Apigenin Reduces NF-κB and Subsequent Cytokine Production as Protective Effect in a Rodent Animal Model of Lung Ischemia-Reperfusion Injury

Bougioukas, Ioannis; Didilis, Vassilios; Emmert, Alexander; Jebran, Ahmad Fawad; Waldmann-Beushausen, Regina; Stojanović, Tomislav; Schoendube, Friedrich A.; Danner, Bernhard C.

doi:10.1080/08941939.2017.1296512

Cited by 8 publications

(8 citation statements)

References 25 publications

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“…Chronic vascular inflammation is closely related to AS development [36]. Previous studies have revealed that apigenin can protect against inflammation [22,23]. Thus, we examined the effects of apigenin on LPS-stimulated inflammation in RAW264.7 macrophages.…”

Section: Apigenin Inhibits the Activation Of Tlr-4/nf-κb Pathway In Mmentioning

confidence: 99%

“…Notably, apigenin can ameliorate inflammation through inhibition of TLR-4 and NF-κB activation. In a mouse model of lung ischemia-reperfusion injury (LIRI), apigenin administration significantly reduced NF-κB activation and the expression levels of tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6), and inducible nitric oxide synthase (iNOS) [22]. Zhang et al [23] demonstrated that apigenin could improve early brain injury (EBI) and protect against blood-brain barrier (BBB) disruption in subarachnoid hemorrhage rats by repressing TLR-4/NF-κB pathway-mediated inflammation.…”

Section: Introductionmentioning

confidence: 99%

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Apigenin Retards Atherogenesis by Promoting ABCA1-Mediated Cholesterol Efflux and Suppressing Inflammation

Ren

Jiang

Zhou

et al. 2018

Cell Physiol Biochem

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Background/Aims: The development of atherosclerosis is accompanied by escalating inflammation and lipid accumulation within blood vessel walls. ABCA1 plays a crucial role in mediating cholesterol efflux from macrophages, which protects against atherogenesis. This research was designed to explore the effects and underlying mechanisms of apigenin (4’, 5, 7-trihydroxyflavone) on ABCA1-mediated cellular cholesterol efflux and LPS-stimulated inflammation in RAW264.7 macrophages and apoE^-/- mice. Methods: Expression of genes or proteins was examined by RT-PCR or western blot analysis. Liquid scintillation counting was used to detect percent cholesterol efflux. Cellular cholesterol content was measured using HPLC assay. The secretion levels of pro-inflammatory cytokines were quantified by ELISA assay. Atherosclerotic lesion sizes were determined with Oil Red O staining. The contents of macrophages and smooth muscle cells in atherosclerotic lesion were evaluated using immunohistochemistry. Plasma TC, TG, HDL-C and LDL-C levels in apoE^-/- mice were evaluated using commercial test kits. Results: Apigenin potently increased ABCA1 expression through miR-33 repression in a dose- and time-dependent manner. Treatment with apigenin significantly increased ABCA1-mediated cholesterol efflux, and reduced TC, FC and CE levels in macrophage-derived foam cells. In LPS-treated macrophages, the expression levels of TLR-4, MyD88 and p-IκB-α as well as nuclear NF-κB p65 were decreased by the addition of apigenin. Moreover, apigenin markedly decreased secretion levels of several pro-inflammatory cytokines. Lastly, in LPS-challenged apoE^-/- mice, apigenin administration augmented ABCA1 expression, decreased the contents of macrophages and smooth muscle cells in atherosclerotic lesion, reduced miR-33, TLR-4, and NF-κB p65 levels, improved plasma lipid profile and relieved inflammation, which results in less atherosclerotic lesion size. Conclusions: Taken together, these results suggest that apigenin may attenuate atherogenesis through up-regulating ABCA1-mediated cholesterol efflux and inhibiting inflammation.

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Section: Apigenin Inhibits the Activation Of Tlr-4/nf-κb Pathway In Mmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Apigenin Retards Atherogenesis by Promoting ABCA1-Mediated Cholesterol Efflux and Suppressing Inflammation

Ren

Jiang

Zhou

et al. 2018

Cell Physiol Biochem

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“…Both the cyclic stretch and hepatic ischemia-reperfusion-induced HMGB1 expression were mediated through NF- κ B signalling pathways [ 27 , 28 ]. Other research has confirmed that pulmonary I/R injury can lead to NF- κ B activation [ 29 , 30 ]. Notably, TLR4 directly activates NF- κ B signalling pathways and the expression of proinflammatory cytokines such as IL-1 β and TNF- α [ 31 ].…”

Section: Discussionmentioning

confidence: 94%

Cardiopulmonary Bypass Induces Acute Lung Injury via the High-Mobility Group Box 1/Toll-Like Receptor 4 Pathway

