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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 attenuated pulmonary inflammation in vivo. Seventy-two hours after LPS injection with or without AP7Glu pretreatments, mice were exsanguinated and their left lower lungs were fixed. Then, tissue sections were stained with hematoxylin and eosin (H&E). The figure demonstrates a representative view (×200) from each group; each bar represents the mean ± SD of 6 mice. (A) Control; (B) LPS; (C) LPS + Dex; (D) LPS + AP7Glu-H; (E) LPS + AP7Glu-M; (F) LPS + AP7Glu-L. The infiltrating neutrophils were more abundant in (B) LPS group as shown by arrows.
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ijms-16-01736-f002: AP7Glu attenuated pulmonary inflammation in vivo. Seventy-two hours after LPS injection with or without AP7Glu pretreatments, mice were exsanguinated and their left lower lungs were fixed. Then, tissue sections were stained with hematoxylin and eosin (H&E). The figure demonstrates a representative view (×200) from each group; each bar represents the mean ± SD of 6 mice. (A) Control; (B) LPS; (C) LPS + Dex; (D) LPS + AP7Glu-H; (E) LPS + AP7Glu-M; (F) LPS + AP7Glu-L. The infiltrating neutrophils were more abundant in (B) LPS group as shown by arrows.

Mentions: In an attempt to assess the pathological changes, HE staining was used in our study. After the sacrifice of mice, lung tissue sections were soaked in formalin for two days before histological evaluation. Figure 2B reveals the results in a series of images of notable inflammatory neutrophil infiltration, interstitial edema, interalveolar septal thickening, and intraalveolar and interstitial patchy hemorrhage. However, after treatments of AP7Glu and Dex, the pathological changes in lung tissues are relieved (Figure 2C–E). In contrast to the LPS only group, no evidence of lung injury is found in the normal control group (Figure 2A).


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 attenuated pulmonary inflammation in vivo. Seventy-two hours after LPS injection with or without AP7Glu pretreatments, mice were exsanguinated and their left lower lungs were fixed. Then, tissue sections were stained with hematoxylin and eosin (H&E). The figure demonstrates a representative view (×200) from each group; each bar represents the mean ± SD of 6 mice. (A) Control; (B) LPS; (C) LPS + Dex; (D) LPS + AP7Glu-H; (E) LPS + AP7Glu-M; (F) LPS + AP7Glu-L. The infiltrating neutrophils were more abundant in (B) LPS group as shown by arrows.
© Copyright Policy
Related In: Results  -  Collection

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

ijms-16-01736-f002: AP7Glu attenuated pulmonary inflammation in vivo. Seventy-two hours after LPS injection with or without AP7Glu pretreatments, mice were exsanguinated and their left lower lungs were fixed. Then, tissue sections were stained with hematoxylin and eosin (H&E). The figure demonstrates a representative view (×200) from each group; each bar represents the mean ± SD of 6 mice. (A) Control; (B) LPS; (C) LPS + Dex; (D) LPS + AP7Glu-H; (E) LPS + AP7Glu-M; (F) LPS + AP7Glu-L. The infiltrating neutrophils were more abundant in (B) LPS group as shown by arrows.
Mentions: In an attempt to assess the pathological changes, HE staining was used in our study. After the sacrifice of mice, lung tissue sections were soaked in formalin for two days before histological evaluation. Figure 2B reveals the results in a series of images of notable inflammatory neutrophil infiltration, interstitial edema, interalveolar septal thickening, and intraalveolar and interstitial patchy hemorrhage. However, after treatments of AP7Glu and Dex, the pathological changes in lung tissues are relieved (Figure 2C–E). In contrast to the LPS only group, no evidence of lung injury is found in the normal control group (Figure 2A).

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