Nobiletin Exhibits Neuroprotective Effects against Mitochondrial Complex I Inhibition via Regulating Apoptotic Signaling

Amarsanaa, Khulan; Kim, Hye-Ji; Ko, Eun-A; Jo, Jaemin; Jung, Sung-Cherl

doi:10.5607/en20051

Cited by 24 publications

(20 citation statements)

References 57 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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“…Nobiletin (NOB) is the active monomer isolated from CRP, with the molecular formula C 21 H 22 O 8 (the chemical structure is shown in Figure 1(a) ). NOB has been reported to possess anti-inflammatory [ 11 ], antiapoptotic [ 12 ], and antineurotoxic [ 13 ] functions. In the cardiovascular system, NOB has been reported to attenuate adverse cardiac remodeling in rats following MI by restoring autophagy flux [ 14 ] and regulating c-Jun N-terminal kinase (JNK) [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Nobiletin Attenuates Pathological Cardiac Remodeling after Myocardial Infarction via Activating PPARγ and PGC1α

et al. 2021

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Rationale. Pathological cardiac remodeling serves as a vital mechanism during the progression from myocardial infarction (MI) to chronic heart failure (CHF). Nobiletin (NOB), an active monomer extracted from the peel of citrus fruit, has been reported to have beneficial effects in cardiovascular diseases. Our study was aimed at describing the specific mechanisms through which NOB protects against pathological cardiac remodeling after MI. Materials and Methods. C57BL/6 mice were treated with coronary artery ligation to generate an MI model, followed by treatment for 3 weeks with NOB (50 mg/kg/d) or vehicle (50 mg/kg/d), with or without the peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor T0070907 (1 mg/kg/d). Cardiac function (echocardiography, survival rate, Evans blue, and triphenyl tetrazolium chloride staining), fibrosis (Masson’s trichrome staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot (WB)), hypertrophy (haematoxylin-eosin staining, wheat germ agglutinin staining, and qRT-PCR), and apoptosis (WB and terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining) were evaluated. Hypoxia-induced apoptosis (TUNEL, WB) and phenylephrine- (PE-) induced pathological hypertrophy (immunofluorescence staining, qRT-PCR) models were established in primary neonatal rat ventricular myocytes (NRVMs). The effects of NOB with or without T0070907 were examined for the expression of PPARγ and PPARγ coactivator 1α (PGC1α) by WB in mice and NRVMs. The potential downstream effectors of PPARγ were further analyzed by WB in mice. Results. Following MI in mice, NOB intervention enhanced cardiac function across three predominant dimensions of pathological cardiac remodeling, which reflected in decreasing cardiac fibrosis, apoptosis, and hypertrophy decompensation. NOB intervention also alleviated apoptosis and hypertrophy in NRVMs. NOB intervention upregulated PPARγ and PGC1α in vivo and in vitro. Furthermore, the PPARγ inhibitor abolished the protective effects of NOB against pathological cardiac remodeling during the progression from MI to CHF. The potential downstream effectors of PPARγ were nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1). Conclusions. Our findings suggested that NOB alleviates pathological cardiac remodeling after MI via PPARγ and PGC1α upregulation.

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“…The induced effect was related to the downregulation of translocation of AIF, and the upregulation of complex I activity, and the expression of antioxidant factors such as Nrf2 and heme oxygenase 1 (HO-1). Based on the acquired data, this study suggested that nobiletin might have promising neuroprotective action against neurodegenerative diseases such as AD and PD [155].…”

Section: Neurodegenerative Disordersmentioning

confidence: 87%

Protective Effects of Flavonoids Against Mitochondriopathies and Associated Pathologies: Focus on the Predictive Approach and Personalized Prevention

Koklesová

Líšková

Samec

et al. 2021

IJMS

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Multi-factorial mitochondrial damage exhibits a “vicious circle” that leads to a progression of mitochondrial dysfunction and multi-organ adverse effects. Mitochondrial impairments (mitochondriopathies) are associated with severe pathologies including but not restricted to cancers, cardiovascular diseases, and neurodegeneration. However, the type and level of cascading pathologies are highly individual. Consequently, patient stratification, risk assessment, and mitigating measures are instrumental for cost-effective individualized protection. Therefore, the paradigm shift from reactive to predictive, preventive, and personalized medicine (3PM) is unavoidable in advanced healthcare. Flavonoids demonstrate evident antioxidant and scavenging activity are of great therapeutic utility against mitochondrial damage and cascading pathologies. In the context of 3PM, this review focuses on preclinical and clinical research data evaluating the efficacy of flavonoids as a potent protector against mitochondriopathies and associated pathologies.

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Nobiletin Exhibits Neuroprotective Effects against Mitochondrial Complex I Inhibition via Regulating Apoptotic Signaling

Cited by 24 publications

References 57 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

Nobiletin Attenuates Pathological Cardiac Remodeling after Myocardial Infarction via Activating PPARγ and PGC1α

Protective Effects of Flavonoids Against Mitochondriopathies and Associated Pathologies: Focus on the Predictive Approach and Personalized Prevention

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