Dietary naringenin supplementation attenuates experimental autoimmune encephalomyelitis by modulating autoimmune inflammatory responses in mice

Wang, Junpeng; Qi, Ying; Niu, Xinli; Tang, Hua; Meydani, Simin Nikbin; Wu, Dayong

doi:10.1016/j.jnutbio.2017.12.004

Cited by 56 publications

(33 citation statements)

References 46 publications

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“…Citrus extract (CE) has various biological functions, including anti-cancer [5], anti-bacterial [6,7], anti-oxidant [7,8], and anti-inflammatory [9,10]. Its strong anti-oxidant and anti-inflammatory effects are especially valuable in improving animal health [9,11]. Animal experiments have shown that orange peel extract improved immune response and disease resistance of broilers without affecting their average daily gain (ADG), average daily feed intake (ADFI), and feed conversion rate [12].…”

Section: Introductionmentioning

confidence: 99%

Citrus Extract Improves the Absorption and Utilization of Nitrogen and Gut Health of Piglets

Cui

Tian

Wang

et al. 2020

Animals

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The purpose of this study was to investigate the effects of citrus extract (CE) on plasma free amino acids, intestinal morphology and enzymes activity, fecal nitrogen and phosphorus emissions in piglets. The experiment was performed on 144 weaned piglets (Duroc × Landrace × Large White) divided into three groups. Control (CON), fed a basic diet; Antibiotic (ANTI), fed a basic diet supplemented with 75 g/t chlortetracycline; Citrus extract (CE), fed a basic diet supplemented with 300 mL/t CE. The albumin content of the CE group was significantly higher than the CON group. Compared with the CON and ANTI groups, the CE group had increased concentrations of plasma total essential amino acids and threonine. Compared with the CON group, CE increased the α-aminoadipic acid concentration, while compared with ANTI group, it increased the 3-methylhistidine concentration. Compared with the CON group, the crypt depth of duodenum, jejunum and ileum decreased, and the ratio of villus height to crypt depth of ileum increased in the ANTI and CE groups. CE increased the activity of alkaline phosphatase and lipase in duodenum, and the activity of alkaline phosphatase and trypsin in jejunum. In brief, CE improved the absorption and utilization of nitrogen, intestinal morphology and digestive enzymes activity.

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Section: Introductionmentioning

confidence: 99%

Citrus Extract Improves the Absorption and Utilization of Nitrogen and Gut Health of Piglets

Cui

Tian

Wang

et al. 2020

Animals

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“…Mice were fed a diet supplemented with 0.5% naringenin and then immunized to induce EAE as described before ( 9 ). At day 42, mice were killed, and plasma was collected to measure soluble IL-6Rα (sIL-6R) and soluble gp130 (sgp130) as described below.…”

Section: Methodsmentioning

confidence: 99%

“…Naringenin, a major flavanone in grapefruits, has a wide range of anti-inflammatory and neuro-protective properties ( 8 ). We recently reported that dietary naringenin supplementation ameliorated experimental autoimmune encephalomyelitis (EAE) in mice, which was associated with the decrease in Th1 and Th17 cell populations and pro-inflammatory cytokine IL-6 production, which promotes CD4 + T cells differentiation into Th17 cells ( 9 ). In addition, our in vitro study showed that naringenin directly inhibited effector T cell functions, including T cell proliferation, cell division, and production of cytokines IL-6, IFN-γ, and IL-17, in normal and EAE mice ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

Naringenin Modifies the Development of Lineage-Specific Effector CD4+ T Cells

Wang

Niu

et al. 2018

Front. Immunol.

