Gefu Chi1,2, Weiting Zhong3, Yan Liu3, Gejin Lu3, Hongming Lü3, Dacheng Wang4, Fei Sun5. 1. Institute of Frontier Medical Science, Jilin University, Changchun, 130021, People's Republic of China. 2. Department of Outpatient Clinic, The Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, 028000, People's Republic of China. 3. College of Veterinary Medicine, Jilin University, Changchun, 130062, People's Republic of China. 4. College of Veterinary Medicine, Jilin University, Changchun, 130062, People's Republic of China. wdc9928@yahoo.com.cn. 5. Institute of Frontier Medical Science, Jilin University, Changchun, 130021, People's Republic of China. sunfei_1234@126.com.
Abstract
OBJECTIVE AND DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE AND DESIGN: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. RESULTS: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. CONCLUSIONS: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.
Authors: Gordon D Rubenfeld; Ellen Caldwell; Eve Peabody; Jim Weaver; Diane P Martin; Margaret Neff; Eric J Stern; Leonard D Hudson Journal: N Engl J Med Date: 2005-10-20 Impact factor: 91.245
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