Xanthohumol lowers body weight and fasting plasma glucose in obese male Zucker fa/fa rats

College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA.
Phytochemistry (Impact Factor: 2.55). 05/2012; 91. DOI: 10.1016/j.phytochem.2012.04.018
Source: PubMed


Obesity contributes to increased risk for several chronic diseases including cardiovascular disease and type 2 diabetes. Xanthohumol, a prenylated flavonoid from hops (Humulus lupulus), was tested for efficacy on biomarkers of metabolic syndrome in 4week old Zucker fa/fa rats, a rodent model of obesity. Rats received daily oral doses of xanthohumol at 0, 1.86, 5.64, and 16.9mg/kg BW for 6weeks. All rats were maintained on a high fat (60% kcal) AIN-93G diet for 3weeks to induce severe obesity followed by a normal AIN-93G (15% kcal fat) diet for the last 3weeks of the study. Weekly food intake and body weight were recorded. Plasma cholesterol, glucose, insulin, triglyceride, and monocyte chemoattractant protein-1 (MCP-1) levels were assessed using commercial assay kits. Plasma and liver tissue levels of XN and its metabolites were determined by liquid-chromatography tandem mass spectrometry. Plasma and liver tissue levels of xanthohumol were similar between low and medium dose groups and significantly (p<0.05) elevated in the highest dose group. There was a dose-dependent effect on body weight and plasma glucose levels. The highest dose group (n=6) had significantly lower plasma glucose levels compared to the control group (n=6) in male but not female rats. There was also a significant decrease in body weight for male rats in the highest dose group (16.9mg/kg BW) compared to rats that received no xanthohumol, which was also not seen for female rats. Plasma cholesterol, insulin, triglycerides, and MCP-1 as well as food intake were not affected by treatment. The findings suggest that xanthohumol has beneficial effects on markers of metabolic syndrome.

