Protective effect of cryptotanshinone on lipopolysaccharide-induced acute lung injury in mice.

Crytotanshinone (CTN), one of the main constituents of tanshinones, has been reported to exhibit anti-tumor, anti-inflammatory and other important therapeutic activities. The aim of this study was to investigate the potential therapeutic effects of CTN on murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Male BALB/c mice were pretreated with dexamethasone or CTN 1h before intranasal instillation of LPS. Seven hours after LPS administration, the myeloperoxidase (MPO) in lung tissues, lung wet/dry weight ratio and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The effects of CTN on pro-inflammatory cytokines and signaling pathways were analyzed by enzyme-linked immunosorbent assay (ELISA) and Western blot. The results showed that CTN significantly inhibited LPS induced increases of macrophages and neutrophils infiltration of lung tissues, as well as markedly attenuated MPO activity. Furthermore, CTN significantly reduced the wet/dry weight ratio of lungs and the concentrations of TNF-α, IL-6 and IL-1β in BALF. Compared with LPS group, lung histopathologic changes were less pronounced in the CTN pretreated mice. Additionally, western blotting showed that CTN efficiently inhibited the phosphorylation of IκB-α, p65 NF-κB and the expression of TLR4. Taken together, our results suggest that the anti-inflammatory effects of CTN against LPS-induced acute lung injury may be due to its ability to inhibit TLR4 mediated NF-κB signaling pathways. CTN may be a promising potential therapeutic reagent for ALI treatment.

Tang Y ，Chen Y ，Chu Z ，Yan B ，Xu L ... -  《-》

Protective effect of taraxasterol on acute lung injury induced by lipopolysaccharide in mice.

Taraxasterol, a pentacyclic-triterpene isolated from Taraxacum officinale, has been reported to have potent anti-inflammatory properties. However, the effect of taraxasterol on lipopolysaccharide (LPS)-induced mice acute lung injury has not been investigated. The aims of this study were to investigate whether taraxasterol could ameliorate the inflammation response in LPS-induced acute lung injury and to clarify the possible mechanism. Male BALB/c mice were pretreated with taraxasterol 1h before intranasal instillation of LPS. 7h after LPS administration, the myeloperoxidase (MPO) in lung tissues, lung wet/dry ratio and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were detected. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) in the BALF were measured by ELISA. The extent of phosphorylation of IκB-α, p65 NF-κB, p46-p54 JNK, p42-p44 ERK, and p38 were determined by western blotting. The results showed that taraxasterol attenuated the infiltration of inflammatory cells, the activity of myeloperoxidase (MPO), lung wet/dry ratio, and the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in a dose-dependent manner. Additionally, western blotting results showed that taraxasterol inhibited the phosphorylation of IκB-α, p65 NF-κB, p46-p54 JNK, p42-p44 ERK, and p38 caused by LPS. Our data suggest that anti-inflammatory effects of taraxasterol against the LPS-induced ALI may be due to its ability of inhibition of the NF-κB and MAPK signaling pathways.

San Z ，Fu Y ，Li W ，Zhou E ，Li Y ，Song X ，Wang T ，Tian Y ，Wei Z ，Yao M ，Cao Y ，Zhang N ... -  《-》

Protective effect of veratric acid on lipopolysaccharide-induced acute lung injury in mice.

Veratric acid, a simple benzoic acid derived from plants and fruits, has been reported to exhibit antibacterial, anti-inflammatory and other important therapeutic activities. The aim of this study was to detect the effects of veratric acid on LPS-induced acute lung injury and to investigate the effects of veratric acid on NF-κB signaling pathway. Male BALB/c mice were pretreated with dexamethasone or veratric acid 1h before intranasal instillation of LPS. 7h after LPS administration, the myeloperoxidase in lung tissues, lung wet/dry weight ratio and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The effects of veratric acid on pro-inflammatory cytokines and signal pathways were analyzed by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The results showed that veratric acid inhibited LPS-induced TNF-α, IL-6 and IL-1β production in a dose dependent manner. It was also observed that veratric acid attenuated lung histopathologic changes. The wet/dry weight ratio of lungs and the number of total cells, neutrophils, macrophages in the BALF were all decreased. Furthermore, veratric acid inhibited the phosphorylation of NF-κB p65 and IκB. These results indicate that veratric acid inhibits NF-κB signaling pathways to attenuate inflammatory injury induced by LPS. Veratric acid may be a potential therapeutic reagent for acute lung injury treatment.

