Apigenin Protects Endothelial Cells from Lipopolysaccharide (LPS)-Induced Inflammation by Decreasing Caspase-3 Activation and Modulating Mitochondrial Function

Duarte, Silvia; Arango, Daniel; Parihar, Arti; Hamel, Patrice; Yasmeen, Rumana; Doseff, Andrea I.

doi:10.3390/ijms140917664

Cited by 67 publications

(36 citation statements)

References 54 publications

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“…Apigenin has been shown to block lipopolysaccharide (LPS)-induced lethality in vivo and the expression of proinflammatory cytokines by inactivating NF-κB via the suppression of p65 phosphorylation (10). In endothelial cells, apigenin provides a protective effect against LPS-induced inflammation by decreasing caspase-3 activation and modulating mitochondrial function (11). Apigenin exerts anti-inflammatory activity via multiple mechanisms (12), including the induction of apoptosis and the regulation of MAPK signaling pathways in mouse macrophage ANA-1 cells (13).…”

Section: Discussionmentioning

confidence: 99%

Apigenin protects against bleomycin-induced lung fibrosis in rats

Chen

Zhao

2015

Experimental and Therapeutic Medicine

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Abstract. Apigenin is a non-toxic and non-mutagenic flavone that exists abundantly in numerous herbs and vegetables. Apigenin exerts anti-proliferative and anti-inflammatory properties. The aim of the present study was to investigate the effects of apigenin on bleomycin-induced lung fibrosis in rats. A single intratracheal instillation of bleomycin (5 mg/kg) was administered and rats were sacrificed on 7 and 28 days post bleomycin instillation. The instillation of bleomycin resulted in decreased body weight and an increase in the lung index. In addition, bleomycin administration increased the hydroxyproline content, myeloperoxidase (MPO) activity, tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β levels and decreased the superoxide dismutase (SOD) activity in the rat lung tissues. Excessive collagen deposits were detected in the lung tissues in bleomycin-treated rats compared with normal control rats. Notably, the oral administration of apigenin (10, 15 and 20 mg/kg/day) appeared to prevent the fibrotic process. The treatment suppressed the increases in hydroxyproline content, MPO activity, TNF-α and TGF-β levels and attenuated the reduction of SOD activity that were induced by bleomycin. Furthermore, excessive collagen deposition was inhibited by the apigenin treatment. Collectively, these results suggest that apigenin may function as a potent anti-inflammatory and anti-fibrotic agent against bleomycin-induced lung fibrosis.

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Section: Discussionmentioning

confidence: 99%

Apigenin protects against bleomycin-induced lung fibrosis in rats

Chen

Zhao

2015

Experimental and Therapeutic Medicine

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“…Targets of apigenin that could contribute to these anticancer activities include heat shock proteins (Osada et al 2004), fatty acid synthase (Brusselmans et al 2005), the aryl hydrocarbon receptor (Reiners et al 1999), HER2/neu (Way et al 2004), and matrix metalloproteinases (Kim 2003). Apigenin can also reduce markers of inflammation in response to lipopolysaccharides, TNF-α, and allergens and was shown to suppress activities of the inflammatory mediators cyclooxygenase and NF-κB (Liang et al 1999, Ruiz and Haller 2006, Li et al 2010, Kang et al 2011, Duarte et al 2013.…”

Section: Introductionmentioning

confidence: 99%

Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells

et al. 2017

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Apigenin (4′,5,7,-trihydroxyflavone) is a flavonoid found in certain herbs, fruits, and vegetables. Apigenin can attenuate inflammation, which is associated with many chronic diseases of aging. Senescent cellsstressed cells that accumulate with age in mammalsdisplay a pro-inflammatory senescence-associated secretory phenotype (SASP) that can drive or exacerbate several age-related pathologies, including cancer. Flavonoids, including apigenin, were recently shown to reduce the SASP of a human fibroblast strain induced to senesce by bleomycin. Here, we confirm that apigenin suppresses the SASP in three human fibroblast strains induced to senesce by ionizing radiation, constitutive MAPK (mitogen-activated protein kinase) signaling, oncogenic RAS, or replicative exhaustion. Apigenin suppressed the SASP in part by suppressing IL-1α signaling through IRAK1 and IRAK4, p38-MAPK, and NF-κB. Apigenin was particularly potent at suppressing the expression and secretion of CXCL10 (IP10), a newly identified SASP factor. Further, apigenin-mediated suppression of the SASP substantially reduced the aggressive phenotype of human breast cancer cells, as determined by cell proliferation, extracellular matrix invasion, and epithelialmesenchymal transition. Our results support the idea that apigenin is a promising natural product for reducing the impact of senescent cells on age-related diseases such as cancer.

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“…HG-BAEC were treated with nitrones for 24 h and then stained with 0.5 μM of JC-1for 30 min at 37 °C in the dark [27]. JC-1 dye intensity was quantified using BD LSR II flow cytometer (BD Biosciences, San Jose, CA, USA) by measuring emission at 520 nm and 590 nm.…”

Section: Methodsmentioning

confidence: 99%

Nitrones reverse hyperglycemia-induced endothelial dysfunction in bovine aortic endothelial cells

Headley

DiSilvestro

Bryant

et al. 2016

Biochemical Pharmacology

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Hyperglycemia has been implicated in the development of endothelial dysfunction through heightened ROS production. Since nitrones reverse eNOS dysfunction, increase antioxidant enzyme activity, and suppress pro-apoptotic signaling pathway and mitochondrial dysfunction from ROS-induced toxicity, the objective of this study was to determine whether nitrone spin traps DMPO, PBN and PBN-LA were effective at duplicating these effects and improving glucose uptake in an in vitro model of hyperglycemia-induced dysfunction using bovine aortic endothelial cells (BAEC). BAEC were cultured in DMEM medium with low (5.5 mM glucose, LG) or high glucose (50 mM, HG) for 14 days to model in vivo hyperglycemia as experienced in humans with metabolic disease. Improvements in cell viability, intracellular oxidative stress, NO and tetrahydrobiopterin levels, mitochondrial membrane potential, glucose transport, and activity of antioxidant enzymes were measured from single treatment of BAEC cells with nitrones for 24 h after hyperglycemia. Chronic hyperglycemia significantly increased intracellular ROS by 50%, decreased cell viability by 25%, reduced NO bioavailability by 50%, and decreased BH4 levels by 15% thereby decreasing NO production. Intracellular glucose transport and SOD activity were also decreased by 50% and 25% respectively. Nitrone (PBN and DMPO, 50 μM) treatment of BAEC cells grown in hyperglycemic conditions resulted in in the normalization of outcome measures except for SOD and catalase activities. Our findings demonstrate that the nitrones reverse the deleterious effects of hyperglycemia in BAEC cells. We believe that in vivo testing of these nitrone compounds in models of cardiometabolic disease is warranted.

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Apigenin Protects Endothelial Cells from Lipopolysaccharide (LPS)-Induced Inflammation by Decreasing Caspase-3 Activation and Modulating Mitochondrial Function

Cited by 67 publications

References 54 publications

Apigenin protects against bleomycin-induced lung fibrosis in rats

Apigenin protects against bleomycin-induced lung fibrosis in rats

Apigenin suppresses the senescence-associated secretory phenotype and paracrine effects on breast cancer cells

Nitrones reverse hyperglycemia-induced endothelial dysfunction in bovine aortic endothelial cells

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