Nobiletin Regulates ROS/ADMA/DDAHII/eNOS/NO Pathway and Alleviates Vascular Endothelium Injury by Iron Overload

Wang, Zhiqing; Yang, Bin; Chen, Xuepiao; Zhou, Qing; Li, Hongwei; Chen, Shuping; Yin, Dong; He, Huan; He, Ming

doi:10.1007/s12011-020-02038-6

Cited by 19 publications

(14 citation statements)

References 49 publications

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“…The NOB is suggested to be a potential agent in fighting against iron overload. The administration of NOB inhibits mitochondrial-mediated apoptosis via reducing ROS generation to attenuate vascular endothelium injury caused by iron overload [69]. Interleukin-21 (IL-21), produced by stimulated CD4+ T immune cells [70], plays a significant role in the progression of rheumatoid arthritis (RA) via induction of inflammatory factors and matrix metalloproteinases (MMPs) such as MMP-3 and MMP-13 [71].…”

Section: Therapeutic and Biological Activities Of Nobmentioning

confidence: 99%

Nobiletin in Cancer Therapy: How This Plant Derived-Natural Compound Targets Various Oncogene and Onco-Suppressor Pathways

et al. 2020

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Cancer therapy is a growing field, and annually, a high number of research is performed to develop novel antitumor drugs. Attempts to find new antitumor drugs continue, since cancer cells are able to acquire resistance to conventional drugs. Natural chemicals can be considered as promising candidates in the field of cancer therapy due to their multiple-targeting capability. The nobiletin (NOB) is a ubiquitous flavone isolated from Citrus fruits. The NOB has a variety of pharmacological activities, such as antidiabetes, antioxidant, anti-inflammatory, hepatoprotective, and neuroprotective. Among them, the antitumor activity of NOB has been under attention over recent years. In this review, we comprehensively describe the efficacy of NOB in cancer therapy. NOB induces apoptosis and cell cycle arrest in cancer cells. It can suppress migration and invasion of cancer cells via the inhibition of epithelial-to-mesenchymal transition (EMT) and EMT-related factors such as TGF-β, ZEB, Slug, and Snail. Besides, NOB inhibits oncogene factors such as STAT3, NF-κB, Akt, PI3K, Wnt, and so on. Noteworthy, onco-suppressor factors such as microRNA-7 and -200b undergo upregulation by NOB in cancer therapy. These onco-suppressor and oncogene pathways and mechanisms are discussed in this review.

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Section: Therapeutic and Biological Activities Of Nobmentioning

confidence: 99%

Nobiletin in Cancer Therapy: How This Plant Derived-Natural Compound Targets Various Oncogene and Onco-Suppressor Pathways

et al. 2020

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“…In support of this observation, nobiletin has been shown to promote the phosphorylation of eNOS at position Ser-1177 by increasing endothelial [Ca 2+ ]i, thereby increasing NO production and vasodilation in phenylephrineprecontracted mesenteric arteries isolated from rats [34]. In keeping with these findings, nobiletin alleviated iron overload damage in vascular endothelium through increasing eNOS phosphorylation and NO production [35]. In addition, nobiletin was found to induce endothelium-independent vasodilation in rat aorta.…”

Section: Differential Effects Of Citrus Flavonoids On Enos Expressionmentioning

confidence: 52%

Nobiletin Protects Endothelial Cell Function via Upregulation of eNOS/ET-1 and Antioxidant Status-Related Genes under Nonstimulated and Inflammatory Conditions

Zhang

Pieri

et al. 2022

Journal of Food Quality

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Nobiletin, a natural polymethoxylated flavonoid compound, has been shown to exert a wide range of biological activities. However, there is limited evidence on the molecular mechanisms by which nobiletin modulates endothelial cell function. Our aim was to investigate the potential of nobiletin to enhance endothelial cell functionality under nonstimulated and inflammatory conditions. To this end, gene expression relevant to nitric oxide (NO) production, endothelin 1 (ET-1), and antioxidant status in human endothelial cells EA.hy926 was determined using real-time PCR. The fluorescence probe 4,5-diaminofluorescein (DAF-2) was used to measure NO production. The results demonstrated significant upregulation of eNOS and antioxidant genes as well as downregulation of ET-1 by nobiletin under nonstimulated and TNF-α-stimulated inflammatory conditions. These findings suggest a promising protective effect of nobiletin with relevance for cardiovascular health, likely through the NO/ET-1 dynamics and Nrf2 signaling pathway.

