Pomegranate Juice and Pomegranate Extract Do Not Impair Oral Clearance of Flurbiprofen in Human Volunteers: Divergence From In Vitro Results

Hanley, Michael; Massé, G; Harmatz, Jerold S.; Court, Michael H.; Greenblatt, David J.

doi:10.1038/clpt.2012.170

Cited by 26 publications

(12 citation statements)

References 47 publications

(67 reference statements)

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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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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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“…The clinical interaction potential for mechanismbased inhibitors is higher than that for reversible inhibitors, because restoration of P450 activity is dependent on de novo protein synthesis rather than removal of the perpetrator compound(s) (Watanabe et al, 2007). For example, MBI has been hypothesized as the only means by which fruit juices can elicit clinically significant interactions with CYP3A substrates (Hanley et al, 2012). Whereas the maximum rates of rCYP3A4 inactivation by silybin A and silybin B were roughly half those reported for a major mechanism-based inhibitor in grapefruit juice, DHB (;0.20 versus 0.41 min 21 ) (Paine et al, 2004), the K I s for silybin A and silybin B were ;100 times greater than those for DHB (;100 versus 1.1 mM).…”

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confidence: 99%

A Systematic Approach to Evaluate Herb-Drug Interaction Mechanisms: Investigation of Milk Thistle Extracts and Eight Isolated Constituents as CYP3A Inhibitors

Brantley

Graf

Oberlies

et al. 2013

Drug Metabolism and Disposition

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Despite increasing recognition of potential untoward interactions between herbal products and conventional medications, a standard system for prospective assessment of these interactions remains elusive. This information gap was addressed by evaluating the drug interaction liability of the model herbal product milk thistle (Silybum marianum) with the CYP3A probe substrate midazolam. The inhibitory effects of commercially available milk thistle extracts and isolated constituents on midazolam 19-hydroxylation were screened using human liver and intestinal microsomes. Relative to vehicle, the extract silymarin and constituents silybin A, isosilybin A, isosilybin B, and silychristin at 100 mM demonstrated >50% inhibition of CYP3A activity with at least one microsomal preparation, prompting IC 50 determination. The IC 50 s for isosilybin B and silychristin were ∼60 and 90 mM, respectively, whereas those for the remaining constituents were >100 mM. Extracts and constituents that contained the 1,4-dioxane moiety demonstrated a >1.5-fold shift in IC 50 when tested as potential mechanism-based inhibitors. The semipurified extract, silibinin, and the two associated constituents (silybin A and silybin B) demonstrated mechanism-based inhibition of recombinant CYP3A4 (K I , ∼100 mM; k inact , ∼0.20 min 21) but not microsomal CYP3A activity. The maximum predicted increases in midazolam area under the curve using the static mechanistic equation and recombinant CYP3A4 data were 1.75-fold, which may necessitate clinical assessment. Evaluation of the interaction liability of single herbal product constituents, in addition to commercially available extracts, will enable elucidation of mechanisms underlying potential clinically significant herb-drug interactions. Application of this framework to other herbal products would permit predictions of herb-drug interactions and assist in prioritizing clinical evaluation.

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“…Also, PJ has been shown to inhibit cytochrome P450 3A (CYP3A), an enzyme involved in the regulation of blood vessel tone. However, unlike grapefruit juice, pomegranate juice has not been shown to inhibit drug clearance in humans by suppression of CYP3A [35] or CYP2C9 [36]. Moreover, multiple studies have shown that PJ also has anticancer [27, 37] and antimicrobial properties [38].…”

Section: Resultsmentioning

confidence: 99%

Pomegranate Supplementation Protects against Memory Dysfunction after Heart Surgery: A Pilot Study

Ropacki

Patel

Hartman

2013

Evidence-Based Complementary and Alternative Medicine

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Memory dysfunction is a common complaint following heart surgery and may be related to a diffuse ischemic state induced by microemboli dislodged during the procedure. Ischemia can induce damage by a number of mechanisms, including oxidative stress. Because pomegranates contain a variety of polyphenols with antioxidant and other potentially beneficial effects, we tested whether supplementation with a pomegranate extract before and after heart surgery could protect against postoperative cognitive dysfunction. Patients undergoing elective coronary artery bypass graft and/or valve surgery were given either 2 g of pomegranate extract (in 2 POMx pills) or placebo (pills containing no pomegranate ingredients) per day from one week before surgery to 6 weeks after surgery. The patients were also administered a battery of neuropsychological tests to assess memory function at 1 week before surgery (baseline), 2 weeks after surgery, and 6 weeks after surgery. The placebo group had significant deficits in postsurgery memory retention, and the pomegranate treatment not only protected against this effect, but also actually improved memory retention performance for up to 6 weeks after surgery as compared to presurgery baseline performance.

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Pomegranate Juice and Pomegranate Extract Do Not Impair Oral Clearance of Flurbiprofen in Human Volunteers: Divergence From In Vitro Results

Cited by 26 publications

References 47 publications

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

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

A Systematic Approach to Evaluate Herb-Drug Interaction Mechanisms: Investigation of Milk Thistle Extracts and Eight Isolated Constituents as CYP3A Inhibitors

Pomegranate Supplementation Protects against Memory Dysfunction after Heart Surgery: A Pilot Study

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