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Icariin ameliorates cigarette smoke induced inflammatory responses via suppression of NF-κB and modulation of GR in vivo and in vitro.

Li L, Sun J, Xu C, Zhang H, Wu J, Liu B, Dong J - PLoS ONE (2014)

Bottom Line: We found that icariin significantly protected pulmonary function and attenuated CS-induced inflammatory response by decreasing inflammatory cells and production of TNF-α, IL-8 and MMP-9 in both the serum and BALF of CS-exposed mice and decreasing production of TNF-α and IL-8 in the supernatant of CSE-exposed A549 cells.Icariin also showed properties in inhibiting the phosphorylation of NF-κB p65 protein and blocking the degradation of IΚB-α protein.Together these results suggest that icariin has anti-inflammatory effects in cigarette smoke induced inflammatory models in vivo and in vitro, possibly achieved by suppressing NF-κB activation and modulating GR protein expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrated Traditional Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai, China.

ABSTRACT

Purpose: To investigate the effects of icariin, a major constituent of flavonoids isolated from the herb Epimedium, on cigarette smoke (CS) induced inflammatory responses in vivo and in vitro.

Methods: In vivo, BALB/c mice were exposed to smoke of 15 cigarettes for 1 h/day, 6 days/week for 3 months and dosed with icariin (25, 50 and 100 mg/kg) or dexamethasone (1 mg/kg). In vitro, A549 cells were incubated with icariin (10, 50 and 100 µM) followed by treatments with CSE (2.5%).

Results: We found that icariin significantly protected pulmonary function and attenuated CS-induced inflammatory response by decreasing inflammatory cells and production of TNF-α, IL-8 and MMP-9 in both the serum and BALF of CS-exposed mice and decreasing production of TNF-α and IL-8 in the supernatant of CSE-exposed A549 cells. Icariin also showed properties in inhibiting the phosphorylation of NF-κB p65 protein and blocking the degradation of IΚB-α protein. Further studies revealed that icariin administration markedly restore CS-reduced GR protein and mRNA expression, which might subsequently contribute to the attenuation of CS-induced respiratory inflammatory response.

Conclusion: Together these results suggest that icariin has anti-inflammatory effects in cigarette smoke induced inflammatory models in vivo and in vitro, possibly achieved by suppressing NF-κB activation and modulating GR protein expression.

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Chemical structure of icariin.(molecular formula: C33H40O15; molecular weight: 676.67).
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pone-0102345-g001: Chemical structure of icariin.(molecular formula: C33H40O15; molecular weight: 676.67).

Mentions: Icariin (Fig. 1), a major constituent of flavonoids isolated from the herb Epimedium, has been confirmed to exert the effects of anti-inflammation, anticancer, cardiovascular protection and bone formation promotion [14], [15]. Our studies have demonstrated that icariin and its derivative, 3,5,7-trihydroxy-4′-methoxy-8- (3-hydroxy-3-methylbutyl)-flavone(ICT), attenuates lipopolysaccharide (LPS)- induced inflammatory response mouse models of inflammation and in murine macrophage cell lines, which involve down-regulation of IL-6 and TNF-α, as well as activation of the PI3K/Akt pathway and inhibition of NF-κB [16], [17]. Recently we reported that icariin attenuated social defeat-induced down-regulation of glucocorticoid receptor in a mouse model for depression by enhancing GR binding affinity and protein expression [18].


Icariin ameliorates cigarette smoke induced inflammatory responses via suppression of NF-κB and modulation of GR in vivo and in vitro.

Li L, Sun J, Xu C, Zhang H, Wu J, Liu B, Dong J - PLoS ONE (2014)

Chemical structure of icariin.(molecular formula: C33H40O15; molecular weight: 676.67).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4121073&req=5

pone-0102345-g001: Chemical structure of icariin.(molecular formula: C33H40O15; molecular weight: 676.67).
Mentions: Icariin (Fig. 1), a major constituent of flavonoids isolated from the herb Epimedium, has been confirmed to exert the effects of anti-inflammation, anticancer, cardiovascular protection and bone formation promotion [14], [15]. Our studies have demonstrated that icariin and its derivative, 3,5,7-trihydroxy-4′-methoxy-8- (3-hydroxy-3-methylbutyl)-flavone(ICT), attenuates lipopolysaccharide (LPS)- induced inflammatory response mouse models of inflammation and in murine macrophage cell lines, which involve down-regulation of IL-6 and TNF-α, as well as activation of the PI3K/Akt pathway and inhibition of NF-κB [16], [17]. Recently we reported that icariin attenuated social defeat-induced down-regulation of glucocorticoid receptor in a mouse model for depression by enhancing GR binding affinity and protein expression [18].

Bottom Line: We found that icariin significantly protected pulmonary function and attenuated CS-induced inflammatory response by decreasing inflammatory cells and production of TNF-α, IL-8 and MMP-9 in both the serum and BALF of CS-exposed mice and decreasing production of TNF-α and IL-8 in the supernatant of CSE-exposed A549 cells.Icariin also showed properties in inhibiting the phosphorylation of NF-κB p65 protein and blocking the degradation of IΚB-α protein.Together these results suggest that icariin has anti-inflammatory effects in cigarette smoke induced inflammatory models in vivo and in vitro, possibly achieved by suppressing NF-κB activation and modulating GR protein expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Integrated Traditional Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai, China.

ABSTRACT

Purpose: To investigate the effects of icariin, a major constituent of flavonoids isolated from the herb Epimedium, on cigarette smoke (CS) induced inflammatory responses in vivo and in vitro.

Methods: In vivo, BALB/c mice were exposed to smoke of 15 cigarettes for 1 h/day, 6 days/week for 3 months and dosed with icariin (25, 50 and 100 mg/kg) or dexamethasone (1 mg/kg). In vitro, A549 cells were incubated with icariin (10, 50 and 100 µM) followed by treatments with CSE (2.5%).

Results: We found that icariin significantly protected pulmonary function and attenuated CS-induced inflammatory response by decreasing inflammatory cells and production of TNF-α, IL-8 and MMP-9 in both the serum and BALF of CS-exposed mice and decreasing production of TNF-α and IL-8 in the supernatant of CSE-exposed A549 cells. Icariin also showed properties in inhibiting the phosphorylation of NF-κB p65 protein and blocking the degradation of IΚB-α protein. Further studies revealed that icariin administration markedly restore CS-reduced GR protein and mRNA expression, which might subsequently contribute to the attenuation of CS-induced respiratory inflammatory response.

Conclusion: Together these results suggest that icariin has anti-inflammatory effects in cigarette smoke induced inflammatory models in vivo and in vitro, possibly achieved by suppressing NF-κB activation and modulating GR protein expression.

Show MeSH
Related in: MedlinePlus