Kaempferol regulates MAPKs and NF-κB signaling pathways to attenuate LPS-induced acute lung injury in mice

Chen, Xiaojun; Yang, Xiaofeng; Liu, Tianjiao; Guan, Mingzhi; Feng, Xiangru; Dong, Wei; Chu, Xiao; Liu, Jing; Tian, Xianzhong; Ci, Xinxin; Li, Hongyu; Wei, Jiangtao; Deng, Yong; Deng, Xuming; Chi, Gefu; Sun, Zhi-Liang

doi:10.1016/j.intimp.2012.07.007

Cited by 158 publications

(93 citation statements)

References 45 publications

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“…As an important nuclear transcription factor, NF-κB is the intersection of multiple signaling pathways (28). A number of studies have found that the activation of NF-κB that occurs in ARDS may cause inflammatory cytokines, including adhesion molecules (CD11b/CD18, ICAM-1), chemokines (IL-8), TNF-α and IL-1β, to be expressed at the maximum level, which involves the transcriptional regulation of the activation of numerous genes (8,29).…”

Section: Discussionmentioning

confidence: 99%

Regulatory mechanism of pyrrolidine dithiocarbamate is mediated by nuclear factor-κB and inhibits neutrophil accumulation in ARDS mice

Wang

Zhao

et al. 2014

Experimental and Therapeutic Medicine

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The aim of the present study was to investigate the regulatory mechanism of nuclear factor (NF)-κB on polymorphonuclear neutrophil (PMN) accumulation and the inflammatory response in lung tissues with acute respiratory distress syndrome (ARDS), as well as the therapeutic effect of pyrrolidine dithiocarbamate (PDTC). Mouse models of ARDS were established by intraperitoneal injection of lipopolysaccharide (LPS). BALB/c mice were divided into control, LPS and PDTC + LPS groups. The expression of PMN adhesion molecules, CD11b/CD18 and intercellular adhesion molecule-1 (ICAM-1), were detected by immunohistochemistry, while the protein expression levels of NF-κB p65 in the lung tissue were analyzed by western blot analysis. In addition, flow cytometry was used to investigate the apoptosis rate of PMNs in the bronchoalveolar fluid, and the expression levels of interleukin (IL)-1β, IL-8 and tumor necrosis factor (TNF)-α and myeloperoxidase (MPO) activity were also determined. Following an intraperitoneal injection of LPS, alveolar septum rupture, pulmonary interstitial hyperemia and PMN infiltration in the alveolar was observed. The protein expression of p65 in the pulmonary cytoplasm decreased, while the expression of p65 in the nucleus increased. The levels of IL-8, IL-1β and TNF-α increased and the high expression status was maintained for 24 h. As the time increased, CD11b/CD18 and ICAM-1 expression increased, as well as MPO activity, while the apoptosis of PMNs was delayed. Compared with the LPS group, the expression of p65 in the pulmonary cytoplasm and the PMN apoptosis rate increased following PDTC intervention, while the expression of p65 in the nucleus decreased, as well as the expression levels of the cytokines and MPO activity. Therefore, PDTC reduced the production of inflammatory cytokines via the NF-κB pathway, which reduced the activation of PMNs in the lung tissue and promoted PMN apoptosis.

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Section: Discussionmentioning

confidence: 99%

Regulatory mechanism of pyrrolidine dithiocarbamate is mediated by nuclear factor-κB and inhibits neutrophil accumulation in ARDS mice

Wang

Zhao

et al. 2014

Experimental and Therapeutic Medicine

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“…BALF was collected as previously described (20). In brief, after the animals were sacrificed, the BALF was obtained by intratracheal intubation.…”

Section: Animals and Groupsmentioning

confidence: 99%

Naringenin ameliorates LPS-induced acute lung injury through its anti-oxidative and anti-inflammatory activity and by inhibition of the PI3K/AKT pathway

