Caffeic acid phenethyl ester reduces the activation of the nuclear factor κB pathway by high-fat diet-induced obesity in mice

Bezerra, Rosângela Maria Neves; Veiga, Lucimara Fernanda; Caetano, Aline Camila; Rosalen, Pedro Luiz; Amaral, Maria Esméria Corezola do; Palanch, Adrianne C.; Alencar, Severino Matias de

doi:10.1016/j.metabol.2012.04.006

Cited by 60 publications

(52 citation statements)

References 34 publications

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“…Recent studies showed that CAPE, a bioactive compound derived from propolis, improves type 2 diabetes (12). To further assess the roles of the intestinal FXR in the effects of CAPE treatment on glucose metabolism, control ( Fxr fl/fl ) mice and intestine-specific Fxr knockout ( Fxr ∆IE ) mice fed an HFD were treated with CAPE.…”

Section: Resultsmentioning

confidence: 99%

An Intestinal Farnesoid X Receptor–Ceramide Signaling Axis Modulates Hepatic Gluconeogenesis in Mice

et al. 2016

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Increasing evidence supports the view that intestinal farnesoid X receptor (FXR) is involved in glucose tolerance and that FXR signaling can be profoundly impacted by the gut microbiota. Selective manipulation of the gut microbiota–FXR signaling axis was reported to significantly impact glucose intolerance, but the precise molecular mechanism remains largely unknown. Here, caffeic acid phenethyl ester (CAPE), an over-the-counter dietary supplement and an inhibitor of bacterial bile salt hydrolase, increased levels of intestinal tauro-β-muricholic acid, which selectively suppresses intestinal FXR signaling. Intestinal FXR inhibition decreased ceramide levels by suppressing expression of genes involved in ceramide synthesis specifically in the intestinal ileum epithelial cells. The lower serum ceramides mediated decreased hepatic mitochondrial acetyl-CoA levels and pyruvate carboxylase (PC) activities and attenuated hepatic gluconeogenesis, independent of body weight change and hepatic insulin signaling in vivo; this was reversed by treatment of mice with ceramides or the FXR agonist GW4064. Ceramides substantially attenuated mitochondrial citrate synthase activities primarily through the induction of endoplasmic reticulum stress, which triggers increased hepatic mitochondrial acetyl-CoA levels and PC activities. These results reveal a mechanism by which the dietary supplement CAPE and intestinal FXR regulates hepatic gluconeogenesis and suggest that inhibiting intestinal FXR is a strategy for treating hyperglycemia.

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Section: Resultsmentioning

confidence: 99%

An Intestinal Farnesoid X Receptor–Ceramide Signaling Axis Modulates Hepatic Gluconeogenesis in Mice

et al. 2016

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“…NF-κB pathway activation is associated with the pathogenesis of chronic inflammatory diseases, including asthma, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease and cancer (59). Furthermore, CAPE demonstrates potential health benefits for the prevention of obesity and associated metabolic disorders and is a potential drug candidate for ischemic stroke treatment due to its inhibition of oxidative stress and inflammation, examples that illustrate how clinically relevant it can be across a wide therapeutic window (49,59). The findings described in this review provide novel insights into the molecular mechanisms underlying the immunomodulatory and anti-inflammatory activities of CAPE.…”

Section: Resultsmentioning

confidence: 99%

“…Several proposed molecular anti-inflammatory mechanisms of CAPE have been suggested by in vivo and in vitro studies. Table I (22,23,30,34,35,(46)(47)(48)(49)(50) summarizes the anti-inflammatory effects of CAPE.…”

Section: Anti-inflammatory Effects Of Capementioning

confidence: 99%

Therapeutic potential of caffeic acid phenethyl ester and its anti-inflammatory and immunomodulatory effects (Review)

