Isorhamnetin protects against oxidative stress by activating Nrf2 and inducing the expression of its target genes

Yang, Ji Hye; Shin, Bo Yeon; Han, Jae Yun; Kim, Mi Gwang; Wi, Ji Eun; Kim, Young Woo; Cho, Il Je; Kim, Sang Chan; Shin, Sook; Ki, Sung Hwan

doi:10.1016/j.taap.2013.10.026

Cited by 112 publications

(72 citation statements)

References 46 publications

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“…In the present study, ISO dose-dependently inhibited the overgeneration of MDA and increased the T-SOD activity, which suggested antioxidative activity of ISO in diabetic rats. Similarly, certain studies have also reported its antioxidative activity in other disorders (26)(27)(28)38). Therefore, the ameliorative effects on renal damage may also benefit from the suppression of oxidative stress.…”

Section: Discussionmentioning

confidence: 91%

“…ISO is a plant flavonoid abundant in herbal medicinal plants, such as Hippophae rhamnoides L. It has been tested in inflammation-associated diseases (18,20,26) and oxidative stress-associated diseases (27,28). However, to the best of our knowledge, no studies had evaluated its effects on kidney function in DN animals, which is also associated with inflammation Table VI.…”

Section: Discussionmentioning

confidence: 99%

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Involvement of the NF-κB signaling pathway in the renoprotective effects of isorhamnetin in a type 2 diabetic rat model

et al. 2016

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Abstract. The aim of the present study was to investigate the renoprotective effects of isorhamnetin (ISO) in type 2 diabetic rats and its effects on the nuclear factor-κB (NF-κB) signaling pathway, which is associated with diabetic nephropathy. The type 2 diabetic rat model was established by a high-fat diet plus streptozocin injection and the rats were subsequently treated with two dosages of ISO, respectively. The levels of blood glucose were determined. Urinary osteopontin, kidney injury molecule-1 (KIM-1) and albumin were measured to evaluate the renal function of the rats. Renal NF-κB signaling activity was assessed by measuring the levels of NF-κB p65, phospho-NF-κB p65, inhibitor of NF-κB (IκBα) and phospho-IκBα, and the NF-κB p65 DNA-binding activity. Downstream inflammatory mediators [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, intercellular adhesion molecule-1 (ICAM-1) and transforming growth factor-β1 (TGF-β1)] of the NF-κB signaling pathway were investigated to evaluate the renal inflammatory response. Renal levels of malondialdehyde and total superoxide dismutase were detected to access the oxidative stress. Furthermore, glomerular mesangial cells (GMCs) were treated with lipopolysaccharide and ISO. In the cellular experiment, the NF-κB signaling activity, levels of TNF-α, IL-1β, IL-6, ICAM-1 and TGF-β1, and oxidative stress were also investigated. The results showed that ISO decreased the levels of urinary osteopontin, KIM-1 and albumin. ISO also inhibited the NF-κB signaling activity, decreased the production of inflammatory mediators and attenuated oxidative stress in diabetic rats and GMCs. The present investigations revealed that ISO had ameliorative effects on diabetes-induced renal damage and the activity may be associated with the negative regulation of NF-κB signaling pathway.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Involvement of the NF-κB signaling pathway in the renoprotective effects of isorhamnetin in a type 2 diabetic rat model

et al. 2016

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“…It has been reported that Iso is efficacious in protecting hepatocytes against oxidative stress by activating Nrf2 and inhibiting ROS production by up-regulating antioxidant protein HO-1 and GCL expression 19 . Iso has anti-inflammatory effects through HO-1activity, which was mediated by the Nrf2/PPAR-γ pathway [19][20][21] . Iso can also activate the NF-κB signaling pathway to inhibit inflammation and cell proliferation.…”

Section: +mentioning

confidence: 99%

Commentary: Protective Effects of Isorhamnetin on N2a Cell Against Endoplasmic Reticulum Stress-induced Injury Is Mediated by PKC?

