Keap1/Nrf2/HO-1 signaling pathway contributes to p-chlorodiphenyl diselenide antidepressant-like action in diabetic mice

Zborowski, Vanessa Angonesi; Heck, Suélen Osório; Vencato, Marina S.; Pinton, Simone; Marques, Luiza Souza; Nogueira, Cristina Wayne

doi:10.1007/s00213-019-05372-3

Cited by 19 publications

(7 citation statements)

References 53 publications

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“…Physiologically, Nrf2 is inactivated by Keap1 binding. Under oxidative stress, excess ROS prompts Nrf2 dissociation, activation, nuclear translocation, and binding to the ARE, which promotes the activation of downstream antioxidant enzymes (e.g., HO-1) for transcription and antioxidant effects [ 99 ]. The upstream PI3K/Akt pathway or MAPK signalling pathway can activate Nrf2/ARE signaling pathway and upregulate the expression of antioxidant enzymes [ 62 , 100 ].…”

Section: Discussionmentioning

confidence: 99%

Research hotspots and frontiers of preconditioning in cerebral ischemia: A bibliometric analysis

Zhang,

Zhou,

Zhao

et al. 2024

Heliyon

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Section: Discussionmentioning

confidence: 99%

Research hotspots and frontiers of preconditioning in cerebral ischemia: A bibliometric analysis

Zhang,

Zhou,

Zhao

et al. 2024

Heliyon

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“…DM is associated with neuroinflammation, which may lead to damages or even death of brain neurons. Jawale et al reported that DM increased the levels of TNF-α in the brain, which mediated anxiety and depressive-like behavior [ 40 , 41 ]. Inflammatory process in DM is a by-product of excessive generation of reactive species and increased oxidative stress, leading to the trigger of NF-κB signaling and subsequent increase in proinflammatory genes [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

LC/ESI/TOF-MS Characterization, Anxiolytic and Antidepressant-like Effects of Mitragyna speciosa Korth Extract in Diabetic Rats

2022

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In this study, the attenuative effects of the hydro-alcoholic extract from Mitragyna speciosa (MSE) against diabetes-induced anxiety and depression-like behaviors were examined. In addition, UPLC/ESI/TOF-MS analysis was performed to identify the phytochemical nature of MSE. DM was induced using a combination of high fructose/streptozotocin, and the diabetic rats were treated with MSE (50 and 200 mg/kg) for 5 weeks. After treatment, the animals were subjected to a forced swim test, open field test and elevated plus-maze tests. Additionally, proinflammatory cytokines and oxidative stress parameters were evaluated in the brain tissues of the rats. UPLC/ESI/TOF-MS analysis revealed that MSE is abundantly rich in polyphenolic constituents, notably flavonoid and phenolic glycosides. Behavioral tests and biochemical analyses indicated that diabetic rats showed significantly increased anxiety and depressive-like behavioral deficits, brain oxidative stress and pro-inflammatory cytokines levels (IL-1β, IL-6 and TNF-α). Treatment with MSE (50 and 200 mg/kg) significantly attenuated increased blood glucose level, depressive and anxiety-like behaviors in diabetic rats. Additionally, the antioxidant enzymes activities were markedly increased in MSE-treated animals, while TNF-α, IL-1β and IL-6 cytokines were notably suppressed. Taken together, these results suggested that MSE has potentials as antidepressant and anxiolytic-like effects and improves the brain oxido-inflammatory status in diabetic rats.

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“…Under physiological condition, Nrf2 and Keap1 exist in the cytoplasm, and the inactive Nrf2 is ubiquitinated and then degraded. When oxidative stress occurs in the body, Nrf2 and Keap1 are dissociated and activated, transferred to the nucleus, and combined with the corresponding sites of the ARE in the nucleus, thereby activating the transcription of antioxidant enzymes and detoxification enzymes downstream of the pathway ( Figure 2 ), and working with related factors to improve the antioxidant capacity of cells [ 95 ]. Keap1 contains an NES in the IVR domain.…”

Section: Activation Of Nrf2 Signaling Pathway In Cerebral Ischemic St...mentioning

confidence: 99%

Nrf2 Regulates Oxidative Stress and Its Role in Cerebral Ischemic Stroke

et al. 2022

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Cerebral ischemic stroke is characterized by acute ischemia in a certain part of the brain, which leads to brain cells necrosis, apoptosis, ferroptosis, pyroptosis, etc. At present, there are limited effective clinical treatments for cerebral ischemic stroke, and the recovery of cerebral blood circulation will lead to cerebral ischemia-reperfusion injury (CIRI). Cerebral ischemic stroke involves many pathological processes such as oxidative stress, inflammation, and mitochondrial dysfunction. Nuclear factor erythroid 2-related factor 2 (Nrf2), as one of the most critical antioxidant transcription factors in cells, can coordinate various cytoprotective factors to inhibit oxidative stress. Targeting Nrf2 is considered as a potential strategy to prevent and treat cerebral ischemia injury. During cerebral ischemia, Nrf2 participates in signaling pathways such as Keap1, PI3K/AKT, MAPK, NF-κB, and HO-1, and then alleviates cerebral ischemia injury or CIRI by inhibiting oxidative stress, anti-inflammation, maintaining mitochondrial homeostasis, protecting the blood–brain barrier, and inhibiting ferroptosis. In this review, we have discussed the structure of Nrf2, the mechanisms of Nrf2 in cerebral ischemic stroke, the related research on the treatment of cerebral ischemia through the Nrf2 signaling pathway in recent years, and expounded the important role and future potential of the Nrf2 pathway in cerebral ischemic stroke.

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Keap1/Nrf2/HO-1 signaling pathway contributes to p-chlorodiphenyl diselenide antidepressant-like action in diabetic mice

Cited by 19 publications

References 53 publications

Research hotspots and frontiers of preconditioning in cerebral ischemia: A bibliometric analysis

Research hotspots and frontiers of preconditioning in cerebral ischemia: A bibliometric analysis

LC/ESI/TOF-MS Characterization, Anxiolytic and Antidepressant-like Effects of Mitragyna speciosa Korth Extract in Diabetic Rats

Nrf2 Regulates Oxidative Stress and Its Role in Cerebral Ischemic Stroke

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