Protective effects of nobiletin on cisplatin induced neurotoxicity in rats

Kazak, Filiz; Akalın, Pınar Peker; Yarım, Gül Fatma; Başpınar, Nuri; Özdemir, Özgür; Ateş, Mehmet Burak; Altuğ, Muhammed Enes; Deveci, Mehmet Zeki Yılmaz

doi:10.1080/00207454.2021.1896507

Cited by 11 publications

(7 citation statements)

References 41 publications

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“…In a rat model of cisplatin-induced neurotoxicity, it also reduced cisplatin-induced apoptosis in the cerebrovascular endothelium and neurons. Thus, nobiletin might be considered as a supplement to cisplatin therapy for cancer patients [ 42 ]. Our results showed a substantial reduction in the reactive oxygen species and an amelioration of the mitochondrial membrane potential in the co-exposure group (NA + NOB) in comparison to the NA-exposed group.…”

Section: Discussionmentioning

confidence: 99%

Nobiletin Ameliorates Cellular Damage and Stress Response and Restores Neuronal Identity Altered by Sodium Arsenate Exposure in Human iPSCs-Derived hNPCs

et al. 2022

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Environmental exposure to arsenic has been profoundly associated with chronic systemic disorders, such as neurodegeneration, in both experimental models and clinical studies. The neuronal cells of the brain and the nervous system have a limited regeneration capacity, thus making them more vulnerable to exposure to xenobiotics, leading to long-lasting disabilities. The functional and anatomical complexity of these cells hinders the complete understanding of the mechanisms of neurodegeneration and neuroprotection. The present investigations aimed to evaluate the neuroprotective efficacy of a herbal formulation of Nobiletin (NOB) against the toxic insult induced by sodium arsenate (NA) in human neural progenitor cells (hNPCs) derived from human induced pluripotent stem cells (hiPSCs). Prior to the neuroprotective experiments, biologically safe doses of both NOB and NA were ascertained using standard endpoints of cytotoxicity. Thereafter, the hNPCs were exposed to either NOB (50 μM) or NA (50 μM) and co-exposed to biologically safe concentrations of NA (50 μM) with NOB (50 μM) for a period of up to 48 h. NOB treatment restored the morphological damage (neurite damage), the levels of stress granule G3BP1 (Ras-GTPase-activating protein (SH3 domain)-binding protein) and TIA1 (T cell-restricted intracellular antigen), and the expression of neuronal markers (Tuj1, Nestin, MAP2, and PAX6) when compared to NA-exposed cells. A substantial restoration of reactive oxygen species and mitochondrial membrane potential was also witnessed in the co-exposure group (NA + NOB) in comparison to the NA-exposed group. The findings suggest that NOB possesses a significant restorative/protective potential against the NA challenge in hNPCs under experimental conditions and imply that nobiletin may impart a potential therapeutic impact if studied adequately using in vivo studies.

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Section: Discussionmentioning

confidence: 99%

Nobiletin Ameliorates Cellular Damage and Stress Response and Restores Neuronal Identity Altered by Sodium Arsenate Exposure in Human iPSCs-Derived hNPCs

et al. 2022

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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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“… 6 w LPS-induced neuroinflammation iNOS↓, IL-6 ↓, JAK2↓, TNF↓, IL-1↓, and NF-κB↓ STAT3 phosphorylation ↓ [ 63 ] 6.25, 12.5, 25 or 50 μg/ml 24 h LPS-stimulated BV-2 microglia NO↓, iNOS↓, IL-6↓, JAK2↓, TNFα↓, IL-1β↓, and NF-κB ↓ [ 57 ] 10, 20 or 40 μM 24 h H2O2-induced oxidative stress in astrocytes Ose-regulated protein(GRP) 78 ↑, Cell death ↓ Endoplasmic reticulum (ER) stress lead ↓ [ 21 ] 30, 50, 100 or 200 μM 10 min Glutamate-stimulated neurons Calcium overload ↓ ROS ↓ Mitochondrial depolarization ↑ [ 31 ] 1, 10 or 30 µM 5 min Neurons ROS↓, apoptotic signalling↓, ATP production ↑, Neuronal viability↑, Nrf2↓, HO-1↓ [ 3 ] 10 mg/kg (i.p.) 9 d Cisplatin-induced nerve injury Peroxide↓, apoptotic↓ [ 25 ] 50 µM 96 h Sodium arsenate-induced neural progenitor cells toxic Neuronal degeneration ↓, Oedema ↓, caspase-3↓ BDNF ↑, G6PD activity ↑ Antioxidant ↑, Antiapoptotic ↑ Neuroprotective effects ↑ [ 42 ] …”

Section: Effect and Mechanisms Of Nobiletin In The Cnsmentioning

confidence: 99%

A review on recent advances on nobiletin in central and peripheral nervous system diseases

Pang,

Xiong,

et al. 2023

Eur J Med Res

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In recent years, the role of nobiletin in neuronal disorders has received extensive attention. However, the study of nobiletin in the peripheral nervous system is limited. Nobiletin, as a compound with high fat solubility, high bioavailability and low toxicity, has been extensively studied. Accumulating scientific evidence has shown that nobiletin has a variety of biological functions in the nervous system, such as inhibiting the expression of inflammatory factors, reducing the neurotoxic response, improving the antioxidant capacity, promoting the survival of nerve cells, promoting axon growth, reducing blood‒brain barrier permeability, reducing brain oedema, promoting cAMP response element binding protein expression, improving memory, and promoting mild depolarization of nerve cell mitochondria to improve antioxidative stress capacity. Accumulating studies have shown that nobiletin also protects enteric nervous system, spinal cord and sciatic nerve. To explore the new therapeutic potential of nobiletin in the nervous system, recent and relevant research progress is reviewed in this article. This will provide a new research idea for nobiletin in the nervous system.

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Protective effects of nobiletin on cisplatin induced neurotoxicity in rats

Cited by 11 publications

References 41 publications

Nobiletin Ameliorates Cellular Damage and Stress Response and Restores Neuronal Identity Altered by Sodium Arsenate Exposure in Human iPSCs-Derived hNPCs

Nobiletin Ameliorates Cellular Damage and Stress Response and Restores Neuronal Identity Altered by Sodium Arsenate Exposure in Human iPSCs-Derived hNPCs

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

A review on recent advances on nobiletin in central and peripheral nervous system diseases

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