Phytochemical Activation of Nrf2 Protects Human Coronary Artery Endothelial Cells against an Oxidative Challenge

Donovan, Elise L.; McCord, Joe M.; Reuland, Danielle J.; Miller, Benjamin F.; Hamilton, Karyn L.

doi:10.1155/2012/132931

Cited by 60 publications

(45 citation statements)

References 39 publications

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“…Furthermore, among the antioxidant and detoxification enzymes, Heme oxygenase-1 (HO-1) and glutamate-Lcysteine ligase catalytic subunit (GCLC) are the most important. Recent studies have shown that activation of Nrf2 plays an important role in acute liver injury both in vitro and in vivo (7,8). To date, multiple signaling kinases have been reported to regulate Nrf2, including mitogen-activated protein kinase (MAPK), protein kinase C (PKC) and phosphatidylinositol-3-kinase (PI3K) (9,10).…”

Section: Introductionmentioning

confidence: 99%

Salvianolic acid B protects against acetaminophen hepatotoxicity by inducing Nrf2 and phase II detoxification gene expression via activation of the PI3K and PKC signaling pathways

Lin

Zhai

Wang

et al. 2015

Journal of Pharmacological Sciences

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Acetaminophen (APAP) is used drugs worldwide for treating pain and fever. However, APAP overdose is the principal cause of acute liver failure in Western countries. Salvianolic acid B (SalB), a major water-soluble compound extracted from Radix Salvia miltiorrhiza, has well-known antioxidant and anti-inflammatory actions. We aimed to evaluate the ability of SalB to protect against APAP-induced acute hepatotoxicity by inducing nuclear factor-erythroid-2-related factor 2 (Nrf2) expression. SalB pretreatment ameliorated acute liver injury caused by APAP, as indicated by blood aspartate transaminase levels and histological findings. Moreover, SalB pretreatment increased the expression of Nrf2, Heme oxygenase-1 (HO-1) and glutamate-l-cysteine ligase catalytic subunit (GCLC). Furthermore, the HO-1 inhibitor zinc protoporphyrin and the GCLC inhibitor buthionine sulfoximine reversed the protective effect of SalB. Additionally, siRNA-mediated depletion of Nrf2 reduced the induction of HO-1 and GCLC by SalB, and SalB pretreatment activated the phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC) signaling pathways. Both inhibitors (PI3K and PKC) blocked the protective effect of SalB against APAP-induced cell death, abolishing the SalB-induced Nrf2 activation and decreasing HO-1 and GCLC expression. These results indicated that SalB induces Nrf2, HO-1 and GCLC expression via activation of the PI3K and PKC pathways, thereby protecting against APAP-induced liver injury.

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Section: Introductionmentioning

confidence: 99%

Salvianolic acid B protects against acetaminophen hepatotoxicity by inducing Nrf2 and phase II detoxification gene expression via activation of the PI3K and PKC signaling pathways

Lin

Zhai

Wang

et al. 2015

Journal of Pharmacological Sciences

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“…Moreover, these phytochemicals are most appropriate in protecting oxidative stress-related damages due to their tendency to exert better protective effect without any distinct side effect (Donovan et al, 2012). As a naturally occurring plant phenol, 6-gingerol has antioxidant activity.…”

Section: Introductionmentioning

confidence: 99%

“…The most common outcome of oxidative stress is the increased damage of lipid, DNA and proteins that resulted in the development of different pathologies (Donovan et al, 2012). The aim of this study was to investigate the possibility that 6-gingerol may inhibit the oxidative DNA damage of hydrogen peroxide in human umbilical vein endothelia cells (HUVECs).…”

Section: Introductionmentioning

confidence: 99%

6-Gingerol Attenuates Hydrogen Peroxide-induced DNA Damage in Human Umbilical Vein Endothelia Cells

Wang

Yang

Jiang

et al. 2014

FSTR

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An imbalance of oxidation and antioxidation is one of the primary causes of atherosclerosis. The use of naturalplant compounds with effects has been proven to have clinical relevance. 6-Gingerol, one of the major components of ginger, has diverse pharmacologic effects. In this study, the chemoprotective effect of 6-gingerol against hydrogen peroxide-induced DNA damage in human umbilical vein endothelia cells (HUVECs) was investigated. The comet assay was used to monitor DNA strand breaks. To further elucidate the underlying mechanisms, we tested lysosomal membrane stability, mitochondrial membrane potential, the intracellular generation of reactive oxygen species (ROS) and reduced glutathione (GSH). Our data revealed that 6-gingerol significantly reduced the DNA strand breaks caused by hydrogen peroxide. 6-Gingerol effectively suppressed hydrogen peroxide-induced intracellular ROS formation. The GSH depletion in HUVECs was also attenuated by 6-gingerol pretreatment. Moreover, lysosomal membrane stability was destroyed and mitochondrial membrane potential decreased after treated by hydrogen peroxide. Those effects can be protected by 6-gingerol. These firmly indicate 6-gingerol has a strong protective ability against the DNA damage caused by hydrogen peroxide in HUVECs, and the mechanism may relate to the antioxidant activity. Our data suggest 6-gingerol may be beneficial in the prevention of atherosclerosis.

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“…Nrf2 promotes cell survival by binding the antioxidant response element (ARE) in the promoter of downstream target genes that promote detoxification of xenobiotics and scavenging of reactive oxygen species (ROS). The benefit of Nrf2 activation has been demonstrated in various pathological states such as diabetes, chemoprevention, and cardiovascular and neurological diseases [1–5]. …”

Section: Introductionmentioning

confidence: 99%

Nrf2 Is Crucial to Graft Survival in a Rodent Model of Heart Transplantation

Qiu

Whitman

et al. 2013

Oxidative Medicine and Cellular Longevity

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Currently, the sole treatment option for patients with heart failure is transplantation. The battle of prolonging graft survival and modulating innate and adaptive immune responses is still being waged in the clinic and in research labs. The transcription factor Nrf2 controls major cell survival pathways and is central to moderating inflammation and immune responses. In this study the effect of Nrf2 levels in host recipient C57BL/6 mice on Balb/c allogeneic graft survival was examined. Importantly, Nrf2−/− recipient mice could not support the graft for longer than 7.5 days on average, whereas activation of Nrf2 by sulforaphane in Nrf2+/+ hosts prolonged graft survival to 13 days. Several immune cells in the spleen of recipient mice were unchanged; however, CD11b+ macrophages were significantly increased in Nrf2−/− mice. In addition, IL-17 mRNA levels were elevated in grafts transplanted into Nrf2−/− mice. Although Nrf2 appears to play a crucial role in graft survival, the exact mechanism is yet to be fully understood.

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Phytochemical Activation of Nrf2 Protects Human Coronary Artery Endothelial Cells against an Oxidative Challenge

Cited by 60 publications

References 39 publications

Salvianolic acid B protects against acetaminophen hepatotoxicity by inducing Nrf2 and phase II detoxification gene expression via activation of the PI3K and PKC signaling pathways

Salvianolic acid B protects against acetaminophen hepatotoxicity by inducing Nrf2 and phase II detoxification gene expression via activation of the PI3K and PKC signaling pathways

6-Gingerol Attenuates Hydrogen Peroxide-induced DNA Damage in Human Umbilical Vein Endothelia Cells

Nrf2 Is Crucial to Graft Survival in a Rodent Model of Heart Transplantation

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