Urolithin A attenuates ox‐LDL‐induced endothelial dysfunction partly by modulating microRNA‐27 and ERK/PPAR‐γ pathway

Han, Qinghua; Yan, Chunhong; Wang, Lingfang; Li, Guanghui; Xu, Yunfeng; Xia, Xiaodong

doi:10.1002/mnfr.201500827

Cited by 47 publications

(42 citation statements)

References 58 publications

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“…In this context, we recently showed that urolithins are able to reduce the pro-inflammatory response to high glucose levels in cultured neonatal cardiomyocytes and fibroblasts [13], suggesting that they can prevent the diabetes-induced microenvironmental changes triggering myocardial inflammation and functional impairment in the diabetic heart. These findings confirmed previous in vitro studies demonstrating the positive role of urolithin supplementation in different cell models, including anti-inflammatory activity in endothelial cells and macrophages [15, 32–36] and beneficial effects on lipid metabolism in adipocytes and hepatocytes [37]. However, the biological effects of in vivo urolithin administration in the setting of diabetes, as well as in other pathological conditions, remain to be characterized [38].…”

Section: Discussionsupporting

confidence: 87%

In vivo administration of urolithin A and B prevents the occurrence of cardiac dysfunction in streptozotocin-induced diabetic rats

Savi

Bocchi

Mena

et al. 2017

Cardiovasc Diabetol

108

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BackgroundEmerging evidence suggests that specific (poly)phenols may constitute new preventative strategies to counteract cell oxidative stress and myocardial tissue inflammation, which have a key role in the patho-physiology of diabetic cardiomyopathy. In a rat model of early diabetes, we evaluated whether in vivo administration of urolithin A (UA) or urolithin B (UB), the main gut microbiota phenolic metabolites of ellagitannin-rich foods, can reduce diabetes-induced microenvironmental changes in myocardial tissue, preventing cardiac functional impairment.MethodsAdult Wistar rats with streptozotocin-induced type-1 diabetes (n = 29) were studied in comparison with 10 control animals. Diabetic rats were either untreated (n = 9) or subjected to daily i.p. injection of UA (n = 10) or UB (n = 10). After 3 weeks of hyperglycaemia, hemodynamics, cardiomyocyte contractile properties and calcium transients were measured to assess cardiac performance. The myocardial expression of the pro-inflammatory cytokine fractalkine and proteins involved in calcium dynamics (sarcoplasmic reticulum calcium ATPase, phospholamban and phosphorylated phospholamban) were evaluated by immunoblotting. Plasma, urine and tissue distribution of UA, UB and their phase II metabolites were determined.ResultsIn vivo urolithin treatment reduced by approximately 30% the myocardial expression of the pro-inflammatory cytokine fractalkine, preventing the early inflammatory response of cardiac cells to hyperglycaemia. The improvement in myocardial microenvironment had a functional counterpart, as documented by the increase in the maximal rate of ventricular pressure rise compared to diabetic group (+18% and +31% in UA and UB treated rats, respectively), and the parallel reduction in the isovolumic contraction time (−12%). In line with hemodynamic data, both urolithins induced a recovery of cardiomyocyte contractility and calcium dynamics, leading to a higher re-lengthening rate (+21%, on average), lower re-lengthening times (−56%), and a more efficient cytosolic calcium clearing (−32% in tau values). UB treatment also increased the velocity of shortening (+27%). Urolithin metabolites accumulated in the myocardium, with a higher concentration of UB and UB-sulphate, potentially explaining the slightly higher efficacy of UB administration.ConclusionsIn vivo urolithin administration may be able to prevent the initial inflammatory response of myocardial tissue to hyperglycaemia and the negative impact of the altered diabetic milieu on cardiac performance.

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Section: Discussionsupporting

confidence: 87%

In vivo administration of urolithin A and B prevents the occurrence of cardiac dysfunction in streptozotocin-induced diabetic rats

Savi

Bocchi

Mena

et al. 2017

Cardiovasc Diabetol

108

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“…The decreased PPAR-γ is a critical determinant for ox-LDL-induced endothelial dysfunction [24]. Endothelial PPAR-γ is recognized as a potential candidate for vascular protection from atherosclerosis [25].…”

Section: Resultsmentioning

confidence: 99%

Hypaphorine Attenuates Lipopolysaccharide-Induced Endothelial Inflammation via Regulation of TLR4 and PPAR-γ Dependent on PI3K/Akt/mTOR Signal Pathway

