Urolithins, gut microbiota‐derived metabolites of ellagitannins, inhibit LPS‐induced inflammation in RAW 264.7 murine macrophages

Piwowarski, Jakub P.; Kiss, Anna K.; Granica, Sebastian; Moeslinger, Thomas

doi:10.1002/mnfr.201500264

Cited by 107 publications

(77 citation statements)

References 48 publications

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“…One unequivocal response we routinely observed upon UroA administration was the remarkable suppression of inflammation . In particular, we saw a significant reduction in the expression of proinflammatory markers, cytokines, and chemokines in liver, adipose, and macrophages of UroA‐injected mice (Figures , , and ).…”

Section: Discussionmentioning

confidence: 75%

Urolithin A, a Gut Metabolite, Improves Insulin Sensitivity Through Augmentation of Mitochondrial Function and Biogenesis

Toney

Fan

Xian

et al. 2019

Obesity

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Objective Urolithin A (UroA) is a major metabolite of ellagic acid produced following microbial catabolism in the gut. Emerging evidence has suggested that UroA modulates energy metabolism in various cells. However, UroA’s physiological functions related to obesity and insulin resistance remain unclear. Methods Male mice were intraperitoneally administrated either UroA or dimethyl sulfoxide (vehicle) along with a high‐fat diet for 12 weeks. Insulin sensitivity was evaluated via glucose and insulin tolerance tests and acute insulin signaling. The effects of UroA on hepatic triglyceride accumulation, adipocyte size, mitochondrial DNA content, and proinflammatory gene expressions were determined. The impact of UroA on macrophage polarization and mitochondrial respiration were assessed in bone marrow–derived macrophages. Results Administration of UroA (1) improved systemic insulin sensitivity, (2) attenuated triglyceride accumulation and elevated mitochondrial biogenesis in the liver, (3) reduced adipocyte hypertrophy and macrophage infiltration into the adipose tissue, and (4) altered M1/M2 polarization in peritoneal macrophages. In addition, UroA favored macrophage M2 polarization and mitochondrial respiration in bone marrow‐derived macrophages. Conclusions UroA plays a direct role in improving systemic insulin sensitivity independent of its parental compounds. This work supports UroA’s role in the metabolic benefits of ellagic acid–rich foods and highlights the significance of its microbial transformation in the gut.

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Section: Discussionmentioning

confidence: 75%

Urolithin A, a Gut Metabolite, Improves Insulin Sensitivity Through Augmentation of Mitochondrial Function and Biogenesis

Toney

Fan

Xian

et al. 2019

Obesity

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“…Additionally, a recent study further confirms the protective effect urolithins have over intestinal inflammation using RAW 264.7 murine macrophages as a model (Piwowarski et al, 2015). Urolithins A, B and C decreased NO production via inhibition of the iNOS protein, and expression of IL-1β, TNF-α and IL-6 (Piwowarski et al, 2015).…”

Section: Accepted Manuscriptmentioning

confidence: 74%

Health benefits of walnut polyphenols: An exploration beyond their lipid profile

Sánchez-González

Ciudad

Noé

et al. 2017

Critical Reviews in Food Science and Nutrition

125

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Walnuts are commonly found in our diet and have been recognized for their nutritious properties for a long time. Traditionally, walnuts have been known for their lipid profile which has been linked to a wide array of biological properties and health-promoting effects. In addition to essential fatty acids, walnuts contain a variety of other bioactive compounds such as, vitamin E and polyphenols. Among common foods and beverages, walnuts represent one of the most important sources of polyphenols, hence, their effect over human health warrants attention. The main polyphenol in walnuts is pedunculagin, an ellagitannin. After consumption, ellagitannins are hydrolyzed to release ellagic acid, which is converted by gut microflora to urolithin A and

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“…NO helps macrophages with immunological activity rebuff etiologic agents. 4) iNOS is an enzyme that produces NO when induced by lipopolysaccharide (LPS) or various pro-inflammatory cytokines and a high level of human iNOS is measured in macrophages from patients who have infections or inflammatory diseases.…”

Section: )mentioning

confidence: 99%

“…4) Inflammatory bowel diseases including ulcerative colitis (UC) and Crohn's disease (CD) are chronic relapsing disorders of the gastrointestinal tract characterized pathologically by epithelial injury and intestinal inflammation.…”

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confidence: 99%

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Triterpenoids Isolated from <i>Alnus japonica</i> Inhibited LPS-Induced Inflammatory Mediators in HT-29 Cells and RAW264.7 Cells

Lee

Shim

Sung

2017

Biological & Pharmaceutical Bulletin

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Alnus japonica (Betulaceae) is a broad-leaved tree easily found in damp regions within the mountains of Korea and Japan. Four triterpenoids (1-4) from the fruits of A. japonica, including the newly isolated 3β-hydroxy-lanost-9(11),23(24)-dien-25,26-diol (3), inhibited the lipopolysaccharide (LPS)-induced expression of the chemotactic cytokine interleukin (IL)-8 and nitric oxide (NO) production in HT-29 colon epithelial cells and RAW264.7 macrophages, respectively. Among these triterpenoids, compound 4, which showed the most potent inhibitory activity, effectively down-regulated LPS-induced protein expression of inducible nitric oxide synthase (iNOS) in RAW264.7 cells and in HT-29 cells. Also, compound 4 concentration-dependently inhibited the levels of LPS-induced pro-inflammatory cytokines, IL-1β and IL-6 in macrophage cells. These triterpenoids isolated from A. japonica fruits are thought to contribute to the anti-inflammatory activities of macrophage and colon epithelial cells, which are important for regulating the colon immune system. They are expected to be potential candidates for therapeutic agents against inflammatory bowel disease.

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Urolithins, gut microbiota‐derived metabolites of ellagitannins, inhibit LPS‐induced inflammation in RAW 264.7 murine macrophages

Abstract: The anti-inflammatory effects of urolithins at concentrations that are physiologically relevant for gut tissues (≥40 μM), as revealed in this study, support the data from in vivo studies showing the beneficial effects of ellagitannin-rich products toward intestinal inflammation.

Cited by 107 publications

References 48 publications

Urolithin A, a Gut Metabolite, Improves Insulin Sensitivity Through Augmentation of Mitochondrial Function and Biogenesis

Urolithin A, a Gut Metabolite, Improves Insulin Sensitivity Through Augmentation of Mitochondrial Function and Biogenesis

Health benefits of walnut polyphenols: An exploration beyond their lipid profile

Triterpenoids Isolated from <i>Alnus japonica</i> Inhibited LPS-Induced Inflammatory Mediators in HT-29 Cells and RAW264.7 Cells

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