Lu¹

2017

J Neurol Neuromedicine

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Neuronal apoptosis is an important pathophysiological factor of Alzheimer's disease (AD). Inhibition of endoplasmic reticulum stress (ERS)-induced neuronal apoptosis is an effective strategy to deal with AD. In this commentary, we summarize the relationship between AD and ERS injury-induced neuronal apoptosis, and highlight the protective effects and mechanism of isorhamnetin (Iso) against ERS-induced injury in N2a cells. Moreover, this commentary discusses the recent findings in the role of Iso in other diseases.Alzheimer's disease (AD) is a chronic neurodegenerative disease, and the fourth leading cause of death, behind heart disease, cancer and stroke 1. The clinical manifestations of AD include deteriorating cognitive function and memory, a decline in functioning in daily life activities, anda variety of neuropsychiatric symptoms and behavioral disorders 2,3 . The risk of AD gradually increases with age. There are more than 30 million AD patient living in the world today 4,5 .The etiology and pathogenesis of AD is not clear. AD is characterized by the accumulation of misfolded β-amyloid proteins caused by various genetic and environmental factors. These Aβ-plaques are associated with several pathological changes including the aggregation of misfolded proteins, formation of tissue precipitation, intracellular calcium disturbance, DNA fragmentation and lipid peroxidation. Together, these factors induce neuronal apoptosis and necrosis 6 . Thus, inhibiting neuron apoptosis is an effective way to prevent AD.The endoplasmic reticulum (ER) is theprincipal organelle for protein synthesis, protein folding and maintenance of calcium homeostasis 7 . Numerous stimuli, such as hypoxia and oxidative stress, can perturb calcium balance, and promote accumulation of unfolded and misfolded proteins in the ER lumen. This is known as endoplasmic reticulum stress (ERS) 8 . ERS is one of the key drivers of apoptosis. ERS induces apoptosis, through activation of the ASK and p38 MAPK signal pathway, trigger the kinase function of IRE1 [9][10][11] . Additionally, p38MAPK is reported to promote phosphorylation and activation of pro-apoptotic protein Bax 12,13 . Recent studies suggest that AD pathology is associated with ERS 14 . ERS generates a toxic environment in neurons, which in turn activates endoplasmic reticulum pathways that ultimately cause apoptosis 15 . Thus, inhibition of ERS injury may be an effective strategy to prevent AD.

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“…21,22) Previously, we reported that Nrf2 pathway regulates Sesn2 gene induction. 23,24) Moreover, Sesn2 small interfering RNA (siRNA) abolished the cytoprotective effect of the Nrf2 activator against H 2 O 2 . Inversely, it is also feasible that Sesn2 regulates the Nrf2 pathway.…”

Section: )mentioning

confidence: 99%

Sestrin2: A Promising Therapeutic Target for Liver Diseases

Kim

Yang

Shin

et al. 2015

Biological & Pharmaceutical Bulletin

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Sestrin2 (Sesn2), a highly conserved antioxidant protein, is induced by various stresses, including oxidative and energetic stress, and protects cells against those stresses. In normal physiological conditions, redoxhomeostasis plays an essential role in cell survival and performs the cellular functions to protect the cells against oxidative damage. The liver is susceptible to oxidative stress, since it is responsible for xenobiotic detoxification and energy metabolism. For this reason, oxidative stress is associated with the pathogenesis of liver diseases. Recently, the role of Sesn2 has been investigated in liver injury and related diseases. In this paper, we review the role of Sesn2 in the pathophysiology of liver diseases and the potential clinical applications of Sesn2 as a therapeutic target to prevent/treat liver diseases. This article promotes our understanding of liver disease progression and advances the development of strategies for pharmacological intervention.

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Isorhamnetin protects against oxidative stress by activating Nrf2 and inducing the expression of its target genes

Cited by 112 publications

References 46 publications

Involvement of the NF-κB signaling pathway in the renoprotective effects of isorhamnetin in a type 2 diabetic rat model

Involvement of the NF-κB signaling pathway in the renoprotective effects of isorhamnetin in a type 2 diabetic rat model

Commentary: Protective Effects of Isorhamnetin on N2a Cell Against Endoplasmic Reticulum Stress-induced Injury Is Mediated by PKC?

Sestrin2: A Promising Therapeutic Target for Liver Diseases

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