Umbelliferone attenuates lipopolysaccharide-induced acute lung injury linked with regulation of TLRs–MyD88 and RIP140/NF-κB signaling pathways

Abstract

Umbelliferone (Umb), isolated from the chloroform fraction of Potentilla evestita, exerts a variety of pharmacological activities. The aim of the present study was to evaluate the protective effects and possible mechanisms of Umb on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Male BALB/c mice were randomly divided into five groups: control group, LPS group, LPS + dexamethasone (Dex, 2 mg kg⁻¹) group, LPS + Umb (20 mg kg⁻¹) group, and LPS + Umb (Umb, 40 mg kg⁻¹) group. Umb and Dex were orally administered 15 min before the intra-tracheal (IT) administration of LPS. 6 h later, the mice were sacrificed. The lung tissues and bronchoalveolar fluid (BALF) were prepared for further analysis. Our results showed that pretreatment with Umb prior to the LPS challenge significantly decreased the lung W/D weight ratio, total leukocyte number and neutrophil percentage in the BALF. Umb also reduced pulmonary MPO activity and alleviated histopathological alteration. Besides, the contents of inflammatory cytokines including interleukin (IL)-6, interleukin (IL)-1β and tumor neurosis factor (TNF)-α were also found to be significantly inhibited by Umb in BALF. Furthermore, the expressions of TLR2, TLR4, MyD88, receptor-interacting protein 140 (RIP140), RelA, CBP, nuclear factor kappa B (NF-κB), caspase-9, caspase-3, Bax in lung tissues were inhibited and Bcl-2 expression was increased in the LPS + Umb group. These results showed that administration of Umb could attenuate LPS-induced ALI, possibly via the anti-inflammatory and anti-apoptotic activities through the TLRs–MyD88 and RIP140/NF-κB pathway.