclear factor-kappa B pathway and reducing lipid accumulation
Manuscript Source	Unsolicited Manuscript
All Author List	Xiao-Mei Wang, Ze Dai, Dai-Jun Lu, Chao-Qun Bao, Nai-Bin Yang and Yu-Ping Zhou
Funding Agency and Grant Number	Funding Agency Grant Number Joint TCM Science & Technology Projects of National Demonstration Zones for Comprehensive TCM Reform GZY-KJS-ZJ-2025-044 Ningbo Top Medical and Health Research Program 2023020612
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
Key Words	Metabolic dysfunction-associated steatotic liver disease; Bicuculline; Nuclear factor-kappa B; Lipid metabolism; Lipid accumulation; Hepatic steatosis
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.
Citation	<p>Wang XM, Dai Z, Lu DJ, Bao CQ, Yang NB, Zhou YP. Bicuculline ameliorates metabolic dysfunction-associated steatotic liver disease by inhibiting the nuclear factor-kappa B pathway and reducing lipid accumulation. <i>World J Gastroenterol</i> 2025; 31(17): 105438</p>

Received	2025-02-02 05:34
Peer-Review Started	2025-02-02 05:34
To Make the First Decision
Return for Revision	2025-03-18 20:53
Revised	2025-03-31 05:40
Second Decision	2025-04-21 02:36
Accepted by Journal Editor-in-Chief
Accepted by Executive Editor-in-Chief	2025-04-21 06:28
Articles in Press	2025-04-21 06:28
Publication Fee Transferred	2025-04-02 05:37
Edit the Manuscript by Language Editor
Typeset the Manuscript	2025-04-24 08:56

ISSN	1007-9327 (print) and 2219-2840 (online)
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