Deng

Hou

et al. 2020

Disease Markers

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During cardiopulmonary bypass (CPB), pulmonary ischemia/reperfusion (I/R) injury can cause acute lung injury (ALI). Our previous research confirmed that abnormal high-mobility group box 1 (HMGB1) release after CPB was closely related to ALI. However, the mechanism underlying the HMGB1-mediated induction of ALI after CPB is unclear. Our previous study found that HMGB1 binds Toll-like receptor 4 (TLR4), leading to lung injury, but direct evidence of a role for these proteins in the mechanism of CPB-induced lung injury has not been shown. We examined the effects of inhibiting HMGB1 or reducing TLR4 expression on CPB-induced lung injury in rats administered anti-HMBG1 antibody or TLR4 short-hairpin RNA (shTLR4), respectively. In these rat lungs, we studied the histologic changes and levels of interleukin- (IL-) 1β, tumour necrosis factor- (TNF-) α, HMGB1, and TLR4 after CPB. After CPB, the lung tissues from untreated rats showed histologic features of injury and significantly elevated levels of IL-1β, TNF-α, HMGB1, and TLR4. Treatment with anti-HMGB1 attenuated the CPB-induced morphological inflammatory response and protein levels of IL-1β, TNF-α, HMGB1, and TLR4 in the lung tissues and eventually alleviated the ALI after CPB. Treatment with shTLR4 attenuated the CPB-induced morphological inflammatory response and protein levels of IL-1β, TNF-α, and TLR4 in the lung tissues and eventually alleviated the ALI after CPB, but could not alleviate the HMGB1 protein levels induced by CPB. In summary, the present study demonstrated that the HMGB1/TLR4 pathway mediated the development of ALI induced by CPB.

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“…Nrf2 has been shown to be an important transcription factor induced by the antioxidant response [10]. Nrf2 could activate a battery of antioxidant genes, HO-1, NQO1 and other genes, which regulated oxidative stress, inflammatory reactions and apoptosis in various disorders [12, 38, 39]. Furthermore, NF-κB is also an important transcription factor that plays an important role in redox changes [14].…”

Section: Discussionmentioning

confidence: 99%

“…It has also been proven that Nrf2 is an essential cytoprotective regulator considering genes encoding the expression of proteins of antioxidants, detoxification enzymes, and other mediators of stress response [11]. These genes confer the resistance to oxidative stress in various disorders, including catalase (CAT), superoxide dismutase (SOD), Glutathione S-transferase (GST), NADPH quinine oxidoreductase-1 (NQO1) and heme oxygenase-1 (HO-1) [12, 13]. In addition, nuclear factor kappa B (NF-κB), which can be activated by ROS in I/R injury, is one of the major redox-sensitive transcription factors controlling the expression of pro-inflammatory genes [14].…”

Section: Introductionmentioning

confidence: 99%

Zinc-induced protective effect for testicular ischemia-reperfusion injury by promoting antioxidation via microRNA-101-3p/Nrf2 pathway

Qin

Zhu

Xue

et al. 2019

Aging

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The present study was performed to determine the protective effect of Zinc on the rat testicular ischemia-reperfusion (I/R) injury and its mechanism. In vivo, the pathological changes and the apoptosis index were significantly relieved in the rats with Low-dose Zinc pretreatment, compared to the I/R group. After Low-dose Zinc treatment, the levels of tissue Malondialdehyde (MDA) were significantly decreased, while tissue antioxidant indices were significantly increased. Meanwhile, the level of NF-κB was significantly lower compared to I/R group, while the levels of Nrf2-dependent antioxidant enzymes were significantly higher in Low-dose Zinc+I/R group. In vitro, Low-dose Zinc markedly increased Leydig cell (TM3) cell viability, and relieved testicular oxidative damage via down-regulating ROS. A total of 22 differently expressed microRNAs were screened out using microRNA microarray in rat testicular tissue caused by I/R injury, especially showing that miR-101-3p was selected as the target miRNA. Furthermore, the levels of Nrf2 and NF-κB were apparently increased/decreased in TM3 cells treated with Hypoxic/Reoxygenation (H/R) after miR-101-3p mimics/inhibitor. In addition, H/R-induced testicular oxidative damage was recovered in TM3 administrated with miR-101-3p inhibitor and si-Nrf2. Therefore, this study provided a novel insight for investigating protective effect of Zinc on testicular I/R injury by promoting antioxidation via miR-101-3p/Nrf2.

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Apigenin Reduces NF-κB and Subsequent Cytokine Production as Protective Effect in a Rodent Animal Model of Lung Ischemia-Reperfusion Injury

Abstract: We conclude that apigenin given intraperitoneally can reduce activation of NF-κB and also attenuate the expression of TNFα, IL-6, and iNOS in a surgical model of LIRI. The surgical procedure itself can induce significant damage to the lungs.

Cited by 8 publications

References 25 publications

Apigenin Retards Atherogenesis by Promoting ABCA1-Mediated Cholesterol Efflux and Suppressing Inflammation

Apigenin Retards Atherogenesis by Promoting ABCA1-Mediated Cholesterol Efflux and Suppressing Inflammation

Cardiopulmonary Bypass Induces Acute Lung Injury via the High-Mobility Group Box 1/Toll-Like Receptor 4 Pathway

Zinc-induced protective effect for testicular ischemia-reperfusion injury by promoting antioxidation via microRNA-101-3p/Nrf2 pathway

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