Kaempferol regulates MAPKs and NF-κB signaling pathways to attenuate LPS-induced acute lung injury in mice

Recent studies show that mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways are two pivotal roles contributing to the development of lipopolysaccharide (LPS)-induced acute lung injury (ALI). The present study aimed to investigate the protective effect of kaempferol (Kae), a naturally occurring flavonoid compound, on ALI and explore its possible mechanisms. Male BALB/c mice with ALI, induced by intranasal instillation of LPS, were treated or not with Kae (100 mg/kg, intragastrically) 1 h prior to LPS exposure. Kae treatment attenuated pulmonary edema of mice with ALI after LPS challenge, as it markedly decreased the lung W/D ratio of lung samples, protein concentration and the amounts of inflammatory cells in BALF. Similarly, LPS mediated overproduction of proinflammatory cytokines in BALF, including TNF-α, IL-1β and IL-6, was strongly reduced by Kae. Histological studies demonstrated that Kae substantially inhibited LPS-induced alveolar wall thickness, alveolar hemorrhage and leukocytes infiltration in lung tissue with evidence of reduced myeloperoxidase (MPO) activity. Kae also efficiently increased superoxide dismutase (SOD) activity of lung sample when compared with LPS group, which was obviously reduced by LPS administration. In addition, Western blot analysis indicated that the activation of MAPKs and NF-κB signaling pathways stimulated by LPS was significantly blocked by Kae. Taken together, our results suggest that Kae exhibits a protective effect on LPS-induced ALI via suppression of MAPKs and NF-κB signaling pathways, which may involve the inhibition of tissue oxidative injury and pulmonary inflammatory process.

► Kaempferol could alleviate tissue oxidative injury in LPS-induced ALI. ► Effect of kaempferol on ALI is attributed to mitigating pulmonary inflammatory response. ► Kaempferol exhibits a protective effect on ALI via suppression of MAPKs and NF-κB signaling pathways. ► Our findings support the potential use of kaempferol for ALI associated with infection by Gram-negative bacteria.