Arctigenin Prevents Metabolic Dysfunction-associated Steatohepatitis by Inhibiting NLRP3/GSDMD-N Axis in Macrophages
Year: 2025
Type: article
Abstract: Background and Aims: , exhibits anti-inflammatory activity. Therefore, we aimed to examine its potential protective role against MASH and explore the underlying mechanisms. Methods: to verify the ATG targets. Results: ATG administration prevented the progression of MASH in a dose-dependent manner. High-dose ATG significantly reduced hepatic macrophage and neutrophil infiltration, serum enzyme levels, and lipid peroxidation, while enhancing antioxidant enzyme activity. Mechanistic network pharmacology identified modulation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome as the central pathway underlying ATG's bioactivity. Functional analyses in lipopolysaccharide-stimulated RAW264.7 cells confirmed that ATG inhibited NLRP3 expression, pyroptosis-related protein cleavage (hereinafter referred to as GSDMD-N), and pro-inflammatory chemokine production in a concentration-dependent manner. Notably, ATG disrupted NLRP3/GSDMD-N axis activity in macrophages without causing cellular toxicity. Conclusions: ATG may inhibit the inflammatory cascade primarily by targeting macrophage NLRP3 inflammasomes, thereby preventing the progression of MASH.
Authors: Rui Xue, Lu Jiang, Qian-Ren Zhang, Qing-Jing Wang, Rui-Xu Yang, Tian-Yi Ren, Qin Pan, Jian-Gao Fan
Institutions: Shanghai Jiao Tong University, XinHua Hospital
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4413484901