Mitochondrial Target of Nobiletin's Action

Sharikadze, Nino; Jojua, Natia; Sepashvili, Maia; Zhuravliova, Elene; Mikeladze, David

doi:10.1177/1934578x1601101215

Cited by 6 publications

(5 citation statements)

References 49 publications

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“…Several studies have demonstrated that NOB plays an important role in modulating mitochondrial function, including influencing the mitochondrial membrane potential [ 20 , 21 , 22 , 23 ]. To explore whether NOB can improve the mitochondrial function in activated astrocytes induced by hypoxia, we detected the mitochondrial membrane potential using a JC-1 Assay Kit.…”

Section: Resultsmentioning

confidence: 99%

Nobiletin Alleviates Astrocyte Activation and Oxidative Stress Induced by Hypoxia In Vitro

Wang

Gao

et al. 2022

Molecules

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Increasing evidence indicates that nobiletin (NOB) is a promising neuroprotective agent. Astrocyte activation plays a key role in neurodegenerative disorders. Thus, this study aims to investigate the effects of NOB on astrocyte activation and the potential mechanisms. In this study, astrocytes were exposed to hypoxia injury for 24 h to induce activation in vitro. Glial fibrillary acidic protein (GFAP) was chosen as a marker of astrocyte activation. To evaluate the effects of NOB on the migration of activated astrocytes, we used a scratch wound healing assay and Transwell migration assay. In addition, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), mitochondrial membrane potential, Nrf2 and HO-1 were measured to investigate the mechanisms of NOB in the activation of astrocytes. We found that NOB alleviated astrocyte activation and decreased GFAP expression during hypoxia. Simultaneously, NOB alleviated the migration of astrocytes induced by hypoxia. With NOB treatment, hypoxia-induced oxidative stress was partially reversed, including reducing the production of ROS and MDA. Furthermore, NOB significantly improved the mitochondrial dysfunction in activated astrocytes. Finally, NOB promoted Nrf2 nuclear translocation and HO-1 expression in response to continuous oxidative damage. Our study indicates, for the first time, that NOB alleviates the activation of astrocytes induced by hypoxia in vitro, in part by ameliorating oxidative stress and mitochondrial dysfunction. This provides new insights into the neuroprotective effects of NOB.

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Section: Resultsmentioning

confidence: 99%

Nobiletin Alleviates Astrocyte Activation and Oxidative Stress Induced by Hypoxia In Vitro

Wang

Gao

et al. 2022

Molecules

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“…Li and coauthors demonstrated that caffeic acid inhibits both JAK/STAT and ERK1/2 pathways, as well as cell proliferation [ 71 ]. Moreover, it was shown that nobiletin, a methylated flavonoid found in citrus peels, suppresses the proliferation of C6 rat glioma cells by inhibiting RAS activity and subsequently reducing MEK/ERK signalling [ 72 ]. The ERK1/2 expression levels did not change significantly following any treatment, while the p-ERK2/ERK2 ratio decreased after pre-treatment with coffee phenolic metabolites.…”

Section: Discussionmentioning

confidence: 99%

Study of the Antioxidant Effects of Coffee Phenolic Metabolites on C6 Glioma Cells Exposed to Diesel Exhaust Particles

et al. 2021

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The contributing role of environmental factors to the development of neurodegenerative diseases has become increasingly evident. Here, we report that exposure of C6 glioma cells to diesel exhaust particles (DEPs), a major constituent of urban air pollution, causes intracellular reactive oxygen species (ROS) production. In this scenario, we suggest employing the possible protective role that coffee phenolic metabolites may have. Coffee is a commonly consumed hot beverage and a major contributor to the dietary intake of (poly) phenols. Taking into account physiological concentrations, we analysed the effects of two different coffee phenolic metabolites mixes consisting of compounds derived from bacterial metabolization reactions or phase II conjugations, as well as caffeic acid. The results showed that these mixes were able to counteract DEP-induced oxidative stress. The cellular components mediating the downregulation of ROS included extracellular signal-regulated kinase 1/2 (ERK1/2), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and uncoupling protein 2 (UCP2). Contrary to coffee phenolic metabolites, the treatment with N-acetylcysteine (NAC), a known antioxidant, was found to be ineffective in preventing the DEP exposure oxidant effect. These results revealed that coffee phenolic metabolites could be promising candidates to protect against some adverse health effects of daily exposure to air pollution.

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“…Catechin also inhibits complex I in isolated rat heart mitochondria and decreases H 2 O 2 generation [137]. Nobiletin decreases mitochondrial oxygen consumption and H 2 O 2 production in the presence of glutamate and malate, but a slight increase has been observed with succinate [138]. However, other reports have shown that the inhibition of complex I by an apple peel polyphenol extract leads to increased mitochondrial superoxide production [139].…”

Section: Flavonoids Attenuate Mitochondrial Ros Formationmentioning

confidence: 95%

Flavonoids and Mitochondria: Activation of Cytoprotective Pathways?

Kicińska

Jarmuszkiewicz

2020

Molecules

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A large number of diverse mechanisms that lead to cytoprotection have been described to date. Perhaps, not surprisingly, the role of mitochondria in these phenomena is notable. In addition to being metabolic centers, due to their role in cell catabolism, ATP synthesis, and biosynthesis these organelles are triggers and/or end-effectors of a large number of signaling pathways. Their role in the regulation of the intrinsic apoptotic pathway, calcium homeostasis, and reactive oxygen species signaling is well documented. In this review, we aim to characterize the prospects of influencing cytoprotective mitochondrial signaling routes by natural substances of plant origin, namely, flavonoids (e.g., flavanones, flavones, flavonols, flavan-3-ols, anthocyanidins, and isoflavones). Flavonoids are a family of widely distributed plant secondary metabolites known for their beneficial effects on human health and are widely applied in traditional medicine. Their pharmacological characteristics include antioxidative, anticarcinogenic, anti-inflammatory, antibacterial, and antidiabetic properties. Here, we focus on presenting mitochondria-mediated cytoprotection against various insults. Thus, the role of flavonoids as antioxidants and modulators of antioxidant cellular response, apoptosis, mitochondrial biogenesis, autophagy, and fission and fusion is reported. Finally, an emerging field of flavonoid-mediated changes in the activity of mitochondrial ion channels and their role in cytoprotection is outlined.

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Mitochondrial Target of Nobiletin's Action

Cited by 6 publications

References 49 publications

Nobiletin Alleviates Astrocyte Activation and Oxidative Stress Induced by Hypoxia In Vitro

Nobiletin Alleviates Astrocyte Activation and Oxidative Stress Induced by Hypoxia In Vitro

Study of the Antioxidant Effects of Coffee Phenolic Metabolites on C6 Glioma Cells Exposed to Diesel Exhaust Particles

Flavonoids and Mitochondria: Activation of Cytoprotective Pathways?

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