Chelerythrine Attenuates the Inflammation of Lipopolysaccharide-Induced Acute Lung Inflammation Through NF-κB Signaling Pathway Mediated by Nrf2

Abstract

Chelerythrine (CH), is a kind of benzo[c] phenanthridine alkaloid isolated from plants such as Chelidonium, with pharmacological activities as antitumor, antibiosis and anti-inflammation. However, few studies have demonstrated whether CH could protect against lipopolysaccharide (LPS)-induced acute lung injury (ALI), and the underlying mechanism is also uncertain. The purpose of the present study was to investigate the anti-inflammatory effects of CH on LPS-induced ALI in mice and in RAW264.7 cells. In this study, we demonstrated that treatment with CH significantly ameliorated LPS-induced pathological changes in the lung. CH also attenuated LPS-induced W/D ratio, inflammatory cell infiltration. Meanwhile, LPS-induced Tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β) production and oxidative stress were markedly suppressed by CH. Furthermore, western blot showed that CH suppressed LPS-stimulated inflammation of RAW264.7 cells through activation of nuclear factor kappa-B (NF-κB) pathway. Knocking down of nuclear factor erythroid 2-related factor 2 (Nrf2) led to the reduction of nuclear translocation of the NF-κB p65, which triggered inflammation. These experimental results provided evidence that CH could be a potential therapeutic candidate for the intervention of ALI caused by LPS.

Dihydroartemisinin attenuates lipopolysaccharide‑induced acute lung injury in mice by suppressing NF‑κB signaling in an Nrf2‑dependent manner

“…The Nrf2/ARE signaling pathway also regulates the expression of anti-inflammatory genes and inhibits the progression of inflammation (33). Nrf2 negatively regulates LPS-induced NF-κB signaling activation (29). The present study demonstrated that Nrf2 blockade markedly diminished the inhibition of NF-κB/p65 translocation induced by DHA in macrophages, which indicated that DHA inhibits the NF-κB pathway in a Nrf2-dependent manner in macrophages.…”

Diethyl Blechnic Exhibits Anti-Inflammatory and Antioxidative Activity via the TLR4/MyD88 Signaling Pathway in LPS-Stimulated RAW264.7 Cells

“…Under normal physiological conditions, NRF2 is stored in the cytoplasm combined with the inhibitory protein Keap1 [45]. When stimulated by oxidative stress, NRF2 is dissociated from Keap1, transferred to the nucleus, and combined with antioxidant response elements (ARE), where it activates the transcription of the HO-1 gene to achieve antioxidant effects [46][47][48][49]. Our results showed that DB blocked LPS-induced translocation of Nrf2 from the nucleus into the cytoplasm, which was further confirmed by immunofluorescence analysis and the nuclear and cytoplasmic protein extraction kit.…”

Carotenoid Extract Derived from Euglena gracilis Overcomes Lipopolysaccharide-Induced Neuroinflammation in Microglia: Role of NF-κB and Nrf2 Signaling Pathways

“…Despite the large number of studies on anti-inflammatory effects of carotenoids, the underlying mechanisms remain unclear. Several natural products exert anti-inflammatory effects by influencing NF-κB signaling, able to modulate the expression of genes for inflammatory cytokines [69][70][71][72]. In particular, mechanistic in vitro studies have shown that carotenoids can reduce NF-κB activation by binding to the kinase responsible for the phosphorylation of IκBα, blocking its ubiquitylation and dissociation, and preventing the translocation of p65 subunit to the nucleus, preventing the downstream production of inflammatory cytokines [58,73].…”