Nobiletin acts anti-inflammatory on murine IL-10−/− colitis and human intestinal fibroblasts

Hagenlocher, Yvonne; Gommeringer, Sonja; Held, A; Feilhauer, Katharina; Köninger, Jörg; Bischoff, Stephan C.; Lorentz, Axel

doi:10.1007/s00394-018-1661-x

Cited by 39 publications

(31 citation statements)

References 52 publications

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“…Later, the same research group further investigated the impact of nobiletin on in vivo IL-10 −/− mice model. Evidence showed that nobiletin treated mice exhibit significant reduction in colitis clinical symptoms, mast cell numbers, mast cell degranulation and cellular infiltration (Hagenlocher et al, 2018), which may provide very useful reference for clinical application of nobiletin. Wang et al…”

Section: Inflammatory Bowel Diseasesmentioning

confidence: 96%

Anti-inflammatory effects of polymethoxyflavones from citrus peels: a review

Wang¹,

Li²,

Wei³

et al. 2018

Journal of Food Bioactives

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Inflammation is a non-specific kind of biological immune response of body tissues to any type of external or internal injuries, such as pathogens, irritants and immune stress reactions. There are two types of inflammation, namely acute and chronic. Acute inflammation starts and develops rapidly, and is aroused by various factors, including injuries, infection, toxins or immune reactions. Chronic inflammation usually lasts for an extended long period of time and results from elimination failure of acute inflammation, autoimmune disorders, various pathogens and pathogenic environments. Except for the damage itself, there exists a direct and intimate connection between chronic inflammation and various clinic common diseases, such as neurodegeneration, as well as metabolic and cardiovascular ailments. Citrus peel is a by-product generated in citrus juice processing. Polymethoxyflavones (PMFs) exist abundantly and almost exclusively in citrus peels, and their biological activities have been broadly investigated in recent years. PMFs have proven to possess potential inhibitory bioactivities towards a number of functional and immune diseases including inflammation. The two most abundant PMFs exhibiting prominent bioactivities in citrus peels are nobiletin and tangeretin, ubiquitously detected in various citrus species. In this review, the beneficial health effects and the underlying molecular mechanisms of ten main citrus PMFs were illustrated against numerous inflammatory diseases, including inflammatory bowel disease (IBD), neuroinflammation and organ inflammation, among others.

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Section: Inflammatory Bowel Diseasesmentioning

confidence: 96%

Anti-inflammatory effects of polymethoxyflavones from citrus peels: a review

Wang¹,

Li²,

Wei³

et al. 2018

Journal of Food Bioactives

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“…People enjoy unique varieties of citrus because of their refreshing flavor and nutritional value. Citrus natural products, especially the flavonoids, have become a hot research topic because of their diverse biological activities [1,2,3]. Polymethoxyflavones (PMFs) are an essential type of flavonoids in citrus, characterized by more than or equal to four methoxy substitutions in the structure.…”

Section: Introductionmentioning

confidence: 99%

Three Polymethoxyflavones Purified from Ougan (Citrus reticulata Cv. Suavissima) Inhibited LPS-Induced NO Elevation in the Neuroglia BV-2 Cell Line via the JAK2/STAT3 Pathway

Wang

Zang

et al. 2019

Nutrients

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In order to establish an efficient method for separation of polymethoxyflavones (PMFs) and explore the anti-inflammatory mechanism of PMF monomers, a citrus variety rich in PMFs, Ougan (Citrus reticulata cv. Suavissima), was selected, and three monomers, including nobiletin, tangeretin, and 5-demethylnobiletin, were purified by ultrasonic-assisted extraction, solid phase extraction, and high-speed countercurrent chromatography separation. UPLC-MS was used to identify the three monomers. UPLC determined purities of 99.87% to nobiletin, 99.76% to tangeretin, and 98.75% to 5-demethylnobiletin with the standard curve method. A lipopolysaccharide (LPS)-induced NO releasing model was performed in the mouse microglia BV-2 cell line. Results illustrated that PMF monomers inhibited the NO release and the inflammation-related cytokines, including IL-1β, IL-6, and TNFα elevation. QRT-PCR revealed that PMFs alleviated LPS-induced upregulation of iNOS, IL-6, JAK2, TNFα, IL-1β, and NF-κB and LPS-induced downregulation of IκBα, while they did not affect TLR1, TLR2, TLR4, and TLR6. STAT3 expression was repressed by tangeretin and 5-demethylnobiletin, but not by nobiletin. Western blot assay also showed a suppression of expression and phosphorylation of JAK2 by all three PMF monomers, while STAT3 phosphorylation was restrained by tangeretin and 5-demethylnobiletin. The mechanism was primarily verified by the JAK2 inhibitor Ruxolitinib and the STAT3 inhibitor Stattic.

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“…In the murine IL-10 knockout model of colitis, treatment with the citrus flavonoid nobiletin resulted in a reduction of clinical colitis and a reduction of mast cell number and degranulation, which correlated positively with disease activity indexes [ 179 ].…”

Section: Nutraceuticals Affecting Mast Cell Activitymentioning

confidence: 99%

Mast Cell Regulation and Irritable Bowel Syndrome: Effects of Food Components with Potential Nutraceutical Use

2020

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Mast cells are key actors in inflammatory reactions. Upon activation, they release histamine, heparin and nerve growth factor, among many other mediators that modulate immune response and neuron sensitization. One important feature of mast cells is that their population is usually increased in animal models and biopsies from patients with irritable bowel syndrome (IBS). Therefore, mast cells and mast cell mediators are regarded as key components in IBS pathophysiology. IBS is a common functional gastrointestinal disorder affecting the quality of life of up to 20% of the population worldwide. It is characterized by abdominal pain and altered bowel habits, with heterogeneous phenotypes ranging from constipation to diarrhea, with a mixed subtype and even an unclassified form. Nutrient intake is one of the triggering factors of IBS. In this respect, certain components of the daily food, such as fatty acids, amino acids or plant-derived substances like flavonoids, have been described to modulate mast cells’ activity. In this review, we will focus on the effect of these molecules, either stimulatory or inhibitory, on mast cell degranulation, looking for a nutraceutical capable of decreasing IBS symptoms.

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Nobiletin acts anti-inflammatory on murine IL-10−/− colitis and human intestinal fibroblasts

Abstract: Nobiletin decreases inflammatory symptoms and markers in murine colitis as well as fibrotic collagen deposition and expression. Thus, nobiletin could be a potential new agent in therapy of chronic colitis.

Cited by 39 publications

References 52 publications

Anti-inflammatory effects of polymethoxyflavones from citrus peels: a review

Anti-inflammatory effects of polymethoxyflavones from citrus peels: a review

Three Polymethoxyflavones Purified from Ougan (Citrus reticulata Cv. Suavissima) Inhibited LPS-Induced NO Elevation in the Neuroglia BV-2 Cell Line via the JAK2/STAT3 Pathway

Mast Cell Regulation and Irritable Bowel Syndrome: Effects of Food Components with Potential Nutraceutical Use

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