Armutçu

Akyol

Üstünsoy

et al. 2015

Experimental and Therapeutic Medicine

141

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Abstract. Caffeic acid phenethyl ester (CAPE), a naturally occurring compound isolated from propolis extract, has been reported to have a number of biological and pharmacological properties, exerting antioxidant, anti-inflammatory, anticarcinogenic, antibacterial and immunomodulatory effects. Recent in vivo and in vitro study findings have provided novel insights into the molecular mechanisms involved in the anti-inflammatory and immunomodulatory activities of this natural compound. CAPE has been reported to have anti-inflammatory properties involving the inhibition of certain enzyme activities, such as xanthine oxidase, cyclooxygenase and nuclear factor-κB (NF-κB) activation. Since inflammation and immune mechanisms play a crucial role in the onset of several inflammatory diseases, the inhibition of NF-κB represents a rationale for the development of novel and safe anti-inflammatory agents. The primary goal of the present review is to highlight the anti-inflammatory and immunomodulatory activities of CAPE, and critically evaluate its potential therapeutic effects. Contents1. Introduction 2. Overview to the inflammatory response 3. Proinflammatory cytokines and signaling pathways 4. Anti-inflammatory effects of CAPE 5. Immunomodulatory effects of CAPE 6. Conclusion IntroductionCaffeic acid phenethyl ester (CAPE) is an important active component of honeybee propolis extract and has been used in traditional medicine for a number of years. CAPE is a polyphenol that contains hydroxyl groups within a catechol ring, the molecular formula of CAPE is C 17 H 16 O 4 (1,2) (Fig. 1). It has been shown that this active component of propolis possesses anti-inflammatory, immunomodulatory, antineoplastic, antioxidant and wound-healing properties (1-4). Inflammation is induced by the release of chemical mediators from damaged tissue and migratory cells. Mediators identified in the inflammatory process include biogenic amines, metabolites of arachidonic acid (eicosanoids), platelet aggregation factors, cytokines [interleukins (ILs) and tumor necrosis factor-α (TNF-α)] and free oxygen radicals. These substances are produced by inflammatory cells, such as polymorphonuclear leukocytes (neutrophils, eosinophils and basophils), endothelial cells, mast cells, macrophages, monocytes and lymphocytes (5,6). CAPE inhibits cytokine and chemokine production, the proliferation of T cells and lymphokine production, and thus suppresses the inflammatory process. Specifically, CAPE is a potent and a specific inhibitor of nuclear factor-κB (NF-κB) activation, and this may provide the molecular basis for its multiple anti-inflammatory and immunomodulatory activities (2,7). The aim of this review is to highlight the anti-inflammatory and immunomodulatory activities of CAPE, focusing on the mechanisms of action (already identified) underlying this activity. Overview to the inflammatory responseInflammation is an immunological response to pathogens and damage that is initiated to protect the body, and contributes Abbreviations: CAPE, caffeic acid phen...

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“…Its protective effects are attributed to its cytoprotective, anti-oxidant, antiproliferative, and anti-inflammatory effects, and it has been shown to inhibit both lipoxygenase activity and lipid peroxidation [3][4][5][6][7][8][9] . CAPE can also inhibit phorbol ester-induced H2O2 production and tumor promotion [10,11] , and it was reported that many CAPE activities were related to transcription factor inhibition of nuclear factor-kappa B (NF-κB) [10,[12][13][14] . Liver fibrosis results from chronic damage to the liver in conjunction with the accumulation of extracellular matrix proteins, which is a characteristic of many chronic liver diseases [15] .…”

Section: Introductionmentioning

confidence: 99%

Caffeic acid phenethyl ester inhibits liver fibrosis in rats

Li¹

2015

WJG

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Caffeic acid phenethyl ester reduces the activation of the nuclear factor κB pathway by high-fat diet-induced obesity in mice

Abstract: Overall, these findings indicate that CAPE exhibited anti-inflammatory activity that partly restores normal metabolism, reduces the molecular changes observed in obesity and insulin resistance, and therefore has a potential as a therapeutic agent in obesity.

Cited by 60 publications

References 34 publications

An Intestinal Farnesoid X Receptor–Ceramide Signaling Axis Modulates Hepatic Gluconeogenesis in Mice

An Intestinal Farnesoid X Receptor–Ceramide Signaling Axis Modulates Hepatic Gluconeogenesis in Mice

Therapeutic potential of caffeic acid phenethyl ester and its anti-inflammatory and immunomodulatory effects (Review)

Caffeic acid phenethyl ester inhibits liver fibrosis in rats

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