Oridonin Ameliorates Nonalcoholic Steatohepatitis by Regulating Pyroptosis through the NF-κB/NLRP3 Axis

Qianqian Peng, Fengjian He, Shumin Pan, Yinghua Ou^*
Department of Gastroenterology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
* Corresponding Author: Yinghua Ou. Email: email

BIOCELL https://doi.org/10.32604/biocell.2026.081188

Received 25 February 2026; Accepted 26 May 2026; Published online 17 June 2026

Download PDF

Abstract

Background: 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. Methods: An in vitro NASH model was established in HepG2 cells using free fatty acids (FFA), and an in vivo 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. Results: 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 (p < 0.05). Ori also suppressed the expression of fibrosis markers alpha smooth muscle actin (α-SMA), Collagen III, and fibronectin (p < 0.05). In MCD-fed mice, Ori significantly attenuated hepatic steatosis, oxidative stress, inflammation, pyroptosis, and fibrosis, and alleviated liver enzyme levels and stiffness (p < 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. Conclusion: Ori can delay NASH progression via suppressing the NF-κB/NLRP3 pathway, reducing liver cell damage, lipid deposition, inflammation, pyroptosis, and fibrosis.

Graphical Abstract

Oridonin Ameliorates Nonalcoholic Steatohepatitis by Regulating Pyroptosis through the NF-κB/NLRP3 Axis

Keywords

Nonalcoholic steatohepatitis; oridonin; pyroptosis; lipid accumulation; nuclear factor-κB (NF-κB)/nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) pathway