Isoxanthohumol, a hop-derived flavonoid, alters the metabolomics profile of mouse feces

Fukizawa, Shinya; Yamashita, Masakazu; Fujisaka, Shiho; Tobe, Kazuyuki; Nonaka, Yasuki; Murayama, Norihito

doi:10.12938/bmfh.2019-045

Cited by 6 publications

(7 citation statements)

References 44 publications

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“…Secondary bile acids are cytotoxic DNA-damaging metabolites converted from primary bile acids by 7-α-dehydroxylase ( 45 ) that interfere with proper metabolism of sugars and lipids, causing lipids to accumulate in muscle tissues, induction of oxidative stress and the inflammatory response, mitochondrial dysfunction, insulin resistance, and damage to skeletal muscle cells, thereby increasing the risk of developing DS ( 46 ). Moreover, xanthohumol, a precursor of IX, has been shown to have anti-obesity effects in animal studies ( 47 ). Therefore, IX might improve glucose and lipid metabolism to a certain extent, thereby improving lipid accumulation in diabetes and reducing the possibility of DS.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics analysis reveals serum biomarkers in patients with diabetic sarcopenia

et al. 2023

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IntroductionDiabetic sarcopenia (DS) is characterized by muscle atrophy, slower nerve conduction, reduced maximum tension generated by skeletal muscle contraction, and slower contraction rate. Hence, DS can cause limb movement degeneration, slow movement, reduced balance, reduced metabolic rate, falls, fractures, etc. Moreover, the relevant early biological metabolites and their pathophysiological mechanism have yet to be characterized.MethodThe current cross-sectional study employed serum metabolomics analysis to screen potential noninvasive biomarkers in patients with diabetic sarcopenia. A total of 280 diabetic patients were enrolled in the study (n = 39 sarcopenia [DS], n = 241 without sarcopenia [DM]). Ten patients were randomly selected from both groups. Non-targeted metabolomic analysis was performed by ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.ResultsA total of 632 differential metabolites were identified, including 82 that were significantly differentially abundant (P < 0.05, VIP > 1, FC > 1.2 or FC < 0.8). Compared with the DM group, the contents of pentadecanoic acid, 5'-methylthioadenosine (5'-MTA), N,N-dimethylarginine (asymmetric dimethylarginine, ADMA), and glutamine in the DS group were significantly increased, while that of isoxanthohumol was decreased.DiscussionBased on receiver operating characteristic curve analysis, pentadecanoic acid, 5'-MTA, ADMA, and glutamine may serve as potential biomarkers of DS. Moreover, ATP-binding cassette (ABC) transporters and the mammalian target of the rapamycin signaling pathway were found to potentially have important regulatory roles in the occurrence and development of DS (P < 0.05). Collectively, the differential metabolites identified in this study provide new insights into the underlying pathophysiology of DS and serve as a basis for therapeutic interventions.

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Section: Discussionmentioning

confidence: 99%

Metabolomics analysis reveals serum biomarkers in patients with diabetic sarcopenia

et al. 2023

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“…The isomerization to IX could affect the host, as IX possesses similar anti‐obesogenic properties as XN, and affects the composition of the IMB. [ 24,33 ] While DXN was found in the feces of both CV and GF mice, the DXN concentration in GF mice was less than half the concentration observed in CV mice. In humans, the enoate reductase (ERED) enzyme of Eubacterium ramulus was previously shown to catalyze the conversion of XN to DXN.…”

Section: Discussionmentioning

confidence: 99%

“…[ 30 ] Furthermore, the protonophore IX affects alpha‐ and beta‐diversity and changes IMB composition. [ 24,25,33,34 ] Given the importance of the IMB in the development of diet‐induced obesity (DIO), and changes in IMB composition observed with XN supplementation, we hypothesize the IMB is required for XN to ameliorate metabolic symptoms associated with DIO.…”

Section: Introductionmentioning

confidence: 99%

Xanthohumol Requires the Intestinal Microbiota to Improve Glucose Metabolism in Diet‐Induced Obese Mice

