Abstract:

AIM: To investigate the effects of limonin (LM) on lipopolysaccharides (LPS)-induced acute lung injury (ALI) in mice. METHODS: Forty ICR male mice were divided randomly by weight into 4 groups: normal group, model group, dexamethasone (Dex)-treated group and LM-treated group. Each group had ten mice. Dex and LM were intraperitoneally injected at the dose of 10 mg/kg, respectively. Two hours after drug administration, except the mice in normal group treated with same vehicle, others were intracheally injected with LPS (5 mg/kg). Six hours after LPS challenge, mice were sacrificed and lung tissues were obtained for calculating the pulmonary index and wet/dry mass (W/D) ratio. The sections were stained with hematoxylin and eosin (HE) for histological analysis. The levels of TNF-alfa, IL-1beta, and IL-6 in serum were determined by ELISA. Myeloperoxidase (MPO) in serum were determined by chromatometry. The mRNA expressions of TNF-alfa, IL-1beta and IL-6 were determined by RT-PCR while TLR4 and NF-kB p65 protein by Western blot analysis. RESULTS: Compared with normal group, mice in model group had obvious increase of lung indexes and W/D ratios, which were accompanied by marked inflammatory cell infiltration, alveolar congestion and edema in lung; the levels of TNF-alfa, IL-1beta, IL-6 and MPO in serum as well as their mRNA expressions in the lung of ALI mice were also increased (P<0.01). Compared with model group, lung indexes and W/D ratios were decreased in LM-treated group while histological changes were improved; the levels of TNF-alfa, IL-1beta, and IL-6 in serum (P<0.01) and their mRNA expressions, and the expressions of TLR4 and NF-kB p65 protein in lung tissues were also significantly decreased (P<0.01). CONCLUSION: LM protects against LPS-induced ALI via regulating TLR4/NF-kB pathway and inhibiting expression of inflammatory cytokines in mice.

Key words: limonin, anti-inflammatory effect, lipopolysaccharides, acute lung injury