Geraniin attenuates LPS-induced acute lung injury via inhibiting NF-κB and activating Nrf2 signaling pathways

Zhu, Guangfa; Xin, Xi; Liu, Yan; Huang, Yan; Keng, Li‐Ta; Wu, Canrong

doi:10.18632/oncotarget.15227

Cited by 41 publications

(27 citation statements)

References 33 publications

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“…Our data show a significant increase in the expression of Nrf2 in lung homogenate of mice treated with adenine suggesting that adenine treatment could trigger adaptive responses that counterbalance the potentially damaging activity of oxygen radicals induced by adenine administration. Our data corroborate the finding of a recent study which showed that Nrf2 expression is increased in lipopolysaccharide (LPS)-induced lung injury in mice (Zhu et al, 2017 ). In the same study, it was shown that geraniin, an ellagitannin isolated from Phyllanthusurinaria Linnnatural which has anti-inflammatory and antioxidant actions, inhibited NF-κB activation and induced an up-regulation of Nrf2 expression that resulted in the attenuated LPS-induced acute lung injury (Zhu et al, 2017 ).…”

Section: Discussionsupporting

confidence: 92%

Lung Oxidative Stress, DNA Damage, Apoptosis, and Fibrosis in Adenine-Induced Chronic Kidney Disease in Mice

et al. 2017

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It is well-established that there is a crosstalk between the lung and the kidney, and several studies have reported association between chronic kidney disease (CKD) and pulmonary pathophysiological changes. Experimentally, CKD can be caused in mice by dietary intake of adenine. Nevertheless, the consequence of such intervention on the lung received only scant attention. Here, we assessed the pulmonary effects of adenine (0.2% w/w in feed for 4 weeks)-induced CKD in mice by assessing various physiological histological and biochemical endpoints. Adenine treatment induced a significant increase in urine output, urea and creatinine concentrations, and it decreased the body weight and creatinine clearance. It also increased proteinuria and the urinary levels of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. Compared with control group, the histopathological evaluation of lungs from adenine-treated mice showed polymorphonuclear leukocytes infiltration in alveolar and bronchial walls, injury, and fibrosis. Moreover, adenine caused a significant increase in lung lipid peroxidation and reactive oxygen species and decreased the antioxidant catalase. Adenine also induced DNA damage assessed by COMET assay. Similarly, adenine caused apoptosis in the lung characterized by a significant increase of cleaved caspase-3. Moreover, adenine induced a significant increase in the expression of nuclear factor erythroid 2–related factor 2 (Nrf2) in the lung. We conclude that administration of adenine in mice induced CKD is accompanied by lung oxidative stress, DNA damage, apoptosis, and Nrf2 expression and fibrosis.

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Section: Discussionsupporting

confidence: 92%

Lung Oxidative Stress, DNA Damage, Apoptosis, and Fibrosis in Adenine-Induced Chronic Kidney Disease in Mice

et al. 2017

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“…2A) with febuxostat treatment, we searched for other potential sources of ROS. As LPS leads to an influx of inflammatory cells, that is, neutrophils (Zhu et al 2017), we measured myeloperoxidase activity as marker of neutrophil-generated ROS. As shown in Figure 2 Xanthine Oxidoreductase, there is marked increase in myeloperoxidase activity after LPS exposure.…”

Section: Inhibiting Xor With Febuxostat Does Not Improve Lipopolysaccmentioning

confidence: 99%

XOR inhibition with febuxostat accelerates pulmonary endothelial barrier recovery and improves survival in lipopolysaccharide-induced murine sepsis

