3-methylquercetin and Pulmonary-Edema

Isorhamnetin has been reported to have anti-inflammatory, anti-oxidative, and anti-proliferative effects. The aim of this study was to investigate the protective effect of isorhamnetin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice by inhibiting the expression of cyclooxygenase-2 (COX-2). The effects of isorhamnetin on LPS-induced lung pathological damage, wet/dry ratios and the total protein level in bronchoalveolar lavage fluid (BALF), inflammatory cytokine release, myeloperoxidase (MPO) and superoxide dismutase (SOD) activities, and malondialdehyde (MDA) level were examined. In addition, the COX-2 activation in lung tissues was detected by Western blot. Isorhamnetin pretreatment improved the mice survival rates. Moreover, isorhamnetin pretreatment significantly attenuated edema and the pathological changes in the lung and inhibited protein extravasation in BALF. Isorhamnetin also significantly decreased the levels of inflammatory cytokines in BALF. In addition, isorhamnetin markedly prevented LPS-induced oxidative stress. Furthermore, isorhamnetin pretreatment significantly suppressed LPS-induced activation of COX-2. Isorhamnetin has been demonstrated to protect mice from LPS-induced ALI by inhibiting the expression of COX-2.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Antioxidants; Bronchoalveolar Lavage Fluid; Cyclooxygenase 2; Cytokines; Enzyme Activation; Interleukin-1beta; Lipopolysaccharides; Lung; Male; Malondialdehyde; Mice; Mice, Inbred BALB C; Oxidative Stress; Peroxidase; Pulmonary Edema; Quercetin; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Isorhamnetin (Isor), a 3-O-methylated metabolite of quercetin, has shown antioxidant and anti-proliferative effects in previous studies. In this study, we investigated the anti-inflammatory effect of Isor on LPS-induced acute lung injury (ALI). Accordingly, we evaluated the effect of Isor on cytokine production elevated by LPS (1 μg/ml) in vitro. An in vivo ALI murine model was also established via lipopolysaccharide inhalation (LPS, 20 mg/kg), and the cytokine levels and inflammatory cell count in bronchoalveolar lavage fluid (BALF) were evaluated. The observed lung injury was assessed using histopathologic sections via H&E straining. Furthermore, to investigate whether the anti-inflammatory effect of Isor is associated with NF-κB and MAPKs pathway activation, the phosphorylated levels of ERK, JNK, IκBa and NF-κB(p65) were determined.. Isor significantly inhibited LPS-induced TNF-α, IL-1β and IL-6 secretion both in vitro and in vivo. Neutrophil infiltration and edema in an ALI model were substantially alleviated. The histopathological changes induced by LPS were lessened by Isor. Additionally, Isor notably suppressed the phosphorylation of ERK, JNK, IκBa and NF-κB(p65) activated by LPS in vivo.. Isor showed efficient protective effects on an LPS-induced ALI model. MAPKs and NF-κB pathways are critical for Isor to perform its protective effects.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Cytokines; Lipopolysaccharides; Lung; Male; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases; Neutrophil Infiltration; NF-kappa B; Pulmonary Edema; Quercetin; RAW 264.7 Cells