Isostrictiniin Alleviates LPS-Induced Acute Lung Injury via the Regulation of the Keap1-Nrf2/HO-1 and MAPK/NF-κB Signaling Pathways

This study aimed to investigate the preventive effects of isostrictiniin (ITN) from Nymphaea candida against acute lung injury (ALI) through lipopolysaccharide (LPS)-induced ALI mice and LPS-induced A549 cells. Compared with the model group, ITN (50 and 100 mg/kg) significantly reduced the lung indexes, W/D rates, BALF WBC counts, and total protein contents in ALI mice (p < 0.05), as well as the blood neu counts (p < 0.01), while increasing the blood lym counts (p < 0.01). ITN (50 and 100 mg/kg) also markedly decreased the lung tissue TNF-α, IL-6, IL-1β, MDA, and MPO activities in ALI mice (p < 0.01) and enhanced the SOD and GSH levels (p < 0.01). Additionally, ITN (50 and 100 mg/kg) significantly improved lung histopathological damage in ALI mice. Moreover, ITN (10 and 25 µM) significantly reduced the NO, PGE2, IL-1β, IL-6, TNF-α, and MDA levels in LPS-induced A549 cells (p < 0.01) while significantly increasing the SOD and GSH activities (p < 0.01). After LPS-induced A549 cells, the Keap1, p-JNK/JNK, p-ERK1/2/ERK1/2, p-P38/P38, p-IκBα/IκBα, and p-NF-κBp65/NF-κB p65 levels were significantly upregulated (p < 0.05), whereas the Nrf2 and HO-1 protein expressions were downregulated (p < 0.05). After treatment with ITN (25 μM), the changes in these relative protein expressions in LPS-induced A549 cells were significantly reversed (p < 0.05). The above results indicate that ITN has a better preventive effect against ALI, and its mechanisms are related to the regulation of the Keap1-Nrf2/HO-1 and MAPK/NF-κB signaling pathways.

A549; Keap1-Nrf2/HO-1 signaling pathway; MAPK/NF-κB pathway; Nymphaea candida; acute lung injury; anti-inflammatory; isostrictiniin.