Ran X ，Chao S ，Jun-Gang Z ，Yun H ，Kuan-Bing C ，Wen-Jun S ... -  《-》

The effect of magnolol on the Toll-like receptor 4/nuclear factor κB signaling pathway in lipopolysaccharide-induced acute lung injury in mice.

Magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis has been reported to have anti-inflammatory properties. The purpose of this study was to evaluate the effect of magnolol on acute lung injury induced by lipopolysaccharide in mice. Male BALB/c mice were pretreated with dexamethasone or magnolol 1 h before intranasal instillation of lipopolysaccharide (LPS). 7 h after LPS administration, the myeloperoxidase in lung tissues, lung wet/dry weight ratio and inflammatory cells in the bronchoalveolar lavage fluid were determined. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in the bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay (ELISA). The extent of phosphorylation of nuclear factor of inhibitory kappa B alpha (IκB-α), nuclear factor kappa-B (NF-κB) p65 and the expression of Toll-like receptor-4 (TLR4) were detected by western blot. The results showed that magnolol markedly attenuated the histological alterations in the lung; reduced the number of total cells, neutrophils, and macrophages in the bronchoalveolar lavage fluid; decreased the wet/dry weight ratio of lungs in the bronchoalveolar lavage fluid; down-regulated the level of pro-inflammatory mediators, including TNF-α, IL-1β and IL-6; inhibited the phosphorylation of IκB-α, NF-κB p65 and the expression of TLR4, caused by LPS. Taken together, our results suggest that anti-inflammatory effects of magnolol against the LPS-induced acute lung injury may be due to its ability of inhibition TLR4 mediated NF-κB signaling pathways. Magnolol may be a promising potential therapeutic reagent for acute lung injury treatment.

Yunhe F ，Bo L ，Xiaosheng F ，Fengyang L ，Dejie L ，Zhicheng L ，Depeng L ，Yongguo C ，Xichen Z ，Naisheng Z ，Zhengtao Y ... -  《-》

Preventive and therapeutic effects of Danhong injection on lipopolysaccharide induced acute lung injury in mice.

Danhong injection (DHI), a Chinese Materia Medica standardized product extracted from Radix et Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Labiatae, Danshen in Chinese) and Flos Carthami (Carthamus tinctorius L., Compositae, Honghua in Chinese), has been reported to have anti-inflammatory, anti-oxidative and anti-fibrinolytic properties, which is used extensively for the treatment of cardiovascular diseases in clinic. The present study aimed to investigate the preventive and therapeutic effects of DHI on lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice. Lung injury was induced by intranasal instillation with 10 μg LPS. Mice were randomly divided into four groups: Control group; LPS group; LPS+5 ml/kg DHI group and LPS+10 ml/kg DHI group. The effects of DHI on LPS-induced neutrophils influx, inflammatory cytokines release, protein leakage, myeloperoxidase (MPO) and superoxide dismutase (SOD) activities, malondialdehyde (MDA) level were examined. In addition, the NF-κB activation in lung tissues was detected by Western blot. In LPS challenged mice, DHI significantly reduced the infiltration of activated neutrophils and decreased the levels of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF). DHI also inhibited protein extravasation in BALF, attenuated edema and the pathological changes in the lung. In addition, DHI markedly prevented LPS-induced elevation of MDA and MPO levels, as well as reduction of SOD activity. Further study demonstrated that DHI effectively inhibited the NF-κB activation in lung tissues. DHI has been demonstrated to protect mice from LPS induced acute lung injury by its anti-inflammatory and anti-oxidant activities.

Wan LM ，Tan L ，Wang ZR ，Liu SX ，Wang YL ，Liang SY ，Zhong JB ，Lin HS ... -  《-》