Sclareol ameliorate lipopolysaccharide-induced acute lung injury through inhibition of MAPK and induction of HO-1 signaling.

Sclareol is a natural fragrance compound that is used widely in the cosmetic and food industries. This study examined the effect of sclareol on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Mice were treated with sclareol 1h before an intratracheal (I.T.) LPS challenge to induce an ALI model. The effects on lung tissue and lung injury were evaluated 6h after LPS induction. Pretreatment with sclareol noticeably improved the LPS-induced histological alterations and edema in lung tissue. Sclareol also inhibited the release of pro-inflammatory mediators. Differences in nitric oxide (NO), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, and IL-10 were found in the bronchoalveolar lavage fluid (BALF) 6h after LPS-induced lung injury. This study also found a reduced number of total cells and reduced protein concentrations in the BALF. There were also changes in the pulmonary wet/dry (W/D) weight ratio, antioxidant enzyme activity, and myeloperoxidase activity in lung tissues. Sclareol effectively blocked the phosphorylation of mitogen-activated protein kinases (MAPKs) and impeded the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). The compound boosted the expression of heme oxygenase-1 (HO-1) and inhibited the breakdown of nuclear factor-kappa B (NF-κB) and inhibitor of kappa B (IκBα). To the best of the authors' knowledge, this study is the first to demonstrate that sclareol effectively inhibits acute lung edema, and the results suggest that sclareol may be a potential agent for the treatment of ALI. The potential therapeutic benefits may include the attenuation of LPS-induced pulmonary inflammation due to sclareol's effects on several pathways, including NF-κB, MAPKs and HO-1, as well as the regulation of antioxidant enzyme activity.

Hsieh YH ，Deng JS ，Pan HP ，Liao JC ，Huang SS ，Huang GJ ... -  《-》

Methanol extract of Antrodia camphorata protects against lipopolysaccharide-induced acute lung injury by suppressing NF-κB and MAPK pathways in mice.

Huang GJ ，Deng JS ，Chen CC ，Huang CJ ，Sung PJ ，Huang SS ，Kuo YH ... -  《-》

Picrasma quassiodes (D. Don) Benn. attenuates lipopolysaccharide (LPS)-induced acute lung injury.

Lee JW ，Park JW ，Shin NR ，Park SY ，Kwon OK ，Park HA ，Lim Y ，Ryu HW ，Yuk HJ ，Kim JH ，Oh SR ，Ahn KS ... -  《-》

23-O-acetylshengmanol-3-O-α-L-arabinoside alleviates lipopolysaccharide-induced acute lung injury through inhibiting IκB/NF-κB and MAPK/AP-1 signaling pathways.

Cimicifuga foetida L. is a well-established traditional Chinese medicine with heat-clearing and detoxifying effects and has good therapeutic effect on oral mucosal ulcer and pharyngitis. The rhizome of this herb is rich in triterpenoid glycosides, including 23-O-acetylshengmanol-3-o-α-L-arabinoside (DA). Whether and how DA attenuates acute lung injury (ALI) are unclear. Accordingly, we focused on its anti-inflammatory effects and underlying molecular mechanisms in lipopolysaccharide (LPS)-stimulated ALI mice and RAW264.7 cells. The model of ALI mice was established by exposed intratracheal instillation of LPS. Lung pathological changes were evaluated by hematoxylin and eosin staining. Pulmonary function was assessed by whole-body plethysmography. Total protein content in bronchoalveolar lavage fluid (BALF) was detected by bicinchoninic acid method. Wet/dry lung ratio was used to evaluate the degree of pulmonary edema in mice. The levels of pro-inflammatory mediators were measured using enzyme-linked immunosorbent assay. The relative expression of pro-inflammatory gene mRNA was examined by RT-qPCR. The expression of inflammatory-related proteins was detected by Western blot. RAW264.7 cells were used to test the anti-inflammatory effects of DA in vitro. Cytotoxicity was assessed using a MTT assay. Nitric oxide production was measured by Griess assay. The production and expression of inflammatory mediators and the protein levels of inflammatory signaling molecules in the NF-κB and MAPK pathways were measured. Furthermore, immunofluorescence staining was used to analyze the expression of p-IκBα, p-ERK, and p-p38 in lung macrophages and the nuclear translocation of NF-κB p65 and AP-1 in cells. DA evidently alleviated histopathological changes and ameliorated pulmonary edema. Moreover, DA could reduce excessive inflammatory reaction in lung tissue as manifested by the reduction of proinflammatory mediators (IL-1β, IL-6, TNF-α, MCP-1, iNOS, and COX-2) in BALF, serum, and lung tissues. Further, DA inhibited the activation of the NLRP3/caspase-1 pathway in the lung. DA reduced the production and expression of the proinflammatory mediators above in RAW264.7 cells. Mechanistically, DA remarkably blocked the nuclear translocation of NF-κB p65, suppressed IκBα phosphorylation, and markedly reduced the nuclear translocation of AP-1 and the phosphorylation of ERK and p38. The findings demonstrated that DA exerts anti-inflammatory effects in LPS-stimulated ALI mice and macrophages by downregulating the NLRP3/caspase-1 signaling pathway in lung tissue and the IκB/NF-κB and MAPKs/AP-1 pathways in macrophages, suggesting that DA may be promising in ALI treatment.

Chen C ，Li L ，Liu X ，Zhang D ，Liu Y ，Li Y ... -  《-》

Total flavonoids of Mosla scabra leaves attenuates lipopolysaccharide-induced acute lung injury via down-regulation of inflammatory signaling in mice.

Mosla scabra (Thunb.) C.Y. Wu, belonging to the Labiatae family, is a tomentose and aromatic plant, which is widely used as an antipyretic and antiviral drug for pulmonary diseases and famous for its efficiency in treating colds, fever, pneumonia and chronic bronchitis. To investigate therapeutic effects and possible mechanism of Mosla scabra flavonoids (MF) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Mice were orally administrated with MF once (30 mg/kg or 90 mg/kg) 1 h before LPS challenge. Lung specimens and the bronchoalveolar lavage fluid (BALF) were isolated for histopathological examinations and biochemical analyses 6 h after LPS challenge. Pretreatment with MF could decrease significantly lung wet-to-dry weight (W/D) ratio, lower myeloperoxidase (MPO) activity and total protein concentrations in the BALF, reduce serum levels of NO, TNF-α, IL-1β and IL-6 in ALI model. Additionally, MF attenuated lung histopathological changes and significantly inhibited the phosphorylation of p38 MAPK and translocation of NF-κB p65. These results showed MF significantly attenuate LPS-induced acute lung injury and production of inflammatory mediators via inhibiting MAPK and NF-κB activation, indicating it as a potential therapeutic agent for ALI.

Chen J ，Wang JB ，Yu CH ，Chen LQ ，Xu P ，Yu WY ... -  《-》