Endothelium-independent vasodilator effects of nobiletin in rat aorta

Kaneda, Hisako; Otomo, Rieko; Sasaki, Noriyuki; Omi, Toshinori; Sato, T; Kaneda, Toshio

doi:10.1016/j.jphs.2019.04.004

Cited by 11 publications

(11 citation statements)

References 23 publications

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“…Among the investigated citrus flavonoids in the present study, nobiletin was the most effective compound in increasing eNOS mRNA and NO production under the defined conditions. Consistent with these results, nobiletin significantly increased the relaxation of phenylephrine-induced contraction in endothelium-intact rat aorta [33]. 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].…”

Section: Differential Effects Of Citrus Flavonoids On Enos Expressionsupporting

confidence: 73%

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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Section: Differential Effects Of Citrus Flavonoids On Enos Expressionsupporting

confidence: 73%

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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“…The interest directed towards NOB emanates from its efficacy in the treatment of different diseases. Studies have demonstrated that NOB has a variety of therapeutic and biological activities, including antidiabetic [49], antioxidant [50], osteoprotective [51], anti-inflammatory [52], hepatoprotective [53], cardioprotective [54,55], and neuroprotective [56], as well as improving metabolic disorders [57]. Notably, recent studies have shown the role of molecular signaling pathways involved in the protective effects of NOB in various diseases.…”

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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“…The most abundant PMF occurring in CSP, Nobiletin 53, was proven to possess sevral bioactivities, such as antioxidant, anti-inflammatory, cancer preventive [64] and also a significant protective effect in vivo against the endotoxic shock [65] and ethanol-induced acute gastric lesions [66] in mice. Further, compound 53 demonstrated the capacity to induce autophagy in human keratinocyte HaCaT cells [67], vasodilatator effect in the rat aorta [68] and to protect the intestinal barrier from the demages induced by dextran sulfate sodium [69]. PMFs can be considered as especially promising lead compounds for cancer therapy as asignificant cytotoxic activity has been demonstrated toward a number of cancer cells [70,71] with several mechanisms of action [72,73]; the cytotypes investigated include MCF-7 [73][74][75][76], Hs578T triple-negative breast cancer [73,77]; colon cancer cells CaCo-2 [19], LoVo [78], HTC-116 [79,80] and HT-29 [79,81]; lung cancer cells A549 [80,82], H460 [82,83], H1299 [82,83]; gastric cancer cell lines AGS, BGC-823, and SGC-7901 [84]; leukemia cells HL-60 [85].…”

Section: Flavanoidsmentioning

confidence: 99%

The Orange Peel: An Outstanding Source of Chemical Resources

Fontana¹

2021

Citrus - Research, Development and Biotechnology

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Citrus sinensis (L.) Osbeck is a very common cultivar belonging to the Rutaceae family. It is largely diffused in several areas of the world characterized by mild to warm climate conditions. Its abundant worldwide production (up to 107 Tons. per year) and consumption both as the edible part of the fruit and as several types of derivative products imply the production of a huge amount of waste, such as the fruit pomace. Several ways of recycling this material have been developed in recent years: employment as fertilizer, fodder ingredient, and even cloth material. However, the chemical added value of Citrus sinensis peel has been underestimated despite the diversified and significant content of useful chemicals, such as polyphenols, polymethoxylated phenols, glycosylated flavonoids, volatile and non-volatile terpenoids, pectins, enzymes, etc. This work aims to highlight the outstanding chemical potential of Citrus sinensis peel.

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Endothelium-independent vasodilator effects of nobiletin in rat aorta

Cited by 11 publications

References 23 publications

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

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

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

The Orange Peel: An Outstanding Source of Chemical Resources

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