et al. 2017

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Sepsis is a leading cause of death among patients in the intensive care unit, resulting from multi‐organ failure. Activity of xanthine oxidoreductase (XOR), a reactive oxygen species (ROS) producing enzyme, is known to be elevated in nonsurvivors of sepsis compared to survivors. We have previously demonstrated that XOR is critical for ventilator‐induced lung injury. Using febuxostat, a novel nonpurine inhibitor of XOR, we sought to determine the role of XOR inhibition in a murine model of sepsis‐induced lung injury and mortality. C57BL/6J mice were subjected to intravenous (IV) lipopolysaccharide (LPS) for various time points, and lungs were harvested for analyses. Subsets of mice were treated with febuxostat, pre or post LPS exposure, or vehicle. Separate groups of mice were followed up for mortality after LPS exposure. After 24 hr of IV LPS , mice exhibited an increase in XOR activity in lung tissue and a significant increase in pulmonary endothelial barrier disruption. Pretreatment of animals with febuxostat before exposure to LPS, or treatment 4 h after LPS, resulted in complete abrogation of XOR activity. Inhibition of XOR with febuxostat did not prevent LPS‐induced pulmonary vascular permeability at 24 h, however, it accelerated recovery of the pulmonary endothelial barrier integrity in response to LPS exposure. Furthermore, treatment with febuxostat resulted in significant reduction in mortality. Inhibition of XOR with febuxostat accelerates recovery of the pulmonary endothelial barrier and prevents LPS‐induced mortality, whether given before or after exposure to LPS.

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“…Geraniin, the main polyphenolic compound of geraniums [11,13], was first isolated from Geranium thunbergii [14]. The beneficial effects of geraniin, including antiinflammatory and anti-cancer effects in LPS-induced macrophages by inhibiting NF-κB and Nrf2 signaling pathways, as well as its antioxidant activities, have been reported [14][15][16]. However, the ameliorating effects of geraniin on esophageal damages in RE via anti-inflammatory activities have not been reported.…”

Section: Introductionmentioning

confidence: 99%

Geraniin ameliorate experimental acute reflux esophagitis via NF-κB regulated anti-inflammatory activities in rats

Nam

Park

et al. 2019

Appl Biol Chem

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Repeated reflux of gastric acid and stomach contents into the esophagus leads to esophagus damage, including inflammation, ulcer, and hemorrhage in the epithelium. In this study, we aimed to demonstrate the ameliorating effects of geraniin, a phytochemical in the geraniums, on esophagus damage in an acute reflux esophagitis (RE) rat model. The inflammatory effects of geraniinwas measured by nitric oxide (NO) production and pro-inflammatory protein levels in lipopolysaccharide (LPS)-induced RAW 264.7 cells. To evaluate the protective effects of geraniin on damaged esophagus tissue in RE rats, the rats were divided into the following groups: normal control; RE-induced control; RE rats pretreated with geraniin 15 and 30 mg/kg body weight; and RE rats pretreated with ranitidine 30 mg/ kg body weight as a positive control. The lesion area of esophagus was determined by the Image J program, and histological changes were examined by hematoxylin and eosin staining of rat esophageal tissue. The expression of proinflammatory proteins, cytokines, and tight junction proteins involved in esophagus damages was determined using western blotting of esophageal tissue. Geraniin revealed that anti-inflammatory effects against LPS-induced cells by significantly decreasing NO production and iNOS proteins level. Additionally, the results showed that improvement effects of geraniin on esophagus damages in RE induced rats. The expression of inflammatory proteins involved in nuclear factor NF-kB signaling pathways significantly decreased and tight junction protein (claudin-4 and claudin-5) was increased in esophageal tissue. We found the potential of geraniin as source of replacement therapy products source for inflammatory and reflux esophagitis disease.

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Geraniin attenuates LPS-induced acute lung injury via inhibiting NF-κB and activating Nrf2 signaling pathways

Cited by 41 publications

References 33 publications

Lung Oxidative Stress, DNA Damage, Apoptosis, and Fibrosis in Adenine-Induced Chronic Kidney Disease in Mice

Lung Oxidative Stress, DNA Damage, Apoptosis, and Fibrosis in Adenine-Induced Chronic Kidney Disease in Mice

XOR inhibition with febuxostat accelerates pulmonary endothelial barrier recovery and improves survival in lipopolysaccharide-induced murine sepsis

Geraniin ameliorate experimental acute reflux esophagitis via NF-κB regulated anti-inflammatory activities in rats

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