Modulation of thioacetamide-induced hepatic inflammations, angiogenesis and fibrosis by andrographolide in mice

Lee, Tzung-Yan; Chang, Hen‐Hong; Wen, Chorng-Kai; Huang, Tse-Hung; Chang, Ya‐Shu

doi:10.1016/j.jep.2014.10.056

Cited by 46 publications

(26 citation statements)

References 39 publications

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“…3(F,G)], which further confirmed the role Nrf2/HO-1 plays in the inhibitory effects of andrographolide on hypoxia-induced HIF-1a targeted ET-1 gene expression and ET-1 secretion. These findings explain, at least in part, the anti-inflammatory, antiangiogenic, and anticarcinogenic properties of andrographolide (Lee et al, 2014;Li et al, 2015). Other phytochemicals have also been shown to inhibit ET-1 mRNA and protein expression as well as ET-1 secretion.…”

Section: Discussionmentioning

confidence: 82%

Andrographolide inhibits hypoxia-induced HIF-1α-driven endothelin 1 secretion by activating Nrf2/HO-1 and promoting the expression of prolyl hydroxylases 2/3 in human endothelial cells

Lin

et al. 2016

Environ. Toxicol.

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Andrographolide, the main bioactive component of the medicinal plant Andrographis paniculata, has been shown to possess potent anti-inflammatory activity. Endothelin 1 (ET-1), a potent vasoconstrictor peptide produced by vascular endothelial cells, displays proinflammatory property. Hypoxia-inducible factor 1α (HIF-1α), the regulatory member of the transcription factor heterodimer HIF-1α/β, is one of the most important molecules that responds to hypoxia. Changes in cellular HIF-1α protein level are the result of altered gene transcription and protein stability, with the latter being dependent on prolyl hydroxylases (PHDs). In this study, inhibition of pro-inflammatory ET-1 expression and changes of HIF-1α gene transcription and protein stability under hypoxia by andrographolide in EA.hy926 endothelial-like cells were investigated. Hypoxic conditions were created using the hypoxia-mimetic agent CoCl We found that hypoxia stimulated the production of reactive oxygen species (ROS), the expression of HIF-1α mRNA and protein, and the expression and secretion of ET-1. These effects, however, were attenuated by co-exposure to andrographolide, bilirubin, and RuCO. Silencing Nrf2 and heme oxygenase 1 (HO-1) reversed the inhibitory effects of andrographolide on hypxoia-induced HIF-1α mRNA and protein expression. Moreover, andrographolide increased the expression of prolyl hydroxylases (PHD) 2/3, which hydroxylate HIF-1α and promotes HIF-1α proteasome degradation, with an increase in HIF-1α hydroxylation was noted under hypoxia. Inhibition of p38 MAPK abrogated the hypoxia-induced increases in HIF-1α mRNA and protein expression as well as ET-1 mRNA expression and secretion. Taken together, these results suggest that andrographolide suppresses hypoxia-induced pro-inflammatory ET-1 expression by activating Nrf2/HO-1, inhibiting p38 MAPK signaling, and promoting PHD2/3 expression. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 918-930, 2017.

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Section: Discussionmentioning

confidence: 82%

Andrographolide inhibits hypoxia-induced HIF-1α-driven endothelin 1 secretion by activating Nrf2/HO-1 and promoting the expression of prolyl hydroxylases 2/3 in human endothelial cells

Lin

et al. 2016

Environ. Toxicol.

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“…42 Interestingly, some previous studies using TAA to induce CLD have also reported portal, portal-toportal bridging, or portal-to-central bridging fibrosis, as well as inflammatory cell accumulation in portal areas. 43e46 It is important to note that TAA induces severe morphologic changes in hepatic lobules, including irregular patterns of portal tracts and central veins, ductular reactions, and high vascularization directed to fibrotic areas, 45,47,48 providing a rich feeding ground for potential misinterpretation with regard to clear identification of portal as opposed to central areas. We cannot rule out that studies from other groups using TAA resulted in increased disease activity in periportal areas because results in experimental CLD greatly depend on the genetic background of the animals, concentration and administration route of the disease-inducing agent, and indeed the point in time of the experimental design.…”

Section: Discussionmentioning

confidence: 99%

Divergent Inflammatory, Fibrogenic, and Liver Progenitor Cell Dynamics in Two Common Mouse Models of Chronic Liver Injury

