@Article{biocell.2026.081188,
AUTHOR = {Qianqian Peng, Fengjian He, Shumin Pan, Yinghua Ou},
TITLE = {Oridonin Ameliorates Nonalcoholic Steatohepatitis by Regulating Pyroptosis through the NF-κB/NLRP3 Axis},
JOURNAL = {BIOCELL},
VOLUME = {},
YEAR = {},
NUMBER = {},
PAGES = {{pages}},
URL = {http://www.techscience.com/biocell/online/detail/27241},
ISSN = {1667-5746},
ABSTRACT = {<b>Background:</b> Nonalcoholic steatohepatitis (NASH) is a liver disease characterized by inflammation and fibrosis. Oridonin (Ori) exhibits anti-inflammatory and anti-fibrotic properties, but its role in NASH remains unclear. The study aimed to investigate whether Ori alleviates NASH injury by regulating pyroptosis through the nuclear factor-κB (NF-κB)/nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) axis. <b>Methods:</b> An <i>in vitro</i> NASH model was established in HepG2 cells using free fatty acids (FFA), and an <i>in vivo</i> model was induced in mice using a methionine-choline-deficient (MCD) diet. Biochemical assays, staining, flow cytometry, Western blot, and immunofluorescence assessed lipid accumulation, oxidative stress, inflammation, pyroptosis, and fibrosis. <b>Results:</b> Ori treatment (2.5–10 μM) dose-dependently reduced FFA-induced cell injury, lipid accumulation, reactive oxygen species (ROS) production, and release of interleukin (IL)-1β and IL-18, while decreasing PI and Caspase-1-positive cells and expression of N-GSDMD (<i>p</i> < 0.05). Ori also suppressed the expression of fibrosis markers alpha smooth muscle actin (α-SMA), Collagen III, and fibronectin (<i>p</i> < 0.05). In MCD-fed mice, Ori significantly attenuated hepatic steatosis, oxidative stress, inflammation, pyroptosis, and fibrosis, and alleviated liver enzyme levels and stiffness (<i>p</i> < 0.05). Mechanistically, Ori inhibited NF-κB activation (p-p65 and p-IκBα) and NLRP3 inflammasome assembly, as confirmed by lipopolysaccharide (LPS)/adenosine triphosphate (ATP) experiments. <b>Conclusion:</b> Ori can delay NASH progression via suppressing the NF-κB/NLRP3 pathway, reducing liver cell damage, lipid deposition, inflammation, pyroptosis, and fibrosis.},
DOI = {10.32604/biocell.2026.081188}
}