Zhao¹,

Shen

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to explore the effect of naringenin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a mouse model, as well as the underlying mechanism. The animals were randomly assigned to four groups: PBS-treated healthy control (Control), LPS-induced ALI (LPS), vehicle-treated ALI (LPS + Vehicle), and naringenin-treated ALI (LPS + Nar) group. Naringenin (100 mg/kg) was administered orally for 4 consecutive days, starting 3 days prior to induction of ALI. The survival rates of mice, lung wet/dry weight ratios, lung injury score, protein levels of bronchoalveolar lavage fluid (BALF), lactate dehydrogenase (LDH) activity in the BALF, lung myeloperoxidase (MPO) activity, the number of infiltrated neutrophils and reactive oxygen species (ROS) levels (H 2 O 2 and malondialdehyde) were assessed. In addition, the serum and BALF levels of inflammatory cytokines [tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and macrophage inflammatory protein 2] were determined, along with the total and the phosphorylated protein levels of phosphatidylinositol 3-hydroxy kinase (PI3K) and AKT in lung tissues. The results showed that naringenin pre-treatment significantly increased the survival rate, improved histopathologic changes, alleviated pulmonary edema and lung vascular leak, downregulated the levels of ROS and reduced neutrophil infiltration as well as the levels of inflammatory cytokines in the serum and BALF. Moreover, naringenin pre-treatment reduced the total and the phosphorylated protein levels of PI3K and AKT. The present study suggested that naringenin pre-treatment ameliorated LPS-induced ALI through its anti-oxidative and anti-inflammatory activity and by inhibition of the PI3K/AKT pathway in mice.

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“…Through histological studies was possible to find that this flavonol substantially attenuated alveolar wall thickness and hemorrhage as well as inflammatory cells infiltration in lung parenchyma induced by LPS; however, superoxide dismutase activity increased. It was suggested that the mechanism of kaempferol's (12) benefic effect in LPS-induced ARDS was via the controlling of the MAPK and NF-B signaling pathways, with inhibition of tissue oxidative stress and pulmonary inflammatory response most likely involved as well [100]. Acting on toll-like receptor 4 (TLR4), a < 20 μM concentration of nontoxic kaempferol (12) attenuated the LPS-induced IL-8 release and inhibited eotaxin-1 induction as well [101] The flavanone pinocembrin (10) has been assessed for its therapeutic effects in LPS-induced ARDS.…”

Section: Acute Respiratory Distress Syndrome (Ards)mentioning

confidence: 99%

Structure-Activity Association of Flavonoids in Lung Diseases

et al. 2014

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Flavonoids are polyphenolic compounds classified into flavonols, flavones, flavanones, isoflavones, catechins, anthocyanidins, and chalcones according to their chemical structures. They are abundantly found in Nature and over 8,000 flavonoids have from different sources, mainly plant materials, have been described. Recently reports have shown the valuable effects of flavonoids as antiviral, anti-allergic, antiplatelet, antitumor, antioxidant, and anti-inflammatory agents and interest in these compounds has been increasing since they can be helpful to human health. Several mechanisms of action are involved in the biological properties of flavonoids such as free radical scavenging, transition metal ion chelation, activation of survival genes and signaling pathways, regulation of mitochondrial function and modulation of inflammatory responses. The anti-inflammatory effects of flavonoids have been described in a number of studies in the literature, but not frequently associated to respiratory disease. Thus, this review aims to discuss the effects of different flavonoids in the control of lung inflammation in some disorders such as asthma, lung emphysema and acute respiratory distress syndrome and the possible mechanisms of action, as well as establish some structure-activity relationships between this biological potential and chemical profile of these compounds.

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Kaempferol regulates MAPKs and NF-κB signaling pathways to attenuate LPS-induced acute lung injury in mice

Cited by 158 publications

References 45 publications

Regulatory mechanism of pyrrolidine dithiocarbamate is mediated by nuclear factor-κB and inhibits neutrophil accumulation in ARDS mice

Regulatory mechanism of pyrrolidine dithiocarbamate is mediated by nuclear factor-κB and inhibits neutrophil accumulation in ARDS mice

Naringenin ameliorates LPS-induced acute lung injury through its anti-oxidative and anti-inflammatory activity and by inhibition of the PI3K/AKT pathway

Structure-Activity Association of Flavonoids in Lung Diseases

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