The role of modulation of antioxidant enzyme systems in the treatment of neurodegenerative diseases

Obuobi, Sybil; Karatayev, Sanzhar; Chai, Christina L. L.; Ee, Pui Lai Rachel; Mátyus, Péter

doi:10.1080/14756366.2016.1205047

Cited by 10 publications

(8 citation statements)

References 166 publications

(178 reference statements)

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“…lates HO-1 in different cells and tissues [34]. As shown in Figure 3E, the ex trol cells to the extract did not affect the constitutive levels of the Keap-1 p marked Keap-1 reduction observed in LPS-treated cells was not amended b of NaE.…”

Section: Effects Of Nae On the Inflammatory Response Induced By Lps O...mentioning

confidence: 77%

“…We also examined, both in resting and reactive microglial cells, the expression levels of Keap-1, a crucial inhibitor protein of the transcription factor Nrf2, which also upregulates HO-1 in different cells and tissues [34]. As shown in Figure 3E, the exposure of control cells to the extract did not affect the constitutive levels of the Keap-1 protein, and the marked Keap-1 reduction observed in LPS-treated cells was not amended by the presence of NaE.…”

Section: Effects Of Nae On the Inflammatory Response Induced By Lps O...mentioning

confidence: 99%

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Anti-Neuroinflammatory Potential of a Nectandra angustifolia (Laurel Amarillo) Ethanolic Extract

et al. 2023

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Microglia, the resident macrophage-like population in the CNS, plays an important role in the pathogenesis of many neurodegenerative disorders. Nectandra genus is known to produce different metabolites with anti-inflammatory, anti-oxidant and analgesic properties. Although the species Nectandra angustifolia is popularly used for the treatment of different types of inflammatory processes, its biological effects on neuroinflammation have not yet been addressed. In this study, we have investigated the role of a Nectandra angustifolia ethanolic extract (NaE) in lipopolysaccharide (LPS)-induced neuroinflammation in vitro and in vivo. In LPS-activated BV2 microglial cells, NaE significantly reduced the induced proinflammatory mediators TNF-α, IL-1β, IL-6, COX-2 and iNOS, as well as NO accumulation, while it promoted IL-10 secretion and YM-1 expression. Likewise, reduced CD14 expression levels were detected in microglial cells in the NaE+LPS group. NaE also attenuated LPS-induced ROS and lipid peroxidation build-up in BV2 cells. Mechanistically, NaE prevented NF-κB and MAPKs phosphorylation, as well as NLRP3 upregulation when added before LPS stimulation, although it did not affect the level of some proteins related to antioxidant defense such as Keap-1 and HO-1. Additionally, we observed that NaE modulated some activated microglia functions, decreasing cell migration, without affecting their phagocytic capabilities. In LPS-injected mice, NaE pre-treatment markedly suppressed the up-regulated TNF-α, IL-6 and IL-1β mRNA expression induced by LPS in brain. Our findings indicate that NaE is beneficial in preventing the neuroinflammatory response both in vivo and in vitro. NaE may regulate microglia homeostasis, not only restraining activation of LPS towards the M1 phenotype but promoting an M2 phenotype.

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Section: Effects Of Nae On the Inflammatory Response Induced By Lps O...mentioning

confidence: 77%

Section: Effects Of Nae On the Inflammatory Response Induced By Lps O...mentioning

confidence: 99%

Anti-Neuroinflammatory Potential of a Nectandra angustifolia (Laurel Amarillo) Ethanolic Extract

et al. 2023

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“…Therefore, Nrf2 activators that produce antioxidants capable of scavenging ROS would be applied for diseases such as high glucose induced-diabetes and diabetic nephropathy. Many studies have focused on developing Nrf2 modulators, as Nrf2 activators could be preventive and therapeutic agents for neurodegenerative diseases [Obuobi et al, 2016], retinal diseases [Nakagami, 2016], chronic kidney diseases [Saito, 2013], including oxidative stress-induced diseases. HX-1171 is a novel compound that was reported to inhibit the production of nitric oxide and activate the transcription factor nuclear factor kappa B [Liu et al, 2002].…”

Section: Discussionmentioning

confidence: 99%

HX‐1171, a Novel Nrf2 Activator, Induces NQO1 and HMOX1 Expression

Kim

Shin

et al. 2017

J of Cellular Biochemistry

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HX-1171 (1-O-hexyl-2,3,5-trimethylhydroquinone) is a novel synthesized vitamin E derivative, which reportedly has positive effects on various diseases and conditions, such as liver fibrosis, hepatic cirrhosis, and cancer. In this study, we analyzed the transcriptional activity induced by HX-1171. Results from reverse transcription polymerase chain reaction and promoter assays reveal that HX-1171 increased the expression of NQO1 and HMOX1, encoding antioxidant-related enzymes, in A549 human lung epithelial cells. The activity of nuclear factor-E2-related factor (Nrf2), a key transcriptional factor for antioxidative enzymes, was examined in HX-1171-treated cells. Confocal microscopy and Western blotting showed that HX-1171 effectively induced the nuclear translocation and transcriptional activity of Nrf2. We conclude that HX-1171, a novel Nrf2 activator, may be a promising therapeutic agent for oxidative stress-induced diseases. J. Cell. Biochem. 118: 3372-3380, 2017. © 2017 Wiley Periodicals, Inc.

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“…Therefore, the Nrf2 pathway has been extensively studied and its role in neurodegenerative diseases has been confirmed. The protective effect of Nrf2 activation has led to the development of a FDA approved drug, Tecfidera (dimethyl fumarate), Biogen Idec (Cambridge, MA, USA), for the treatment of patients with relapsing multiple sclerosis and the application of Nrf2 activators for other diseases is currently being researched [28,29,30]. The development of new antioxidant molecules that have effects on mitochondria and on the antioxidant enzymes can contribute to the expansion of our knowledge about the potential of antioxidant therapies in neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Antioxidant Activity of the Marine Pyrroloiminoquinone Makaluvamines

et al. 2016

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Makaluvamines are pyrroloiminoquinones isolated from Zyzzya sponges. Until now, they have been described as topoisomerase II inhibitors with cytotoxic effects in diverse tumor cell lines. In the present work, seven makaluvamines were tested in several antioxidant assays in primary cortical neurons and neuroblastoma cells. Among the alkaloids studied, makaluvamine J was the most active in all the assays. This compound was able to reduce the mitochondrial damage elicited by the well-known stressor H2O2. The antioxidant properties of makaluvamine J are related to an improvement of the endogenous antioxidant defenses of glutathione and catalase. SHSY5Y assays proved that this compound acts as a Nrf2 activator leading to an improvement of antioxidant defenses. A low concentration of 10 nM is able to reduce the reactive oxygen species release and maintain a correct mitochondrial function. Based on these results, non-substituted nitrogen in the pyrrole plus the presence of a p-hydroxystyryl without a double bond seems to be the most active structure with a complete antioxidant effect in neuronal cells.

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The role of modulation of antioxidant enzyme systems in the treatment of neurodegenerative diseases

Cited by 10 publications

References 166 publications

Anti-Neuroinflammatory Potential of a Nectandra angustifolia (Laurel Amarillo) Ethanolic Extract

Anti-Neuroinflammatory Potential of a Nectandra angustifolia (Laurel Amarillo) Ethanolic Extract

HX‐1171, a Novel Nrf2 Activator, Induces NQO1 and HMOX1 Expression

Evaluation of the Antioxidant Activity of the Marine Pyrroloiminoquinone Makaluvamines

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