Sun

Zhu

Cai

et al. 2017

IJMS

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Endothelial lesion response to injurious stimuli is a necessary step for initiating inflammatory cascades in blood vessels. Hypaphorine (Hy) from different marine sources is shown to exhibit anti-inflammatory properties. However, the potential roles and possible molecular mechanisms of Hy in endothelial inflammation have yet to be fully clarified. We showed that Hy significantly inhibited the positive effects of lipopolysaccharide (LPS) on pro-inflammatory cytokines expressions, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), monocyte chemoattractant protein 1 (MCP-1) and vascular cellular adhesion molecule-1 (VCAM-1), as well as induction of the phosphorylation of Akt and mTOR in HMEC-1 cells. The downregulated peroxisome proliferator-activated receptor γ (PPAR-γ) and upregulated toll-like receptor 4 (TLR4) expressions in LPS-challenged endothelial cells were prevented by Hy. Inhibition of both PI3K and mTOR reversed LPS-stimulated increases in TLR4 expressions and decreases in PPAR-γ levels. Genetic silencing of TLR4 or PPAR-γ agonist pioglitazone obviously abrogated the levels of pro-inflammatory cytokines in LPS-treated HMEC-1 cells. These results suggest that Hy may exert anti-inflammatory actions through the regulation of TLR4 and PPAR-γ dependent on PI3K/Akt/mTOR signal pathways. Hy may be considered as a therapeutic agent that can potentially relieve or ameliorate endothelial inflammation-associated diseases.

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“…The therapeutic effect of urolithin has been widely recognized (36)(37)(38)(39)(40). Urolithin can enhance the anti-inflammatory effects of neutrophils, alleviate the symptoms of inflammation (36) and protect against prostate cancer (37).…”

Section: Discussionmentioning

confidence: 99%

“…Uro-A and uro-B increase cell viability and protect cells, reduce malondialdehyde content and enhance superoxide dismutase activity (38). Uro-A regulates the expression of intercellular adhesion factor-1 via the ERK/peroxisome proliferator activated receptor-γ signaling pathway, which exerts anti-inflammatory effects (39). Uro-A also induces mitophagy, prolongs the lifespan of Caenorhabditis elegans and increases muscle function in rodents (40,41).…”

Section: Discussionmentioning

confidence: 99%

Metabolite identification of gut microflora‑cassia seed interactions using UPLC‑QTOF/MS

et al. 2020

Exp Ther Med

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Cassia seed is the dried ripe seed of Cassia obtusifolia L. or Cassia tora L., which is widely used as a food or traditional Chinese medicine. The aim of the present study was to detect the components and metabolites in the culture of human or rat intestinal microflora suspension with the water decoction of cassia seed in vitro, using an ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry system equipped with a negative ion scan mode. Initially, ellagic acid was identified in the cassia seed decoction. Subsequently, six different metabolites, including urolithin (uro)-A, uro-B, uro-D, uro-M6, uro-M7 and uro-B-glucuronide (glur), were detected after co-culture of the cassia seed decoction with intestinal microflora, but not in the cassia seed decoction alone. Uro-M6, uro-M7, uro-A and uro-B were common metabolites in the culture of human or rat intestinal microflora suspension with the water decoction of cassia seed. However, uro-D was only detected in the culture of rat intestinal microflora suspension with the water decoction of cassia seed, and uro-B-glur was only detected in the culture of human intestinal microflora with the water decoction of cassia seed. The uro and intermediate metabolites were produced by ellagic acid in the cassia seed decoction under the action of the intestinal microflora. The production of metabolites might be related to the abundance and diversity of the intestinal microflora in humans and rats. The present study provided rationale for further pharmacological and clinical studies on the mechanisms of action of cassia seeds.

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Urolithin A attenuates ox‐LDL‐induced endothelial dysfunction partly by modulating microRNA‐27 and ERK/PPAR‐γ pathway

Abstract: UA could alleviate endothelial dysfunction induced by ox-LDL partially through modulating miR-27 expression and ERK/PPAR-γ pathway.

Cited by 47 publications

References 58 publications

In vivo administration of urolithin A and B prevents the occurrence of cardiac dysfunction in streptozotocin-induced diabetic rats

In vivo administration of urolithin A and B prevents the occurrence of cardiac dysfunction in streptozotocin-induced diabetic rats

Hypaphorine Attenuates Lipopolysaccharide-Induced Endothelial Inflammation via Regulation of TLR4 and PPAR-γ Dependent on PI3K/Akt/mTOR Signal Pathway

Metabolite identification of gut microflora‑cassia seed interactions using UPLC‑QTOF/MS

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