Recent experimental studies have highlighted the beneficial effects of curcumin on liver injury induced by acetaminophen (APAP). However, the specific molecular mechanisms underlying curcumin’s hepatoprotective effects against APAP-induced liver injury remain to be fully elucidated. This study aimed to investigate the therapeutic effect of curcumin on APAP-induced liver injury using a mouse model. In the experiment, mice were subjected to an intraperitoneal hepatotoxic dose of APAP (300 mg/kg) to induce hepatotoxicity. After 30 min of APAP administration, the mice were treated with different concentrations of curcumin (0, 10, 25, or 50 mg/kg). After 16 h, mice with hepatotoxicity showed elevated levels of serum alanine transaminase (ALT), aspartate transaminase (AST), hepatic myeloperoxidase (MPO), TNF-α, and IL-6, and decreased levels of glutathione (GSH). Moreover, there was an increased infiltration of neutrophils and macrophages following intraperitoneal injection of APAP. However, curcumin-treated mice displayed a pronounced reduction in serum ALT, AST, hepatic MPO, TNF-α, and IL-6 levels, coupled with a notable elevation in GSH levels compared to the APAP-treated hepatotoxic mice. Moreover, curcumin treatment led to reduced infiltration of neutrophils and macrophages. Additionally, curcumin inhibited the phosphorylation of ERK and NF-kB proteins while reducing the expression of cyclooxygenase-2 (COX-2). These findings highlight the hepatoprotective potential of curcumin against APAP-induced liver injury through the suppression of the ERK, NF-kB, and COX-2 signaling pathways.

Acetaminophen (APAP) overdose causes acute liver injury via oxidative stress, uncontrolled inflammatory response, and subsequent hepatocyte death. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is a potent source of cellular reactive oxygen species (ROS) and may contribute to oxidative stress in many inflammatory processes. Corilagin, a component of Phyllanthus urinaria, possesses antioxidant, anti-inflammatory, and hepatoprotective effects. We evaluated the mechanisms underlying the protective effect of corilagin against acetaminophen-induced liver injury. Mice were intraperitoneally administrated 300 mg/kg APAP or equal volume of saline (control), with or without various concentrations of corilagin (0, 1, 5, or 10 mg/kg) administered after 30 min. All animals were sacrificed 16 h after APAP administration, and serum and liver tissue assays including histology, immunohistochemistry, and Western blot assay were performed. Corilagin post-treatment significantly attenuated APAP-induced liver injury (p < 0.005), inflammatory cell infiltration, hepatic proinflammatory cytokine levels, and hepatic oxidative stress. Furthermore, corilagin attenuated the protein levels of NOX1, NOX2, signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) in APAP-induced liver injury. These results indicated that the antioxidant, anti-inflammatory, and protective effects of corilagin in APAP-induced liver injury might involve the regulation of interleukin (IL)-6/STAT3 and mitogen-activated protein kinase (MAPK)/NF-κB signaling pathways through NOX-derived ROS.

Xanthoxylin, a bioactive phenolic compound extracted from the traditional herbal medicine Penthorum Chinense Pursh, is renowned for its anti-inflammatory effects. While previous studies have highlighted the anti-inflammatory and antioxidant properties of Xanthoxylin, its precise mechanisms, particularly concerning immune response and organ protection, remain underexplored. This study aimed to elucidate the effects of Xanthoxylin on inflammation and associated signaling pathways in a mouse model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced via intratracheal administration of LPS, followed by intraperitoneal injections of Xanthoxylin at doses of 1, 2.5, 5, and 10 mg/kg, administered 30 min post-LPS exposure. Lung tissues were harvested for analysis 6 h after LPS challenge. Xanthoxylin treatment significantly mitigated lung tissue damage, pathological alterations, immune cell infiltration, and the production of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Additionally, Xanthoxylin modulated the expression of key proteins in the protein kinase B (Akt)/hypoxia-inducible factor 1-alpha (HIF-1α)/nuclear factor-kappa B (NF-κB) signaling pathway, as well as nuclear factor erythroid 2-related factor 2 (Nrf2) and oxidative markers such as superoxide dismutase (SOD) and malondialdehyde (MDA) in the context of LPS-induced injury. This study demonstrates that Xanthoxylin exerts protective and anti-inflammatory effects by down-regulating and inhibiting the Akt/HIF-1α/NF-κB pathways, suggesting its potential as a therapeutic target for the prevention and treatment of ALI or acute respiratory distress syndrome (ARDS).

Acute lung injury (ALI) and acute respiratory distress syndrome are clinically life-threatening diseases. Corilagin, a major polyphenolic compound obtained from the herb Phyllanthus urinaria, has anti-inflammatory and antioxidant properties, and in this study, we sought to evaluate the protective effects and mechanisms of corilagin on lipopolysaccharide (LPS)-induced ALI in mice. ALI was induced in the mice by the intratracheal administration of LPS, and following 30 min of LPS challenge, corilagin (5 and 10 mg/kg body weight) was administered intraperitoneally. At 6 h post-LPS administration, lung tissues were collected for analysis. Corilagin treatment significantly attenuated inflammatory cell infiltration, the production of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, and oxidative stress in lung tissues. In addition, corilagin inhibited the LPS-induced expression of NOX2, ERK, and NF-κB. Corilagin has anti-oxidative and anti-inflammatory effects, and can effectively reduce ALI via attenuation of the NOX2 and ERK/NF-κB signaling pathways.

Acute lung injury (ALI) and its severe manifestation, acute respiratory distress syndrome (ARDS), are characterized by uncontrolled inflammatory responses, neutrophil activation and infiltration, damage to the alveolar capillary membrane, and diffuse alveolar injury. Neutrophil extracellular traps (NETs), formed by activated neutrophils, contribute significantly to various inflammatory disorders and can lead to tissue damage and organ dysfunction. Corilagin, a compound found in Phyllanthus urinaria, possesses antioxidative and anti-inflammatory properties. In this study, we investigated the protective effects and underlying mechanisms of corilagin in hydrochloric acid (HCl)/lipopolysaccharide (LPS)-induced lung injury. Mice received intraperitoneal administration of corilagin (2.5, 5, or 10 mg/kg) or an equal volume of saline 30 min after intratracheal HCl/LPS administration. After 20 h, lung tissues were collected for analysis. Corilagin treatment significantly mitigated lung injury, as evidenced by reduced inflammatory cell infiltration, decreased production of proinflammatory cytokines, and alleviated oxidative stress. Furthermore, corilagin treatment suppressed neutrophil elastase expression, reduced NET formation, and inhibited the expression of ERK, p38, AKT, STAT3, and NOX2. Our findings suggest that corilagin inhibits NET formation and protects against HCl/LPS-induced ALI in mice by modulating the STAT3 and NOX2 signaling pathways.