Glycyrrhizin ameliorates high fat diet-induced obesity in rats by activating NrF2 pathway

El-Magd, Nada F. Abo; El-Mesery, Mohamed; El-Karef, Amro; El‐Shishtawy, Mamdouh M.

doi:10.1016/j.lfs.2017.11.005

Cited by 46 publications

(33 citation statements)

References 44 publications

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“…Among them, glycyrrhizin, a glycoconjugated triterpene, was the first identified to have antiviral activity and has been used to treat patients with chronic hepatitis B and C due to its potent anti-inflammatory activity (Mbeunkui and Johann, 2009). Glycyrrhizin attenuated high-fat diet-induced obesity in Wistar rats by increasing insulin receptor expression and activating NrF2 and the homooxygenase-1 pathway (Abo El-Magd et al, 2018). In addition, glycyrrhizin has been reported to induce apoptosis in various cancers, including breast, liver, lung, and pancreatic cancers, by the generation of reactive oxygen species, cell cycle arrest, and/or autophagy (Huang et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Isoliquiritin Apioside Suppresses in vitro Invasiveness and Angiogenesis of Cancer Cells and Endothelial Cells

Kim

Yeul

2018

Front. Pharmacol.

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Several components isolated from Glycyrrhizae radix rhizome (GR), including glycyrrhizin, liquiritin, and liquiritigenin, have been shown to induce cancer cell death and inhibit cancer metastasis. Isoliquiritin apioside (ISLA), a component isolated from GR, has been effective for treating tetanic contraction and genotoxicity. However, the effects of ISLA on the metastasis and angiogenesis of malignant cancer cells and endothelial cells (ECs) have not been reported. In this study, we found that up to 100 μM ISLA did not affect cell proliferation but efficiently suppressed the metastatic ability of HT1080 cells, as assessed by scratch-wound migration, Transwell® migration, scratch-wound invasion, Transwell® invasion, and three-dimensional spheroid invasion. ISLA significantly decreased phorbol 12-myristate 13-acetate (PMA)-induced increases in matrix metalloproteinase (MMP) activities and suppressed PMA-induced activation of mitogen-activated protein kinase as well as NF-κB, which are involved in cancer metastasis. In addition, ILSA treatment reduced the production of pro-angiogenic factors in HT1080 cells, including MMP-9, placental growth factor, and vascular endothelial growth factor under normoxia as well as hypoxia conditions, by impairing the hypoxia-inducible factor-1α pathway. We also found that the abilities of human umbilical vein ECs to migrate across the Transwell® and to form tube-like structures were significantly reduced by ISLA treatment. Moreover, using the chorioallantoic membrane assay, vessel formation with or without vascular endothelial growth factor was significantly suppressed by ISLA. These results suggested that ISLA possesses anti-metastatic and anti-angiogenic abilities in malignant cancer cells and ECs, with no cytotoxicity. ISLA may therefore be a safe and effective lead compound to develop anti-cancer drug for limiting the spread of primary tumors to distant organs to form secondary tumors.

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Section: Discussionmentioning

confidence: 99%

Isoliquiritin Apioside Suppresses in vitro Invasiveness and Angiogenesis of Cancer Cells and Endothelial Cells

Kim

Yeul

2018

Front. Pharmacol.

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“…A study conducted in 2003 after the SARS outbreak [ 90 ] found that glycyrrhizin, a triterpenoid from liquorice roots, inhibited the replication of SARS-CoV in two clinical isolates of coronaviruses from patients with SARS. The potential effect of glycyrrhizin on NRF2 was not studied; however, glycyrrhizin has been shown to activate NRF2 in other settings [ 77 , 91 ], and it is plausible that at least part of the observed antiviral effect was due to NRF2 activation.…”

Section: Armamentarium Of Available Nrf2 Activators For Potential Antmentioning

confidence: 99%

Can Activation of NRF2 Be a Strategy against COVID-19?

