Orientin-mediated Nrf2/HO-1 signal alleviates H2O2-induced oxidative damage via induction of JNK and PI3K/AKT activation

Xiao, Qingfei; Piao, Rongli; Wang, Hongyue; Li, Chenhao; Song, Liangsong

doi:10.1016/j.ijbiomac.2018.06.130

Cited by 64 publications

(43 citation statements)

References 30 publications

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“…In recent years, researchers have paid particular attention to the PI3K/Akt/Nrf2/HO-1 pathway that plays a pivotal role in the resistance to oxidative stress [ 43 , 44 , 45 ]. Nrf2 is a transcription factor that can regulate endogenous antioxidant defense and also a molecular target for pharmacological resistance to oxidative damage [ 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Panax notoginseng Saponins Protect Cerebral Microvascular Endothelial Cells against Oxygen-Glucose Deprivation/Reperfusion-Induced Barrier Dysfunction via Activation of PI3K/Akt/Nrf2 Antioxidant Signaling Pathway

Zhao

et al. 2018

Molecules

116

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Oxidative stress plays a critical role in cerebral ischemia/reperfusion (I/R)-induced blood-brain barrier (BBB) disruption. Panax notoginseng saponins (PNS) possess efficient antioxidant activity and have been used in the treatment of cerebral ischemic stroke in China. In this study, we determined the protective effects of PNS on BBB integrity and investigated the underlying mechanism in cerebral microvascular endothelial cells (bEnd.3) exposed to oxygen-glucose deprivation/reperfusion (OGD/R). MTT and LDH release assays revealed that PNS mitigated the OGD/R-induced cell injury in a dose-dependent manner. TEER and paracellular permeability assays demonstrated that PNS alleviated the OGD/R-caused disruption of BBB integrity. Fluorescence probe DCFH-DA showed that PNS suppressed ROS generation in OGD/R-treated cells. Immunofluorescence and western blot analysis indicated that PNS inhibited the degradation of tight junction proteins triggered by OGD/R. Moreover, mechanism investigations suggested that PNS increased the phosphorylation of Akt, the activity of nuclear Nrf2, and the expression of downstream antioxidant enzyme HO-1. All the effects of PNS could be reversed by co-treatment with PI3K inhibitor LY294002. Taken together, these observations suggest that PNS may act as an extrinsic regulator that activates Nrf2 antioxidant signaling depending on PI3K/Akt pathway and protects against OGD/R-induced BBB disruption in vitro.

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Section: Discussionmentioning

confidence: 99%

Panax notoginseng Saponins Protect Cerebral Microvascular Endothelial Cells against Oxygen-Glucose Deprivation/Reperfusion-Induced Barrier Dysfunction via Activation of PI3K/Akt/Nrf2 Antioxidant Signaling Pathway

Zhao

et al. 2018

Molecules

116

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“…The liver regulates oxidative stress mainly by activating some antioxidant enzymes, such as CAT, SOD, and GSH‐Px (Wu et al, ; Xiao, Piao, Wang, Li, & Song, ), which is related to the production and elimination of ROS. In this study, phlorizin reversed the decrease in the activity of CAT, SOD, and GSH‐Px induced by H 2 O 2 in HepG2 cells, while no effect was detected in normal HepG2 cells by treated with phlorizin as compared to the control group (Figure ).…”

Section: Discussionmentioning

confidence: 99%

Protective effect of apple phlorizin on hydrogen peroxide‐induced cell damage in HepG2 cells

et al. 2019

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Apple phlorizin has many biological activities, such as antioxidant and liver protection. The present study aimed to evaluate the roles of apple phlorizin against hydrogen peroxide (H2O2)‐induced oxidative damage in HepG2 cells. In this study, treatment with apple phlorizin (100 and 150 μg/ml) decreased the production of reactive oxygen species and alleviated apoptosis as well as DNA damage in H2O2‐induced HepG2 cells. These effects were associated with the increased activity of antioxidant enzymes, enhanced the ARE‐driven phase II antioxidant gene expression and its upstream Nrf2 protein expression, and decreased apoptosis‐related gene expression. However, the phase II antioxidant gene expression and Nrf2 protein expression upregulated by phlorizin were reversed by Nrf2 shRNA transfection. These results showed that phlorizin relieves oxidative stress, DNA damage, and apoptosis in H2O2‐induced HepG2 cells, at least partially, by regulating the expression of Nrf2 protein and apoptosis‐related genes. Practical applications Apple phlorizin is a polyphenol compound extracted from apple or apple juice. This report highlighted a protective effect of phlorizin on antioxidant stress, DNA damage, and apoptosis in H2O2‐induced HepG2 cells. These results suggested that phlorizin may be developed for functional foods.

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“…Several are the stimuli and signaling pathways leading Nrf2 to induce HMOX1 expression. For instance, exposure to the flavonoid Orientin (Ori) can alleviate hydrogen peroxide-induced oxidative impairment in RAW264.7 cells, by induction of Nrf2/HMOX1 axis, through c-Jun N-terminal kinases (JNK) and phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT) activation ( 17 ). Cytokines are another stimuli for HMOX1 expression ( 18 ) and it has been demonstrated that in human macrophages, IL-10 and IL-6-induced expression of HMOX1 required the activation of the signal transducer and activator of transcription 3 (STAT3) ( 19 ).…”

Section: Role Of Hmox1 Under Physiological Conditionsmentioning

confidence: 99%

Heme Oxygenase-1 as a Modulator of Intestinal Inflammation Development and Progression

et al. 2018

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Heme Oxygenase 1 (HMOX1) is an enzyme that catalyzes the reaction that degrades the heme group contained in several important proteins, such as hemoglobin, myoglobin, and cytochrome p450. The enzymatic reaction catalyzed by HMOX1 generates Fe2+, biliverdin and CO. It has been shown that HMOX1 activity and the by-product CO can downmodulate the damaging immune response in several models of intestinal inflammation as a result of pharmacological induction of HMOX1 expression and the administration of non-toxic amounts of CO. Inflammatory Bowel Diseases, which includes Crohn's Disease (CD) and Ulcerative Colitis (UC), are one of the most studied ailments associated to HMOX1 effects. However, microbiota imbalances and infections are also important factors influencing the occurrence of acute and chronic intestinal inflammation, where HMOX1 activity may play a major role. As part of this article we discuss the immune modulatory capacity of HMOX1 during IBD, as well during the infections and interactions with the microbiota that contribute to this inflammatory disease.

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Orientin-mediated Nrf2/HO-1 signal alleviates H2O2-induced oxidative damage via induction of JNK and PI3K/AKT activation

Cited by 64 publications

References 30 publications

Panax notoginseng Saponins Protect Cerebral Microvascular Endothelial Cells against Oxygen-Glucose Deprivation/Reperfusion-Induced Barrier Dysfunction via Activation of PI3K/Akt/Nrf2 Antioxidant Signaling Pathway

Panax notoginseng Saponins Protect Cerebral Microvascular Endothelial Cells against Oxygen-Glucose Deprivation/Reperfusion-Induced Barrier Dysfunction via Activation of PI3K/Akt/Nrf2 Antioxidant Signaling Pathway

Protective effect of apple phlorizin on hydrogen peroxide‐induced cell damage in HepG2 cells

Heme Oxygenase-1 as a Modulator of Intestinal Inflammation Development and Progression

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