Logan

Shulzhenko²,

Sharpton

et al. 2021

Molecular Nutrition Food Res

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Scope The polyphenol xanthohumol (XN) improves dysfunctional glucose and lipid metabolism in diet‐induced obesity animal models. Because XN changes intestinal microbiota composition, the study hypothesizes that XN requires the microbiota to mediate its benefits. Methods and Results To test the hypothesis, the study feeds conventional and germ‐free male Swiss Webster mice either a low‐fat diet (LFD, 10% fat derived calories), a high‐fat diet (HFD, 60% fat derived calories), or a high‐fat diet supplemented with XN at 60 mg kg−1 body weight per day (HXN) for 10 weeks, and measure parameters of glucose and lipid metabolism. In conventional mice, the study discovers XN supplementation decreases plasma insulin concentrations and improves Homeostatic Model Assessment of Insulin Resistance (HOMA‐IR). In germ‐free mice, XN supplementation fails to improve these outcomes. Fecal sample 16S rRNA gene sequencing analysis suggests XN supplementation changes microbial composition and dramatically alters the predicted functional capacity of the intestinal microbiota. Furthermore, the intestinal microbiota metabolizes XN into bioactive compounds, including dihydroxanthohumol (DXN), an anti‐obesogenic compound with improved bioavailability. Conclusion XN requires the intestinal microbiota to mediate its benefits, which involves complex diet‐host‐microbiota interactions with changes in both microbial composition and functional capacity. The study results warrant future metagenomic studies which will provide insight into complex microbe‐microbe interactions and diet‐host‐microbiota interactions.

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“…An IXA‐enriched product named Isoxanthoflav (Hopsteiner, Mainburg, Germany) with a purity of IXA over 90% was used for the study and was the same product used in a previous report (Fukizawa, Yamashita, Fujisaka, et al., 2020 ). Quercetin‐3,3′,4′,7‐tetramethyl ether (QTM) was purchased from Extrasynthase (1074, Lyon, France, >90% purity, CAS No.…”

Section: Methodsmentioning

confidence: 99%

“…IXA functions as an anti‐cancer phytochemical by inhibiting the growth and/or proliferation of cultured cells, including ovarian cells (A2780), colon cancer cells (HT‐29 and SW620), and breast cancer cells (MCF‐7) (Bartmańska et al., 2018 ; Miranda et al., 1999 ; Seliger et al., 2019 ). Animal studies demonstrated that IXA prevented fat‐weight gain, affected fecal metabolite components, and suppressed insulin resistance in mice fed a high‐fat diet (Fukizawa, Yamashita, Fujisaka, et al., 2020 ; Fukizawa, Yamashita, Wakabayashi, et al., 2020 ; Yamashita et al., 2020 ). IXA also inhibited the differentiation of 3T3L1 adipocytes and suppressed sterol regulatory element‐binding protein activity in Huh‐7 cells (Inoue et al., 2018 ; Kiyofuji et al., 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Tissue distribution and pharmacokinetics of isoxanthohumol from hops in rodents

Mukai,

Hata

2023

Food Science & Nutrition

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Vegetables and fruits contain prenylflavonoids with biological functions that might improve human health. The prenylflavonoid isoxanthohumol (IXA) and its derivative, 8‐prenylnaringenin (8‐PN), have beneficial activities, including anti‐cancer effects and suppression of insulin resistance. However, their pharmacokinetic profile is unclear. Previous studies suggested flavonoids have low systemic availability and are excreted via the feces. Therefore, this study investigated the tissue distribution dynamics of high‐purity IXA (>90%) from hops administered orally, either singly (50 mg/kg body weight [BW]) or daily for 14 days (30 mg/kg BW), to mice. High‐pressure liquid chromatography demonstrated that IXA was absorbed rapidly after a single administration and reached plasma maximum concentration (Cmax) (3.95 ± 0.81 μmol/L) by 0.5 h. IXA was present at high levels in the liver compared with the kidney, pancreas, lung, skeletal muscle, spleen, thymus, and heart. The highest IXA level after 14 days of IXA ingestion was observed in the liver, followed by the kidney, thymus, spleen, lung, and brain. There was no significant difference in IXA accumulation in tissues between the single and multiple dose groups. Analyses of the livers of rats treated with different concentrations of IXA (112.5–1500 mg/kg BW) once a day for 28 days demonstrated that IXA accumulated dose‐dependently with a correlation coefficient of .813. The accumulation of 8‐PN was dependent on the intake period but not the intake amount of IXA (correlation coefficient −.255). In summary, IXA and 8‐PN were detected in tissues and organs up to 24 h after ingestion, suggesting that orally ingested IXA might have health benefits as a nutraceutical.

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Isoxanthohumol, a hop-derived flavonoid, alters the metabolomics profile of mouse feces

Cited by 6 publications

References 44 publications

Metabolomics analysis reveals serum biomarkers in patients with diabetic sarcopenia

Metabolomics analysis reveals serum biomarkers in patients with diabetic sarcopenia

Xanthohumol Requires the Intestinal Microbiota to Improve Glucose Metabolism in Diet‐Induced Obese Mice

Tissue distribution and pharmacokinetics of isoxanthohumol from hops in rodents

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