22 Reads
  • Source
    • " hepatoprotective effects by its antioxidant properties and inhibition of lipid peroxidation and degradation of antioxidant enzymes that are induced by CCl 4 intoxication Pinto et al . , 2012 Metabolic syndrome in 4 week old Zucker fa / fa rats XN has beneficial effects on markers of metabolic syndrome such as body weight and plasma glucose levels Legette et al . , 2013 Amino - 3 - methyl - imidazo [ 4 , 5 - f ] quinoline - induced preneoplastic foci formation in rat livers XN protects against DNA damage and cancer Pinto et al . , 2012 IR - induced hepatic injury in rats XN reduced reactive oxygen species formation and NF - κB activity in vitro and lipid peroxidation was attenuated , while Bcl - X expr"
    [Show abstract] [Hide abstract]
    ABSTRACT: Xanthohumol is the principal prenylated flavonoid of the female inflorescences of the hop plant. In recent years, various beneficial xanthohumol effects including anti-inflammatory, antioxidant, hypoglycemic activities, and anticancer effects have been revealed. This review summarizes present studies indicating that xanthohumol also inhibits several critical pathophysiological steps during the development and course of chronic liver disease, including the activation and pro-fibrogenic genotype of hepatic stellate cells. Also the various mechanism of action and molecular targets of the beneficial xanthohumol effects will be described. Furthermore, the potential use of xanthohumol or a xanthohumol-enriched hop extract as therapeutic agent to combat the progression of chronic liver disease will be discussed. It is notable that in addition to its hepatoprotective effects, xanthohumol also holds promise as a therapeutic agent for treating obesity, dysregulation of glucose metabolism and other components of the metabolic syndrome including hepatic steatosis. Thus, therapeutic xanthohumol application appears as a promising strategy, particularly in obese patients, to inhibit the development as well as the progression of non-alcoholic fatty liver disease.
    Frontiers in Physiology 05/2015; 6. DOI:10.3389/fphys.2015.00140 · 3.53 Impact Factor
    • "The prenylflavonoids xanthohumol (XN), isoxanthohumol (IX), 8-prenylnaringenin (8–PN), 6-prenylnaringenin (6-PN), and 6,8-diprenylnaringenin (Fig. 1) are found in the hop plant (Humulus lupulus L.), specifically its female inflorescences [1] [2], which are well known as an essential ingredient used in beer brewing. XN, the principal prenylflavonoid present in hop extracts [1] [2], has been reported to exhibit anti-cancer, anti-HIV, anti-obesity, and anti-malaria activity [3] [4] [5] [6] [7]. IX is found at higher concentrations (0.04–3.44 mg/L) than other prenylflavonoids in beer due to its derivation from XN in the brewing process [1] [8]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: ScopeHops (Humulus lupulus L.) produce unique prenylflavonoids that exhibit interesting bioactivities. This study investigates the interactions between selected prenylflavonoids and breast cancer resistance protein (BCRP/ABCG2), an efflux transporter important for xenobiotic bioavailability and multidrug resistance (MDR).Methods and resultsABCG2-inhibitory activity of xanthohumol (XN), isoxanthohumol (IX), 6-prenylnaringenin (6-PN), 8-prenylnaringenin (8-PN), and 6,8-diprenylnarigenin (6,8-diPN) was evaluated using mitoxantrone accumulation and vesicular transport assays. XN, IX, and 8-PN were tested for a substrate-type relationship with ABCG2 using ATPase and bidirectional transport assays. The prenylflavonoids exhibited significant ABCG2-inhibitory activities in mitoxantrone accumulation and vesicular transport assays. In the ATPase assay, XN, IX, and 8-PN inhibited baseline and sulfasalazine-stimulated ATPase activities with IC50 of 2.16–27.0 μM. IX and 8-PNalso displayed bell-shaped activation curves in Ko143-suppressed membranes, indicating a substrate-type relationship. For IX, efflux ratios of 1.25±0.21 and 9.18±0.56 were observed in wild-type and ABCG2-overexpressing MDCKII cell monolayers, respectively. The latter was reduced to 1.25±0.15 in the presence of the ABCG2-specific inhibitor Ko143, demonstrating an ABCG2-mediated efflux of IX. Additionally, evidence was shown for the involvement of ABCG2 in the efflux of 8-PN and/or its sulfate conjugate.Conclusion Prenylflavonoids are potent inhibitors of ABCG2 and therefore implicated in ABCG2-mediated food/herb-drug interactions and MDR. ABCG2-mediated efflux of prenylflavonoids may represent one mechanism that regulates prenylflavonoid bioavailability.This article is protected by copyright. All rights reserved
    Molecular Nutrition & Food Research 11/2014; 58(11). DOI:10.1002/mnfr.201400288 · 4.60 Impact Factor
  • Source
    • "In 3T3-L1 adipocytes, Yang et al. reported reduced lipid content and decreased adipocyte marker proteins after incubation with XN [9]. XN also lowers body weight and fasting plasma glucose in obese male Zucker fa/fa rats [10]. Decreased production of the proinflammatory cytokines IL-1 beta, inducible nitric oxide synthase [11], and IL-12 [12] in LPS-activated macrophages, and reduced monocyte chemoattractant protein 1 (MCP-1) and tumor necrosis factor alpha concentrations were observed after XN treatment in mouse macrophages and human monocytes [13]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: ScopeXanthohumol (XN), a prenylated antioxidative and anti-inflammatory chalcone from hops, exhibits positive effects on lipid and glucose metabolism. Based on its favorable biological properties, we investigated whether XN attenuates atherosclerosis in western-type diet-fed apolipoprotein-E-deficient (ApoE(-/-)) mice. Methods and resultsXN supplementation markedly reduced plasma cholesterol concentrations, decreased atherosclerotic lesion area, and attenuated plasma concentrations of the proinflammatory cytokine monocyte chemoattractant protein 1. Decreased hepatic triglyceride and cholesterol content, activation of AMP-activated protein kinase, phosphorylation and inactivation of acetyl-CoA carboxylase, and reduced expression levels of mature sterol regulatory element-binding protein (SREBP)-2 and SREBP-1c mRNA indicate reduced lipogenesis in the liver of XN-fed ApoE(-/-) mice. Concomitant induction of hepatic mRNA expression of carnitine palmitoyltransferase-1a in ApoE(-/-) mice-administered XN suggests increased fatty acid beta-oxidation. Fecal cholesterol concentrations were also markedly increased in XN-fed ApoE(-/-) mice compared with mice fed western-type diet alone. Conclusion The atheroprotective effects of XN might be attributed to combined beneficial effects on plasma cholesterol and monocyte chemoattractant protein 1 concentrations and hepatic lipid metabolism via activation of AMP-activated protein kinase.
    Molecular Nutrition & Food Research 05/2013; 57(10). DOI:10.1002/mnfr.201200794 · 4.60 Impact Factor
Show more