lignans and Pulmonary-Edema

Acute lung injury (ALI) has a high morbidity and mortality rate due to the serious inflammation and edema occurred in lung. Magnolol extracted from Magnolia officinalis, has been reported to exhibit anti-inflammatory, and antioxidant activities. Peroxisome proliferator-activated receptors (PPARs) are known to exert a cytoprotective effect against cellular inflammatory stress and oxidative injury. The aim of this study was to explore the involvement of PPAR-γ in the beneficial effect of magnolol in lipopolysaccharide (LPS)-induced ALI. We found that treatment with magnolol greatly improved the pathological features of ALI evidenced by reduction of lung edema, polymorphonuclear neutrophil infiltration, ROS production, the levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF), the expression of iNOS and COX-2, and NF-κB activation in lungs exposed to LPS. Importantly, magnolol is capable of increasing the PPAR-γ expression and activity in lungs of ALI. However, blocking PPAR-γ activity with GW9662 markedly abolished the protective and anti-inflammatory effects of magnolol. Taken together, the present study provides a novel mechanism accounting for the protective effect of magnolol in LPS-induced ALI is at least partly attributed to induction of PPAR-γ in lungs, and in turn suppressing NF-κB-related inflammatory responses.

Topics: Acute Lung Injury; Anilides; Animals; Anti-Inflammatory Agents, Non-Steroidal; Biphenyl Compounds; Bronchoalveolar Lavage Fluid; Cytokines; Lignans; Lipopolysaccharides; Male; Neutrophil Infiltration; NF-kappa B; Oxidative Stress; Peroxidase; PPAR gamma; Pulmonary Edema; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species

In this study, we aimed to investigate our hypothesis starting that Schisantherin A (SchA), which exerts significant anti-inflammatory effects in vitro, could reduce the pulmonary inflammatory response in an acute lung injury (ALI) model. ALI was induced in mice by exposure to lipopolysaccharide (LPS, 20 mg/kg), and the inflammatory mediator production, neutrophil infiltration, and histopathological changes were evaluated. SchA at a dose of 100 mg/kg significantly improved survival rate of mice injected with LPS. The levels of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF) and the histopathological changes due to the injury were significantly inhibited when SchA was administered before or after LPS insult, and the infiltration of neutrophils and macrophages in lung tissues induced by LPS were suppressed by SchA. Additionally, pretreatment with SchA notably blocked the activation of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs). Taken together, SchA showed obvious anti-inflammatory effects in an LPS-induced ALI model via blockage of the NF-κB and MAPK pathways. Thus, SchA may be an innovative therapy for inflammatory diseases.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Cell Movement; Cyclooctanes; Dioxoles; Disease Models, Animal; Dose-Response Relationship, Drug; Lignans; Lipopolysaccharides; Male; Malondialdehyde; Mice; Mice, Inbred BALB C; Neutrophil Infiltration; Neutrophils; Peroxidase; Pulmonary Edema; Signal Transduction; Superoxide Dismutase; Survival Analysis

Hypertonic saline (HTS) administration can decrease the inflammation following ischemia reperfusion. Magnolol is a potent antioxidant. The present study investigated whether combined treatment of magnolol and HTS could provide further protection in mesenteric ischemia reperfusion injury.. Male C3H/HeOuJ mice were randomly segregated into the following groups: sham-operated (sham), vehicle treatment and mesenteric ischemia reperfusion (MSIR) (vehicle-treated), magnolol treatment and MSIR (magnolol-treated), HTS treatment and MSIR (HTS-treated), as well as co-administration of magnolol plus HTS and MSIR (combined-treated). In MSIR, mice were subjected to mesenteric ischemia for 60 min followed by reperfusion for 30 min. Lung injury was evaluated by lung edema (water ratio) and myeloperoxide (MPO) activity; RNA expression of inducible nitric oxide synthetase (iNOS), TNF-α, and IL-6 were assayed by real time RT-PCR. The formation of peroxynitrite in plasma was assayed by the peroxynitrite-dependent oxidation of dihydrorhodamine 123 (DHR 123) to rhodamine.. Compared with those in the sham-treated group, lung edema and MPO activity, expressions of iNOS, TNF-α and IL-6, and plasma peroxynitrite were significantly increased in the vehicle-treated group. Significant attenuations of these parameters were found in the magnolol-treated or HTS-treated animals. Combined treatment of magnolol and HTS further suppressed the lung edema, iNOS, and TNF-α expressions, and plasma peroxynitrite, compared with the results of a single treatment of magnolol or HTS.. Compared with single-agent use, co-administration of magnolol and HTS further decreases iNOS expression and plasma peroxynitrite as well as the degree of lung injury from MISR. These results may provide another treatment measure for post-injury immunomodulation.

Topics: Animals; Antioxidants; Biphenyl Compounds; Interleukin-6; Lignans; Lung; Male; Mesentery; Mice; Mice, Inbred C3H; Models, Animal; Nitric Oxide Synthase Type II; Peroxides; Peroxynitrous Acid; Pulmonary Edema; Regional Blood Flow; Reperfusion Injury; Saline Solution, Hypertonic; Tumor Necrosis Factor-alpha