Cuadrado

Pajares

Benito

et al. 2020

Trends in Pharmacological Sciences

180

183

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Acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 is largely the result of a dysregulated host response, followed by damage to alveolar cells and lung fibrosis. Exacerbated proinflammatory cytokines release (cytokine storm) and loss of T lymphocytes (leukopenia) characterize the most aggressive presentation. We propose that a multifaceted anti-inflammatory strategy based on pharmacological activation of nuclear factor erythroid 2 p45-related factor 2 (NRF2) can be deployed against the virus. The strategy provides robust cytoprotection by restoring redox and protein homeostasis, promoting resolution of inflammation, and facilitating repair. NRF2 activators such as sulforaphane and bardoxolone methyl are already in clinical trials. The safety and efficacy information of these modulators in humans, together with their well-documented cytoprotective and anti-inflammatory effects in preclinical models, highlight the potential of this armamentarium for deployment to the battlefield against COVID-19.

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“…Before testing the antioxidant potential of SDT, we conducted a UPLC analysis to assess the quality of SDT and observed chemical markers representing nine medicinal herbs effectively solubilized in the SDT water extract. Of the nine marker compounds, glycyrrhizic acid, ferulic acid, cinnamic acid, 6-gingerol, 5-hydroxymethyl-2-furfural, paeoniflorin, and ginsenoside Rg1 have been reported to reduce oxidative stress in experimental hepatic disorders [ 25 – 31 ]. However, the concentrations of the nine marker compounds were too low to explain the potent hepatoprotective effects of SDT.…”

Section: Discussionmentioning

confidence: 99%

Sipjeondaebo-tang Alleviates Oxidative Stress‐Mediated Liver Injury through Activation of the CaMKK2‐AMPK Signaling Pathway

Park

Kim

Jung

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Sipjeondaebo-tang (SDT) is used frequently as a herbal prescription to treat deficiency syndromes in traditional Korean medicine. We investigated the hepatoprotective effects of SDT against oxidative stress and attempted to clarify the underlying molecular mechanisms. SDT pretreatment reduced arachidonic acid (AA) plus iron-mediated cytotoxicity in a concentration-dependent manner and prevented changes in apoptosis-related protein expression. In addition, SDT pretreatment significantly reduced glutathione depletion, hydrogen peroxide production, and mitochondrial dysfunction via treatment with AA plus iron. SDT increased the phosphorylation of AMP-activated protein kinase (AMPK) in accordance with the phosphorylation of Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2). Experiments using an AMPK chemical inhibitor (Compound C) or CaMKK2 chemical inhibitor (STO-609) suggested that the CaMKK2-AMPK signaling pathway contributes to SDT-mediated protection of mitochondria and cells. Moreover, administration of SDT for 4 consecutive days to mice significantly reduced the alanine aminotransferase and aspartate aminotransferase activities induced by carbon tetrachloride, and the numbers of degenerated hepatocytes, infiltrated inflammatory cells, nitrotyrosine-positive cells, and 4-hydroxynonenal-positive cells in liver tissue. Therefore, SDT protects hepatocytes from oxidative stress via CaMKK2-dependent AMPK activation and has the therapeutic potential to prevent or treat oxidative stress-related liver injury.

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Glycyrrhizin ameliorates high fat diet-induced obesity in rats by activating NrF2 pathway

Cited by 46 publications

References 44 publications

Isoliquiritin Apioside Suppresses in vitro Invasiveness and Angiogenesis of Cancer Cells and Endothelial Cells

Isoliquiritin Apioside Suppresses in vitro Invasiveness and Angiogenesis of Cancer Cells and Endothelial Cells

Can Activation of NRF2 Be a Strategy against COVID-19?

Sipjeondaebo-tang Alleviates Oxidative Stress‐Mediated Liver Injury through Activation of the CaMKK2‐AMPK Signaling Pathway

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