Irigenin attenuates lipopolysaccharide-induced acute lung injury by inactivating the mitogen-activated protein kinase (MAPK) signaling pathway

Abstract

Acute lung injury (ALI) is a serious pulmonary inflammation disease with high mortality. Irigenin, an isoflavone from rhizomes of the Belamcanda chinensis, has been reported to exert anti-inflammatory, anti-oxidative, and anti-apoptotic activities in several diseases. However, it is still unclear whether irigenin can exert a beneficial effect in ALI. A network pharmacology method was utilized to predict the hub targets and potential therapeutic mechanisms of irigenin against ALI. Lipopolysaccharide (LPS) was used to establish the mice model of ALI for evaluating the effects of irigenin. According to the protein-protein interaction (PPI) network, we identified EGFR, HRAS, AKT1, SRC, and HSP90AA1 as the top five significant genes. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment assays showed that irigenin might affect inflammatory response, cytokine production, and cell death by the mitogen-activated protein kinase (MAPK ) signaling pathway. In vivo experiment results manifested that irigenin decreased pathological changes, lung Wet/Dry weight ratio, and total protein content in bronchoalveolar lavage fluid (BALF). Irigenin also reduced the production of inflammatory cytokines, including tumor necrosis factor-a (TNF-a), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-18 (IL-18), and neutrophil infiltration. Additionally, irigenin inhibited pulmonary apoptosis in LPS-treated ALI mice. Moreover, LPS-induced phosphorylation of p38, JNK, and ERK was significantly abated due to the treatment of irigenin. In summary, irigenin ameliorates LPS-induced ALI by suppressing pulmonary inflammation and apoptosis via inactivation of the MAPK signaling pathway. These findings indicated the therapeutic potential of irigenin in ALI.

Integrated network pharmacology, molecular docking, and lipidomics to reveal the regulatory effect of Qingxuan Zhike granules on lipid metabolism in lipopolysaccharide‐induced acute lung injury

“…The protein target MAPK1 (ERK2), known for its regulation of inflammatory responses, cellular apoptosis, and lipid metabolism, was reported to participate in the occurrence and progression of ALI (Liu et al, 2023; Zhang et al, 2023). Naringenin was shown to alleviate inflammation, apoptosis, and ferroptosis associated with lung injury (Zhang et al, 2022).…”

Treadmill training improves lung function and inhibits alveolar cell apoptosis in spinal cord injured rats

“…It has been demonstrated that the MAPK/Erk signaling pathway is implicated in the progression of diverse lung ailments. For instance, irigenin was observed to mitigate LPS-induced lung injury through the inhibition of lung cell apoptosis by restraining the MAPK/Erk signaling pathway 47 . In our study, treadmill training exhibited the ability to suppress the expression of MAP3K3 and p-Erk, resulting in reduced expression of pro-apoptotic factors such as Bax, CytC, caspase 3, and caspase 9, coupled with upregulated expression of the anti-apoptotic factor Bcl-2 within lung tissues of SCI rats.…”

Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)

“…Inactivation of MAPK signaling is also demonstrated to contribute to the anti-inflammatory effects in ARDS treatment. Nicotinamide [ 101 ], Irigenin [ 259 ] and β-Caryophyllene [ 260 ] have been recently found to inhibit MAPK signaling and reduce expression of inflammatory factors in ALI model. Particularly, Dilmapimod, a specific p38MAPK inhibitor, has been reported to have a satisfactory safety profile in trauma patients at risk of developing ARDS and to reduce the concentration of pro-inflammatory cytokines [ 261 ].…”