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Disrupted balance in the lineages of CD4+ T cell subsets, including pro-inflammatory T helper (Th) cells and anti-inflammatory regulatory T cells (Treg), is a primary pathogenic factor for developing autoimmunity. We have found that this immunomodulatory effect of naringenin on effector T cells and T-cell mediated experimental autoimmune encephalomyelitis (EAE). We therefore explored the effects of naringenin on the development of different effector CD4+ T cells. Naïve CD4+ T cells were differentiated under respective Th1, Th2, Th17, and Treg polarizing conditions with naringenin. Percent populations of each differentiated CD4+ T cell subsets were determined and the corresponding regulating pathways were investigated as underlying mechanisms. Naringenin mainly inhibited CD4+ T cell proliferation and differentiation to Th1 and Th17, but did not affect Th2 cells. Impeded Th1 polarization was associated with inhibition of its specific regulator proteins T-bet, p-STAT1, and p-STAT4 by naringenin. Likewise, Th17 regulator proteins RORγt, p-STAT3, and Ac-STAT3 were also inhibited by naringenin. In addition, naringenin promoted Treg polarization and also prevented IL-6-induced suppression of Treg development via down-regulation of p-Smad2/3 as well as inhibition of IL-6 signaling, and the latter was further supported by the in vivo results showing lower soluble IL-6R but higher soluble gp130 levels in plasma of naringenin-fed compared to the control EAE mice. Naringenin impacts CD4+ T cell differentiation in a manner that would explain its beneficial effect in preventing/mitigating T cell-mediated autoimmunity.

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“…In addition, naringenin influenced immune cell infiltration and function in several disease models. Naringenin reduced T cell infiltration in skin lesions of an atopic dermatitis model and in the spinal cord of an encephalomyelitis model [12,13]. Naringenin also reduced neutrophil infiltration in the peritoneal cavity of lipopolysaccharideinduced hyperalgesia and in the bronchoalveolar lavage fluid of lipopolysaccharide-induced lung injury [14,15].…”

Section: Introductionmentioning

confidence: 98%

Naringenin suppresses neutrophil infiltration into adipose tissue in high-fat diet-induced obese mice

et al. 2019

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Recruitment of immune cells to adipose tissue is altered dramatically in obesity, which results in chronic inflammation of the adipose tissue that leads to metabolic disorders, such as insulin resistance and type 2 diabetes mellitus. The regulation of immune cell infiltration into adipose tissue has prophylactic and therapeutic implications for obesity-related diseases. We previously showed that naringenin, a citrus flavonoid, suppressed macrophage infiltration into adipose tissue by inhibiting monocyte chemoattractant protein-1 (MCP-1) expression in the progression phase to high-fat diet (HFD)-induced obesity.In the current study, we evaluated the effects of naringenin on neutrophil infiltration into adipose tissue, because neutrophils also infiltrate into adipose tissue in the progression phase to obesity. Naringenin suppressed neutrophil infiltration into adipose tissue induced by the short-term (2 weeks) feeding of a HFD to mice. Naringenin tended to inhibit the HFD-induced expression of several chemokines, including MCP-1 and MCP-3, in adipose tissue. Naringenin also inhibited MCP-3 expression in 3T3-L1 adipocytes and a co-culture of 3T3-L1 adipocytes and RAW264 macrophages. However, naringenin did not affect the expression of macrophage inflammatory protein-2 (MIP-2), an important chemokine for neutrophil migration and activation, in macrophages or in a co-culture of adipocytes and macrophages. Our results suggest that naringenin suppresses neutrophil infiltration into adipose tissue via the regulation of MCP-3 expression and macrophage infiltration.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Dietary naringenin supplementation attenuates experimental autoimmune encephalomyelitis by modulating autoimmune inflammatory responses in mice

Cited by 56 publications

References 46 publications

Citrus Extract Improves the Absorption and Utilization of Nitrogen and Gut Health of Piglets

Citrus Extract Improves the Absorption and Utilization of Nitrogen and Gut Health of Piglets

Naringenin Modifies the Development of Lineage-Specific Effector CD4+ T Cells

Naringenin suppresses neutrophil infiltration into adipose tissue in high-fat diet-induced obese mice

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