phytoestrogens and Acute-Lung-Injury

The antioxidant and anti-inflammatory features of Formononetin, an isoflavone constituent extracted from traditional Chinese medicine, have been reported. The present study investigated that whether Formononetin plays a benefit on hyperoxic ALI.. C57BL/6 mice were exposed to hyperoxia for 72 h to produce experimental hyperoxic ALI model. Formononetin or vehicle was administrated intraperitoneally. Samples from the lung were collected at 72 h post hyperoxia exposure for further study. Pulmonary microvascular endothelial cells isolated from the lung of C57BL/6 mice were used for in vitro study.. Formononetin pretreatment notably attenuated hyperoxia-induced elevating pulmonary water content, upregulation of proinflammatory cytokine levels and increasing infiltration of neutrophil in the lung. Western blot analyses showed that Formononetin enhanced the expression of nuclear factor erythroid-2-related factor 2 (Nrf2) which is a key transcription factor regulating the expression of heme oxygenase-1 (HO-1). Formononetin increased HO-1 expression and activity compared with vehicle-treated animals. Moreover, Formononetin reversed hyperoxia-caused the reduction of M2 macrophage polarization. However, pretreatment of a HO-1 inhibitor reduced the protective effect of Formononetin on hyperoxic ALI. Cell study showed that the Formononetin-induced upregulation of HO-1 was abolished when the Nrf2 was silenced.. Formononetin pretreatment reduces hyperoxia-induced ALI via Nrf2/HO-1-mediated antioxidant and anti-inflammatory effects.

Topics: Acute Lung Injury; Animals; Disease Models, Animal; Endothelial Cells; Heme Oxygenase-1; Hyperoxia; Isoflavones; Lung; Membrane Proteins; Mice; NF-E2-Related Factor 2; Phytoestrogens

Under septic conditions, Lipopolysaccharide (LPS)-induced apoptosis of lung vascular endothelial cells (ECs) triggers and aggravates acute lung injury (ALI), which so far has no effective therapeutic options. Genistein-3'-sodium sulphonate (GSS) is a derivative of native soy isoflavone, which has neuro-protective effects through its anti-apoptotic property. However, whether GSS protects against sepsis-induced lung vascular endothelial cell apoptosis and ALI has not been determined. In this study, we found that LPS-induced Myd88/NF-κB/BCL-2 signalling pathway activation and subsequent EC apoptosis were effectively down-regulated by GSS in vitro. Furthermore, GSS not only reversed the sepsis-induced BCL-2 changes in expression in mouse lungs but also blocked sepsis-associated lung vascular barrier disruption and ALI in vivo. Taken together, our results demonstrated that GSS might be a promising candidate for sepsis-induced ALI via its regulating effects on Myd88/NF-κB/BCL-2 signalling in lung ECs.

Topics: Acute Lung Injury; Animals; Apoptosis; Endothelium, Vascular; Genistein; Lipopolysaccharides; Lung; Male; Mice; Mice, Inbred C57BL; Phytoestrogens; Protective Agents; Proto-Oncogene Proteins c-bcl-2

The aim of the present study was to assess the effect of seven days daidzein pretreatment in cecal ligation and puncture (CLP) model of sepsis.. We assessed the survival benefit of daidzein and its effect on lung injury in CLP-induced sepsis in mice and determined the bacterial load in peritoneal fluid, blood, and lung homogenates. Tumor necrosis factor α (TNF-α) and corticosterone levels were measured by enzyme-linked immunosorbent assay; relative mRNA expression was estimated by real-time polymerase chain reaction, and standard biochemical techniques were used to measure nitrite level, myeloperoxidase activity, and vascular permeability.. Daidzein pretreatment for seven days at a dose of 1 mg/kg body weight subcutaneously increased the survival time of septic mice. Daidzein decreased the bacterial load in peritoneal fluid, blood, and lungs, reduced the tumor necrosis factor α and nitrite level in plasma, and partially suppressed lung injury by reducing vascular permeability and myeloperoxidase activity in septic mice. Further, it restored the relative mRNA expressions of inducible nitric oxide synthase, glucocorticoid receptor α, and glucocorticoid receptor β genes in septic lungs were restored by daidzein pretreatment.. Daidzein pretreatment for 7 d in sepsis increased the survival time in mice, which may be relate to decrease in bacterial load, anti-inflammatory effect, and protection from lung injury.

Topics: Acute Lung Injury; Animals; Bacterial Load; Biomarkers; Cecum; Corticosterone; Drug Administration Schedule; Enzyme-Linked Immunosorbent Assay; Injections, Subcutaneous; Isoflavones; Male; Mice; Nitric Oxide; Nitrites; Peroxidase; Phytoestrogens; Real-Time Polymerase Chain Reaction; Sepsis; Treatment Outcome; Tumor Necrosis Factor-alpha

Formononetin has shown a variety of pharmacologic properties including anti-inflammatory effect. In the present study, we analyzed the role of formononetin in acute lung injury induced by lipopolysaccharide (LPS) in mice. The cell counting in the bronchoalveolar lavage fluid (BALF) was measured. The animal lung edema degree was evaluated by wet/dry weight ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity was assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators, tumor necrosis factor-α (TNF-α) and IL-6,were assayed by enzyme-linked immunosorbent assay method. Pathological changes of hung tissues were observed by HE staining. Peroxisome proliferator-activated receptor (PPAR)-γ gene expression was measured by real-time PCR. The data showed that treatment with the formononetin group markedly attenuated inflammatory cell numbers in the BALF, increased PPAR-γ gene expression and improved SOD activity and inhibited MPO activity. The histological changes of the lungs were also significantly improved by formononetin compared to LPS group. The results indicated that formononetin has a protective effect on LPS-induced acute lung injury in mice.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Edema; Inflammation; Interleukin-6; Isoflavones; Lipopolysaccharides; Lung; Male; Mice; Mice, Inbred BALB C; Peroxidase; Phytoestrogens; PPAR gamma; Pulmonary Edema; Superoxide Dismutase; Tumor Necrosis Factor-alpha