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Apigenin-7-glycoside prevents LPS-induced acute lung injury via downregulation of oxidative enzyme expression and protein activation through inhibition of MAPK phosphorylation.

Li KC, Ho YL, Hsieh WT, Huang SS, Chang YS, Huang GJ - Int J Mol Sci (2015)

Bottom Line: Additionally, inflammation, which can decrease the activities of antioxidative enzymes (AOEs) is also observed in these studies.At the same time, flavonoids are reported to promote the activities of heme oxygenase-1 (HO-1) decreased by LPS.Meanwhile, our data revealed that AP7Glu not only did significantly inhibit the LPS-enhanced inflammatory activity in lung, but also exhibited anti-inflammatory effect through the MAPK and inhibitor NF-κB (IκB) pathways.

View Article: PubMed Central - PubMed

Affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 404, Taiwan. u9852852@cmu.edu.tw.

ABSTRACT
Apigenin-7-glycoside (AP7Glu) with multiple biological activities is a flavonoid that is currently prescribed to treat inflammatory diseases such as upper respiratory infections. Recently, several studies have shown that its anti-inflammatory activities have been strongly linked to the inhibition of secretion of pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOs) and cyclooxygenase-2 (COX-2) induced through phosphorylation nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPK) pathways. Additionally, inflammation, which can decrease the activities of antioxidative enzymes (AOEs) is also observed in these studies. At the same time, flavonoids are reported to promote the activities of heme oxygenase-1 (HO-1) decreased by LPS. The purpose of this study was to assess these theories in a series of experiments on the suppressive effects of AP7Glu based on LPS-induced nitric oxide production in RAW264.7 macrophages in vitro and acute lung injury in mice in vivo. After six hours of lipopolysaccharide (LPS) stimulation, pulmonary pathological, myeloperoxidase (MPO) activity, total polymorphonuclear leukocytes (PMN) cells, cytokines in bronchoalveolar lavage fluid (BALF) and AOEs, are all affected and changed. Meanwhile, our data revealed that AP7Glu not only did significantly inhibit the LPS-enhanced inflammatory activity in lung, but also exhibited anti-inflammatory effect through the MAPK and inhibitor NF-κB (IκB) pathways.

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Related in: MedlinePlus

AP7Glu improved pulmonary edema in vivo. Seventy-two hours after LPS injection with or without AP7Glu pretreatments, mice were exsanguinated and their right lower lungs were obtained. (A) The right lower lungs were used to assess wet to dry (W/D) ratio of lung; (B) Severity of lung injury was analyzed by the lung injury scoring system. Each value represents as mean ± SD of 6 mice. ### compared with sample of control group. **p < 0.01, and ***p < 0.001 were compared with LPS-alone group.
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ijms-16-01736-f003: AP7Glu improved pulmonary edema in vivo. Seventy-two hours after LPS injection with or without AP7Glu pretreatments, mice were exsanguinated and their right lower lungs were obtained. (A) The right lower lungs were used to assess wet to dry (W/D) ratio of lung; (B) Severity of lung injury was analyzed by the lung injury scoring system. Each value represents as mean ± SD of 6 mice. ### compared with sample of control group. **p < 0.01, and ***p < 0.001 were compared with LPS-alone group.

Mentions: As for the assessment of non-cardiogenic pulmonary edema, the ratio of the wet to dry weight (W/D) is another critical feature of ALI/ARDS. As shown in Figure 3A, the ameliorations in pulmonary edema are revealed in a dose-dependent manner. In detail, W/D ratio in the LPS group shows a remarkable difference compared with that in the control group. Otherwise, in Figure 3B, the lung injury score stands at around 4 points after LPS injection that is absolutely much higher than that in the other three groups with different amounts of AP7Glu, approximately the highest value only at 3 points. Meanwhile, it also presents a markedly downward trend in the lung injury score with gradually increases in the amount of AP7Glu intraperitoneal injection.


