Targeted metabolic profiling of pomegranate polyphenols and urolithins in plasma, urine and colon tissues from colorectal cancer patients

Núñez‐Sánchez, María Ángeles; Garcı́a-Villalba, Rocío; Monedero‐Saiz, Tamara; García‐Talavera, Noelia V.; Gómez‐Sánchez, María B.; Sánchez‐Álvarez, Carmen; García‐Albert, Ana M.; Rodríguez‐Gil, Francisco J.; Ruiz‐Marín, Miguel; Pastor-Quirante, Francisco; Martínez‐Díaz, Francisco; Yáñez‐Gascón, María J.; González‐Sarrías, Antonio; Tomás‐Barberán, Francisco A; Espı́n, Juan Carlos

doi:10.1002/mnfr.201300931

Cited by 196 publications

(182 citation statements)

References 38 publications

(73 reference statements)

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“…In most situations, this is difficult to precisely determine, as in vivo metabolic studies are not available for most compounds. Although only a few such studies exist for pomegranate juice (Cerda et al 2003a,b, Mertens-Talcott et al 2006, Nielsen et al 2008, what is clear is that ingestion of 235 ml/day (about 8 ounces) of pomegranate juice results in detectable metabolites in the circulation (Mertens-Talcott et al 2006, Nunez-Sanchez et al 2014. We showed previously that antenatal ingestion of 235 ml/day of pomegranate juice is sufficient to reduce in vivo oxidative stress in the placentas of women who underwent labor .…”

Section: Discussionmentioning

confidence: 95%

Punicalagin promotes autophagy to protect primary human syncytiotrophoblasts from apoptosis

Wang¹,

Chen²,

Longtine³

et al. 2016

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Punicalagin is a prominent polyphenol in pomegranate juice that protects cultured syncytiotrophoblasts from stress-induced apoptosis. Here, we test the hypothesis that punicalagin has this effect by inhibiting the mTOR kinase pathway to enhance autophagic turnover and limit apoptosis in cultured primary human syncytiotrophoblasts. In syncytiotrophoblasts, starvation, rapamycin, or punicalagin all decreased the expression of phosphorylated ribosomal protein S6, a downstream target of the mTOR kinase, and of the autophagy markers, LC3-II and p62. In contrast, in the presence of bafilomycin, an inhibitor of late stages of autophagy and degradation in the autophagolysosome, syncytiotrophoblasts exposed to starvation, rapamycin, or punicalagin all showed increased levels of LC3-II and p62. The number of LC3-II punctae also increased in punicalagin-treated syncytiotrophoblasts exposed to chloroquine, another inhibitor of autophagic degradation, and punicalagin increased the number of lysosomes. The apoptosis-reducing effect of punicalagin was attenuated by inhibition of autophagy using bafilomycin or knockdown of the autophagy related gene, ATG16L1. Collectively, these data support the hypothesis that punicalagin modulates the crosstalk between autophagy and apoptosis to promote survival in cultured syncytiotrophoblasts.

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Section: Discussionmentioning

confidence: 95%

Punicalagin promotes autophagy to protect primary human syncytiotrophoblasts from apoptosis

Wang¹,

Chen²,

Longtine³

et al. 2016

Reproduction

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“…P or HFD ? GT values were reported and expressed as foldbasal (n = 11) *P \ 0.05 versus CTRL, P \ 0.05 versus HFD Eur J Nutr Pomegranate and green tea extracts do not protect mice against HFD-induced obesity In human studies, the typical dose used for pomegranate extracts is about 1 g/day [25][26][27] and between 300 mg and 4 g/day for green tea extracts [28,29], which corresponds to 5-65 mg/kg body weight/day. Considering species differences, this corresponds roughly to 500 mg of extracts/kg body weight/day in mice [30,31].…”

Section: Discussionmentioning

confidence: 99%

Pomegranate and green tea extracts protect against ER stress induced by a high-fat diet in skeletal muscle of mice

et al. 2014

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Purpose We tested the hypothesis that polyphenol-rich extracts can reduce endoplasmic reticulum (ER) stress induced by a high-fat diet (HFD) in skeletal muscle of mice. Methods Mice were randomly assigned to four groups receiving during 20 weeks either a standard chow control (CTRL), or a HFD supplemented, or not, with pomegranate (HFD ? P) or green tea (HFD ? GT) extracts. After the nutritional intervention, mice were killed and gastrocnemius muscles were taken. Proteins and mRNA were measured by Western blot and RT-qPCR, respectively. Results Body weight gain and visceral fat were higher in HFD, HFD ? P and HFD ? GT than in CTRL. The markers of the unfolded protein response BiP, XBP1u, XBP1s and ATF4 were higher only in HFD. In HFD ? P and HFD ? GT, this increase was not observed except for CHOP, which was elevated in all HFD groups. HFD increased also markers of ubiquitin-proteasome pathway, autophagy and oxidative stress, which were kept low in HFD ? P and HFD ? GT groups. Conclusion Our data provide evidence for a protective effect of pomegranate and green tea extracts against ER stress, oxidative stress and protein degradation induced by HFD in skeletal muscle. They give arguments for a usefulness of these natural nutritional compounds to fight against cellular dysfunctions related to fat excess.

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“…However, the main problem associated with the application of some plant-derived compounds is biological instability [13]. Previous studies showed that the incorporation of plant-derived compounds into nanoliposomes could overcome this limitation [14].…”

Section: Discussionmentioning

confidence: 99%

“…It has inhibitory effect on different kinds of cancer cells including prostate and colon cancer cells [11,12]. However, the in vivo instability of punicalagin has restricted its use in biomedical research [13]. Previous studies showed that encapsulation of plant-derived materials in nanocarriers such as nanoliposomes markedly reduced their in vivo instability and increased their effectiveness [14,15].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of telomerase activity and cell growth by free and nanoliposomal forms of punicalagin in human leukemia cell line K562

Ghorbanihaghjo¹,

Faezizadeh²,

Godarzee³

2016

Trop. J. Pharm Res

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Purpose: To prepare punicalagin-loaded nanoliposome and compare its anti-telomerase activity in K562 cell line with that of free punicalagin. Methods: Punicalagin-loaded nanoliposomes were prepared by extrusion method, and the efficiency of punicalagin entrapment was determined by high-performance liquid chromatography (HPLC) method. The anti-proliferation effect of the punicalagin in the free and nanoliposomal forms at various doses (0 -100 µg/mL) and times (0 -72 h) on K562 cell line was investigated using 3-(4,5-dimethylthiazol-2-yl)-

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Targeted metabolic profiling of pomegranate polyphenols and urolithins in plasma, urine and colon tissues from colorectal cancer patients

Abstract: Significant levels of EA derivatives and urolithins are found in human colon tissues from CRC patients after consumption of pomegranate. Further studies are warranted to elucidate their biological activity.

Cited by 196 publications

References 38 publications

Punicalagin promotes autophagy to protect primary human syncytiotrophoblasts from apoptosis

Punicalagin promotes autophagy to protect primary human syncytiotrophoblasts from apoptosis

Pomegranate and green tea extracts protect against ER stress induced by a high-fat diet in skeletal muscle of mice

Inhibition of telomerase activity and cell growth by free and nanoliposomal forms of punicalagin in human leukemia cell line K562

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