Dietary supplement of isohumulones inhibits the formation of aberrant crypt foci with a concomitant decrease in prostaglandin E2 level in rat colon

Applied Bioresearch Center, Kirin Brewery Co., Ltd., Takasaki-shi Gunma, Japan.
Molecular Nutrition & Food Research (Impact Factor: 4.6). 08/2005; 49(8):772-8. DOI: 10.1002/mnfr.200500027
Source: PubMed


Male Fischer 344 rats were subcutaneously injected with azoxymethane (AOM) twice weekly at a dose of 15 mg/kg and were fed with freeze-dried (FD) samples of beer brewed without hops (non-hops beer), beer with hops at 4 times the amount of regular lager beer (x 4-hops beer), and isomerized hop extract (IHE) for the whole experimental period (I/PI) or for the post-initiation period (PI) only. Feeding FD beer samples at a dose of 1% significantly decreased the number of aberrant cryp foci (ACF) in the PI protocol over five weeks.x4-hops beer showed stronger inhibitory effects on the development of the numbers of aberrant crypts per focus and large ACF with four or more crypts than non-hops beer. Feeding IHE to rats at a dose of 0.01% or 0.05% in either the I/PI or PI experiment significantly reduced the numbers of ACF. Prostaglandin E2 (PGE2) levels in colonic mucosa of AOM-treated rats were significantly reduced by feeding of IHE. PGE2 production induced by lipopolysaccharide/interferon-gamma (LPS/IFN-gamma) in RAW264.7 cells was also reduced by treatment with IHE and isohumulone in a dose-dependent manner. These observations suggest that isohumulones show chemopreventive effects on ACF formation in rat colon by inhibiting the production of PGE2.

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    • "In a companion study this same group reported that the administration of isohumulones prevented high fat diet-induced obesity in the C57BL/6N mouse model [21]. Nozawa et al. also reported that dietary supplementation with isohumulones was found to reduce the production of the proinflammatory prostaglandin E 2 in the rat colon suggesting a tissue-specific anti-inflammtory effect [22]. In 2005 Tripp reported the unique antiinflammatory potential and putative mechanism of action of the isohumulones [23] [24]. "
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    ABSTRACT: The lipophilic extracts of the common hops (Humulus lupulus) contain compounds that are readily modified to the family of isohumulones (e.g., iso-alpha acids). The isohumulones have been found to reduce metabolic inflammation and insulin resistance, and positively impact dyslipidemia and obesity. These effects are consistent across studies in multiple cell lines, animal model systems and human intervention trials. Mechanistic work has demonstrated that these isohumulones have a unique pleiotropic mechanism of action which is consistent with their demonstrated safety and range of physiological effects. It is suggested from this extensive body of work that specific isohumulones may be important bioactive agents for the application in medical nutrition therapy in the support of diseases associated with chronic inflammation and insulin resistance.
    PharmaNutrition 04/2015; 21(2). DOI:10.1016/j.phanu.2015.03.001
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    ABSTRACT: th , 2008; Accepted: August 31 st , 2008 Phytochemical analysis and chemopreventive testing of a special "α-/β-acid free" hops extract led to the identification of isohumulones (hops iso-α-acids) as potent inducers of NAD(P)H:quinone reductase (QR) activity. CD values (concentrations required to double the specific activity of QR in Hepa1c1c7 cell culture) were in the range of 1.3 to 10.2 µg/mL, with CD value of trans-isohumulone < cis-isoadhumulone < cis-isocohumulone < cis-isohumulone (+ trans-isoadhumulone). Humulones (hops α-acids) were equally active with CD values of 3.4 to 7.6 µg/mL. However, these activities were accompanied by cytotoxicity. Cohumulinone and humulinone, oxidation products of co- and n-humulone, were inactive. We further identified isohumulones as potent inhibitors of lipopolysaccharide-induced inducible nitric oxide synthase (iNOS) activity in Raw264.7 cell culture, with IC50 values of 5.9 - 18.4 µg/mL. Humulones and humulinones were inactive at concentrations < 20 µg/mL. These results indicate that isohumulones, which are considered as the most abundant class of polyphenols in beer, should by further investigated for chemopreventive efficacy in animal models.
    Natural product communications 01/2008; 3(12). · 0.91 Impact Factor
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