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Updated: Sep 10, 2026
Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
Demethoxycurcumin Alleviates Lipopolysaccharide-Induced Acute Lung Injury via Nrf2-Mediated Anti-Inflammation and
Jing Tang1, Qiuni Zhao1, Jue Liu1
1Department of Anesthesiology, NHC Key Laboratory of Birth Defect for Research and Prevention (Hunan Provincial Maternal and Child Health Care Hospital), Changsha, Hunan, 410008, China, hunanfy.com.
Background:
Sepsis-induced acute lung injury (SI-ALI) represents a life-threatening condition driven by dysregulated immune responses and redox imbalance. Demethoxycurcumin (DMC), a bioactive analog of curcumin, exhibits marked anti-inflammatory and free radical-scavenging capacities. Despite its potential, the precise molecular pathways through which DMC mitigates SI-ALI pathogenesis have yet to be fully elucidated.
Methods:
SI-ALI was induced in mice through lipopolysaccharide (LPS) administration. Lung injury was assessed by histopathological analysis and measurement of wet-to-dry (W/D) weight ratios. Oxidative stress markers were quantified using ELISA, and inflammatory cytokine mRNA levels were analyzed by RT-PCR. Ferroptosis-related proteins and Nrf2 pathway activation were evaluated through Western blotting and immunofluorescence. Mitochondrial ultrastructure was examined via transmission electron microscopy (TEM). The involvement of the Nrf2 pathway was further confirmed by using the Nrf2 inhibitor ML385.
Results:
DMC treatment significantly alleviated lung injury in a dose-dependent manner, improving histopathology and reducing W/D weight ratios. It attenuated inflammation by suppressing IL-6, TNF-α, and IL-1β expression and restored oxidative balance by enhancing glutathione (GSH) levels while decreasing malondialdehyde (MDA). Moreover, DMC upregulated glutathione peroxidase 4 (GPX4) and SLC7A11, downregulated cyclooxygenase-2 (COX2) and ACSL4, reduced nonheme iron and 4-hydroxynonenal (4-HNE) production, and improved mitochondrial morphology, collectively demonstrating its inhibitory effects on ferroptosis. Nrf2 inhibition partially reversed these protective effects, underscoring the central role of the Nrf2 pathway in DMC's mechanism of action.
Conclusion:
DMC ameliorates SI-ALI by mitigating inflammation and ferroptosis through Nrf2 pathway activation, suggesting a potential therapeutic strategy for SI-ALI treatment.
