Inula japonica ameliorated the inflammation and oxidative stress in LPS-induced acute lung injury through the MAPK/NF-κB and Keap1/Nrf2 signalling pathways

Abstract

Objectives To investigate the protective effect and underlying mechanism of Inula japonica (TEIJ) in the treatment of acute lung injury (ALI). Methods Protective effects of TEIJ in the inflammation and oxidative stress were studied in lipopolysaccharide (LPS)-induced ALI mice. Meanwhile, Western blot and real-time qPCR were carried out to investigate the underlying mechanism of TEIJ for ALI as well as immunohistochemistry. Key findings TEIJ significantly alleviated the course of ALI via suppressing the interstitial infiltrated inflammatory cells, the increase of inflammatory factors and the decrease of anti-oxidative factors. TEIJ inactivated the MAPK/NF-κB signalling pathway to suppress the transcription of its downstream target genes, such as TNF-α, IL-6, etc. Meanwhile, TEIJ activated the Keap1/Nrf2 signalling pathway to regulate expression levels of Nrf2 and its target proteins. The results of LC-QTOF-MS/MS indicated potential active constituents of I. japonica, terpenoids and flavonoids. Additionally, terpenoids and flavonoids synergistically alleviated LPS-induced ALI depending on MAPK/NF-κB and Keap1/Nrf2 signalling pathways. Conclusion I. japonica could be considered a potential agent to treat ALI via regulating the MAPK/NF-κB and Keap1/Nrf2 signalling pathways.

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).…”

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

“…However, during ARDS, the anti-oxidative effects by Nrf2 pathway are rapidly overwhelmed by excessive ROS production, or are dysregulated in damaged tissues, leading to aggravate oxidative injury [ 221 , 222 ]. The importance of Nrf2 pathway in mediating antioxidant effects has been well characterized both in vivo and in vitro models of ALI/ARDS [ 102 , 223 ]. In addition to considering general Nrf2 activation, researchers have explored alternative signaling pathways as potential targets for therapy.…”

“…Considering that NF-κB integrates numerous upstream signals, many targets indirectly inhibit NF-κB-mediated inflammation via modulating its upstream signaling. It has been shown that Chrysosplenol D [ 239 ], Daphnetin [ 165 ] and Inula japonica [ 102 ] ameliorate acute lung inflammation by suppressing the MAPK-mediated NF-κB pathway. The molecular BAP31 as well as Schisandrin B have presented therapeutic value by targeting MyD88 to reduce NF-κB activation in ALI mice [ 240 , 241 ].…”

“…Recent studies have underscored the pivotal role of the MAPK pathway in the inflammatory processes in ARDS, primarily through the facilitation of the release of inflammatory cytokines and chemokines [97][98][99]. Besides, accumulating evidence have demonstrated that MAPK activation aggravates lung inflammation of ARDS by upregulating the activity of NLRP3 inflammasome and NF-κB in animal models [100][101][102]. In addition, previous studies have revealed the involvement of the MAPK pathway in eliciting tissue factor expression in endothelial cells under inflammatory stimuli such as TNF-α and C-reactive protein, which results in activating the coagulation system and fibrin deposition (Fig.…”

Characterization of Sesquiterpene Dimers from the Flowers of Inula japonica and the Structural Revisions of Related Compounds

“…Notably, sesquiterpene dimers (SDs) possess more attractive constituents and remarkable pharmacological activities compared with sesquiterpene monomers. Such SDs exhibit diverse and significant bioactivities, including anti-inflammatory, antifungal, antibacterial, antidiabetic, and hypolipidemic. , The complex polycyclic systems and multichiral centers often lead to structural misassignment of SDs, especially when the assignment is only based on spectroscopic data . The configurations of SDs are mainly determined by the NOE correlations in most investigations.…”