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“…Within a few minutes of exposure to ionization radiation (IR) and as ROS is generated in excessive amount, vascular protectant nitric oxide (NO) is eliminated, triggering nitrosylation of protein tyrosine residues and lipid peroxidation. Ultimately, vasomotor response is weakened, and vascular stenosis appears ( 53 , 54 ). After radiation, NADPH oxidases (NOXs), especially NOX2 and NOX4 that are abundantly expressed in vascular endothelial cells, are up-regulated.…”

Section: Discussionmentioning

confidence: 99%

Effect of Hydrogen Inhalation Therapy on Hearing Loss of Patients With Nasopharyngeal Carcinoma After Radiotherapy

Kong

Lü

et al. 2022

Front. Med.

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ObjectiveTo evaluate the clinical efficacy and safety of hydrogen inhalation in improving hearing loss in patients with long-term survival of nasopharyngeal carcinoma after radiotherapy.MethodsThe eustachian tube dysfunction score, pure tone air conduction threshold, bone conduction threshold, the score of tympanogram and otoscope were prospectively observed in patients with deafness after radiotherapy only or combined radiotherapy and chemotherapy for nasopharyngeal carcinoma. Paired t test and one-way analysis of variance were used to analyze the data before and after treatment.ResultsA total of 17 patients were observed. The median time from radiotherapy to now was 228 months, and the median time from the diagnose of deafness to now was 92 months. After 4 weeks of hydrogen inhalation, the score of eustachian tube dysfunction, air conduction and bone conduction hearing thresholds were significantly reduced, P values were 0.0293, 0.0027, 0.0404, respectively. The mean air-bone gap, the score of otoendoscopy and tympanogram were also decreased, but the differences were not significant (P = 0.2079, P = 0.0536, P = 0.1056). Patients with radiotherapy alone and concurrent chemo-radiotherapy had significantly lower air conduction hearing threshold after hydrogen absorption (P = 0.0142, P = 0.0495). The results of air and bone hearing thresholds before, 4 and 12 weeks after hydrogen inhalation showed a descending trend. The air and bone hearing thresholds before hydrogen inhalation were 74.69 ± 27.03 dB and 45.70 ± 21.58 dB, respectively. At the 12th week, the mean values of air and bone hearing thresholds were the lowest, which were 66.88 ± 20.88 dB and 40.94 ± 18.93 dB, respectively, but there was no significant difference in air and bone hearing thresholds among all groups (P = 0.6755, P = 0.7712). After hydrogen inhalation treatment, no adverse reactions such as nosebleed, chest pain, dyspnea, nausea, vomiting, dizziness, earache and allergic reaction were observed.ConclusionThis is the first prospective study on the effect of hydrogen inhalation on hearing improvement in patients with deafness after radiotherapy/chemotherapy for nasopharyngeal carcinoma, suggesting that continuous hydrogen inhalation may be an alternative rehabilitation therapy for these patients.

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Nobiletin Regulates ROS/ADMA/DDAHII/eNOS/NO Pathway and Alleviates Vascular Endothelium Injury by Iron Overload

Cited by 19 publications

References 49 publications

Nobiletin in Cancer Therapy: How This Plant Derived-Natural Compound Targets Various Oncogene and Onco-Suppressor Pathways

Nobiletin in Cancer Therapy: How This Plant Derived-Natural Compound Targets Various Oncogene and Onco-Suppressor Pathways

Nobiletin Protects Endothelial Cell Function via Upregulation of eNOS/ET-1 and Antioxidant Status-Related Genes under Nonstimulated and Inflammatory Conditions

Effect of Hydrogen Inhalation Therapy on Hearing Loss of Patients With Nasopharyngeal Carcinoma After Radiotherapy

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