Zerumbone Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Suppressing the NLRP3/Caspase-1/GSDMD Signalling Pathway.

Abstract

A cyclic sesquiterpene with 11 carbon atoms is the primary component of essential oils from the wild ginger species, Zingiber zerumbet. It exhibits pharmacological effects, including anti-inflammatory and antioxidant properties. However, limited information exists regarding its role in pyroptosis during acute lung injury (ALI). Herein, we investigated how zingerone affects pyroptosis in a murine lipopolysaccharide (LPS)-induced ALI model established via intraperitoneal zerumbone (Zer) administration. Bronchoalveolar lavage fluid, serum, and lung tissue samples were collected after 24 h. Haematoxylin and eosin staining was performed to assess lung tissue damage. Western blot analysis and real-time quantitative polymerase chain reaction (qRT-PCR) were used to quantify protein expression levels associated with pyroptosis. Before LPS exposure, mouse alveolar epithelial (MLE)-12 cells were pretreated with 10 μM Zer for 2 h and then incubated with 1 ng/mL LPS for an additional 24 h. Zer treatment reduced lung tissue injury, inflammation, and oxidative stress in model mice. Zer counteracted pyroptosis in the alveolar epithelial cells of these mice. In MLE-12 cells, Zer significantly inhibited oxidative stress and inflammation. Zer suppressed NLRP3/Caspase-1/GSDMD signalling, pivotal in pyroptosis, mitigating ALI progression. A potential novel therapeutic agent for ALI inhibited the NLRP3/GSDMD signalling pathway involved in pyroptosis.