Köhn-Gaone

Dwyer

Grzelak

et al. 2016

The American Journal of Pathology

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Complications of end-stage chronic liver disease signify a major cause of mortality worldwide. Irrespective of the underlying cause, most chronic liver diseases are characterized by hepatocellular necrosis, inflammation, fibrosis, and proliferation of liver progenitor cells or ductular reactions. Vast differences exist between experimental models that mimic these processes, and their identification is fundamental for translational research. We compared two common murine models of chronic liver disease: the choline-deficient, ethionine-supplemented (CDE) diet versus thioacetamide (TAA) supplementation. Markers of liver injury, including serum alanine transaminase levels, apoptosis, hepatic fat loading, and oxidative stress, as well as inflammatory, fibrogenic and liver progenitor cell responses, were assessed at days 3, 7, 14, 21, and 42. This study revealed remarkable differences between the models. It identified periportal injury and fibrosis with an early peak and slow normalization of all parameters in the CDE regimen, whereas TAA-treated mice had pericentral patterns of progressive injury and fibrosis, resulting in a more severe hepatic injury phenotype. This study is the first to resolve two different patterns of injury and fibrosis in the CDE and TAA model and to indisputably identify the fibrosis pattern in the TAA model as driven from the pericentral vein region. Our data provide a valuable foundation for future work using the CDE and TAA regimens to model a variety of human chronic liver diseases.

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“…Andrographolide treatment reduces serum cholesterol, triglycerides, and low-density lipoprotein cholesterol in hyper-cholesterolemic patients and animals fed with high-fat diets 5 . Andrographolide treatment decreases hepatic neutrophil/macrophage infiltration, down regulates local inflammation, and reduces liver damage in thioacetamide-induced mouse hepatic fibrosis 6 . The anti-inflammatory effect of andrographolide is induced by inhibiting the NF-κB signaling pathway 7–9 .…”

Section: Introductionmentioning

confidence: 96%

Attenuation of Innate Immunity by Andrographolide Derivatives Through NF-κB Signaling Pathway

Nie

Chen

Wang

et al. 2017

Sci Rep

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Andrographolide derivatives or analogs exhibit potent anti-inflammatory effects in several disease models through NF-κB activity. In this study, we synthesized different andrographolide derivatives and investigated their effects on the toll-like receptor (TLR)-induced production of pro-inflammatory cytokines. Among these compounds, 3b, 5a, and 5b inhibited both TNF-α/NF-κB and TLR4/NF-κB signaling pathways. Treatment with compounds 3b, 5a, and 5b and their structural analogs, 3a and 6b, suppressed the expression of pro-inflammatory cytokines upon the activation of TLR3 and TLR4 ligands. Compounds 3b and 5a, but not 3a, 5b, or 6b, inhibited the nuclear translocation of the NF-κB p65 subunit. Treatment with compounds 3b, 5a, 3a, 5b, and 6b attenuated the phosphorylation of p65 and IκBα. Compounds 6b suppressed the expression of the NF-κB p65 subunit. However, these compounds, except for 5b, did not affect the TLR9-induced NF-κB-independent production of the pro-inflammatory cytokines, TNF-α, and IFN-β. Compound 3b potentially protected mice from LPS-induced acute pulmonary inflammation through the inhibition of p65 phosphorylation and the decrease of serum pro-inflammatory cytokines and chemokine. Our study revealed a functional structure–activity relationship between andrographolide derivatives and innate immunity. We identified compound 3b as a potent immune suppressive agent with the potential to protect acute pulmonary infection.

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Modulation of thioacetamide-induced hepatic inflammations, angiogenesis and fibrosis by andrographolide in mice

Cited by 46 publications

References 39 publications

Andrographolide inhibits hypoxia-induced HIF-1α-driven endothelin 1 secretion by activating Nrf2/HO-1 and promoting the expression of prolyl hydroxylases 2/3 in human endothelial cells

Andrographolide inhibits hypoxia-induced HIF-1α-driven endothelin 1 secretion by activating Nrf2/HO-1 and promoting the expression of prolyl hydroxylases 2/3 in human endothelial cells

Divergent Inflammatory, Fibrogenic, and Liver Progenitor Cell Dynamics in Two Common Mouse Models of Chronic Liver Injury

Attenuation of Innate Immunity by Andrographolide Derivatives Through NF-κB Signaling Pathway

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