peoniflorin and Pulmonary-Edema

Lipopolysaccharide (LPS) plays an important role in Gram-negative bacteria-induced sepsis and multiple organ dysfunction syndrome, which are still the leading cause of high mortality in intensive care units. Although paeoniflorin (Pae) has reportedly exhibited anti-inflammatory effect and protection against immunological liver injury in mice, it is not known whether Pae improve survival in endotoxemic mice. The purpose of this study was to determine the effect of Pae on the mortality, multiple organ dysfunction and cytokine production in lipopolysaccharide (LPS)-treated mice. We found that pretreatment with Pae decreased mortality, reduced lung and kidney injury, decreased serum creatinine level and improve systolic function of heart in mice challenged with LPS. Further experiments showed that Pae inhibited LPS-stimulated tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) release and promoted LPS-induced interleukin-10 (IL-10) production. Our results indicate that Pae protects mice against lethal LPS challenge, at least in part, through inhibiting TNF-α and IL-1β production and accelerating IL-10 expression.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzoates; Bridged-Ring Compounds; Cytokines; Echocardiography; Glucosides; Heart; Interleukin-10; Interleukin-1beta; Kidney; Kidney Function Tests; Lipopolysaccharides; Liver; Liver Function Tests; Lung; Male; Mice; Mice, Inbred BALB C; Monoterpenes; Myocardium; Pulmonary Edema; Survival Analysis; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left

The present study aims to explore the effects of paeoniflorin (PF), a monoterpene glycoside isolated from the roots of Paeonia lactiflora Pallas, on acute lung injury (ALI) and the possible mechanisms.. ALI was induced in mice by an intratracheal instillation of lipopolysaccharide (LPS, 1 mg/kg), and PF was injected intraperitoneally 30 min prior to LPS administration. After 24 h, lung water content, histology, microvascular permeability and proinflammatory cytokines in the bronchoaveolar lavage fluid were evaluated.. It was shown that PF (50, 100 mg/kg) could alleviate LPS-induced ALI, evidenced by reduced pulmonary edema, improved histological changes, and attenuated inflammatory cell accumulation in the interstitium and alveolar space as well as microvascular permeability. It also markedly down-regulated the expressions of proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α at both transcription and protein levels. Additionally, PF inhibited the phosphorylations of p38 MAP kinase (p38) and c-Jun NH2-terminal kinase (JNK) but not extracellular signal-regulated kinase (ERK), and prevented the activation of nuclear factor-kappa B (NF-κB) in the lung tissues.. The findings suggest that PF is able to alleviate ALI, and the underlying mechanisms are probably attributed to decreasing the production of proinflammatory cytokines through down-regulation of the activation of p38, JNK and NF-κB pathways in lung tissues.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzoates; Bridged-Ring Compounds; Extracellular Signal-Regulated MAP Kinases; Glucosides; Inflammation; JNK Mitogen-Activated Protein Kinases; Lipopolysaccharides; Lung Injury; Male; Mice; Mice, Inbred ICR; Microcirculation; Monoterpenes; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Permeability; Phosphorylation; Pulmonary Edema; Signal Transduction; Time Factors