Apigenin-7-glycoside prevents LPS-induced acute lung injury via downregulation of oxidative enzyme expression and protein activation through inhibition of MAPK phosphorylation.

Li KC, Ho YL, Hsieh WT, Huang SS, Chang YS, Huang GJ - Int J Mol Sci (2015)

AP7Glu improved pulmonary edema in vivo. Seventy-two hours after LPS injection with or without AP7Glu pretreatments, mice were exsanguinated and their right lower lungs were obtained. (A) The right lower lungs were used to assess wet to dry (W/D) ratio of lung; (B) Severity of lung injury was analyzed by the lung injury scoring system. Each value represents as mean ± SD of 6 mice. ### compared with sample of control group. **p < 0.01, and ***p < 0.001 were compared with LPS-alone group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307331&req=5

ijms-16-01736-f003: AP7Glu improved pulmonary edema in vivo. Seventy-two hours after LPS injection with or without AP7Glu pretreatments, mice were exsanguinated and their right lower lungs were obtained. (A) The right lower lungs were used to assess wet to dry (W/D) ratio of lung; (B) Severity of lung injury was analyzed by the lung injury scoring system. Each value represents as mean ± SD of 6 mice. ### compared with sample of control group. **p < 0.01, and ***p < 0.001 were compared with LPS-alone group.
Mentions: As for the assessment of non-cardiogenic pulmonary edema, the ratio of the wet to dry weight (W/D) is another critical feature of ALI/ARDS. As shown in Figure 3A, the ameliorations in pulmonary edema are revealed in a dose-dependent manner. In detail, W/D ratio in the LPS group shows a remarkable difference compared with that in the control group. Otherwise, in Figure 3B, the lung injury score stands at around 4 points after LPS injection that is absolutely much higher than that in the other three groups with different amounts of AP7Glu, approximately the highest value only at 3 points. Meanwhile, it also presents a markedly downward trend in the lung injury score with gradually increases in the amount of AP7Glu intraperitoneal injection.

Bottom Line: Additionally, inflammation, which can decrease the activities of antioxidative enzymes (AOEs) is also observed in these studies.At the same time, flavonoids are reported to promote the activities of heme oxygenase-1 (HO-1) decreased by LPS.Meanwhile, our data revealed that AP7Glu not only did significantly inhibit the LPS-enhanced inflammatory activity in lung, but also exhibited anti-inflammatory effect through the MAPK and inhibitor NF-κB (IκB) pathways.

View Article: PubMed Central - PubMed

Affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Pharmacy, China Medical University, Taichung 404, Taiwan. u9852852@cmu.edu.tw.

ABSTRACT
Apigenin-7-glycoside (AP7Glu) with multiple biological activities is a flavonoid that is currently prescribed to treat inflammatory diseases such as upper respiratory infections. Recently, several studies have shown that its anti-inflammatory activities have been strongly linked to the inhibition of secretion of pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOs) and cyclooxygenase-2 (COX-2) induced through phosphorylation nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPK) pathways. Additionally, inflammation, which can decrease the activities of antioxidative enzymes (AOEs) is also observed in these studies. At the same time, flavonoids are reported to promote the activities of heme oxygenase-1 (HO-1) decreased by LPS. The purpose of this study was to assess these theories in a series of experiments on the suppressive effects of AP7Glu based on LPS-induced nitric oxide production in RAW264.7 macrophages in vitro and acute lung injury in mice in vivo. After six hours of lipopolysaccharide (LPS) stimulation, pulmonary pathological, myeloperoxidase (MPO) activity, total polymorphonuclear leukocytes (PMN) cells, cytokines in bronchoalveolar lavage fluid (BALF) and AOEs, are all affected and changed. Meanwhile, our data revealed that AP7Glu not only did significantly inhibit the LPS-enhanced inflammatory activity in lung, but also exhibited anti-inflammatory effect through the MAPK and inhibitor NF-κB (IκB) pathways.

Show MeSH
Related in: MedlinePlus