Xanthohumol improves cognition in farnesoid X receptor-deficient mice on a high-fat diet.

Xanthohumol (XN) improves cognition of wild-type rodents on a high-fat diet (HFD). Bile acids and ceramide levels in the liver and hippocampus might be linked to these effects. XN modulates activity of the nuclear farnesoid X receptor (FXR; also known as NR1H4), the primary receptor for bile acids.

ApoE isoform-dependent effects of xanthohumol on high fat diet-induced cognitive impairments and hippocampal metabolic pathways.

Consumption of a high fat diet (HFD) is linked to metabolic syndrome and cognitive impairments. This is exacerbated in age-related cognitive decline (ACD) and in individuals with a genetic risk for Alzheimer's disease (AD). Apolipoprotein E (apoE) is involved in cholesterol metabolism.

Computation-Assisted Identification of Bioactive Compounds in Botanical Extracts: A Case Study of Anti-Inflammatory Natural Products from Hops.

The slow pace of discovery of bioactive natural products can be attributed to the difficulty in rapidly identifying them in complex mixtures such as plant extracts. To overcome these hurdles, we explored the utility of two machine learning techniques, i.e.

Phytochemical characterization and bioactivity toward breast cancer cells of unhydrolyzed and acid-hydrolyzed extracts of .

Phytochemicals from the genus, , have been attracting increasing attention due to their potential beneficial effects on human health. species contain various types of phytochemicals such as flavonoids, alkaloids, saponins, terpenoids, coumarins and tannins. In this study, we investigated the phytochemical composition of unhydrolyzed and acid-hydrolyzed extracts of and their bioactivity toward breast cancer MCF-7 cells in vitro.

Xanthohumol Pyrazole Derivative Improves Diet-Induced Obesity and Induces Energy Expenditure in High-Fat Diet-Fed Mice.

The energy intake exceeding energy expenditure (EE) results in a positive energy balance, leading to storage of excess energy and weight gain. Here, we investigate the potential of a newly synthesized compound as an inducer of EE for the management of diet-induced obesity and insulin resistance. Xanthohumol (XN), a prenylated flavonoid from hops, was used as a precursor for the synthesis of a pyrazole derivative tested for its properties on high-fat diet (HFD)-induced metabolic impairments.

Tetrahydroxanthohumol, a xanthohumol derivative, attenuates high-fat diet-induced hepatic steatosis by antagonizing PPARγ.

We previously reported xanthohumol (XN), and its synthetic derivative tetrahydro-XN (TXN), attenuates high-fat diet (HFD)-induced obesity and metabolic syndrome in C57Bl/6J mice. The objective of the current study was to determine the effect of XN and TXN on lipid accumulation in the liver. Non-supplemented mice were unable to adapt their caloric intake to 60% HFD, resulting in obesity and hepatic steatosis; however, TXN reduced weight gain and decreased hepatic steatosis.

Targeting the Liver-Brain Axis with Hop-Derived Flavonoids Improves Lipid Metabolism and Cognitive Performance in Mice.

Scope: Sphingolipids including ceramides are implicated in the pathogenesis of obesity and insulin resistance. Correspondingly, inhibition of pro-inflammatory and neurotoxic ceramide accumulation prevents obesity-mediated insulin resistance and cognitive impairment. Increasing evidence suggests the farnesoid X receptor (FXR) is involved in ceramide metabolism, as bile acid-FXR crosstalk controls ceramide levels along the gut-liver axis.

Germ-Free Swiss Webster Mice on a High-Fat Diet Develop Obesity, Hyperglycemia, and Dyslipidemia.

A calorie-dense diet is a well-established risk factor for obesity and metabolic syndrome (MetS), whereas the role of the intestinal microbiota (IMB) in the development of diet-induced obesity (DIO) is not completely understood. To test the hypothesis that Swiss Webster (Tac:SW) mice can develop characteristics of DIO and MetS in the absence of the IMB, we fed conventional (CV) and germ-free (GF) male Tac:SW mice either a low-fat diet (LFD; 10% fat derived calories) or a high-fat diet (HFD; 60% fat derived calories) for 10 weeks. The HFD increased feed conversion and body weight in GF mice independent of the increase associated with the microbiota in CV mice.

Vitamin C Activates the Folate-Mediated One-Carbon Cycle in C2C12 Myoblasts.

Vitamin C (L-ascorbic acid, AA) is an essential cellular antioxidant and cofactor for several α-ketoglutarate-dependent dioxygenases. As an antioxidant, AA interacts with vitamin E to control oxidative stress. While several reports suggest an interaction of AA with folate (vitamin B9) in animals and humans, little is known about the nature of the interaction and the underlying molecular mechanisms at the cellular level.

Delineation of hypoxia-induced proteome shifts in osteosarcoma cells with different metastatic propensities.

Osteosarcoma (OS) is the most common bone cancer in children and young adults. Solid tumors are characterized by intratumoral hypoxia, and hypoxic cells are associated with the transformation to aggressive phenotype and metastasis. The proteome needed to support an aggressive osteosarcoma cell phenotype remains largely undefined.

Improvements in Metabolic Syndrome by Xanthohumol Derivatives Are Linked to Altered Gut Microbiota and Bile Acid Metabolism.

Scope: Two hydrogenated xanthohumol (XN) derivatives, α,β-dihydro-XN (DXN) and tetrahydro-XN (TXN), improved parameters of metabolic syndrome (MetS), a critical risk factor of cardiovascular disease (CVD) and type 2 diabetes, in a diet-induced obese murine model. It is hypothesized that improvements in obesity and MetS are linked to changes in composition of the gut microbiota, bile acid metabolism, intestinal barrier function, and inflammation.

Methods And Results: To test this hypothesis, 16S rRNA genes were sequenced and bile acids were measured in fecal samples from C57BL/6J mice fed a high-fat diet (HFD) or HFD containing XN, DXN or TXN.

Phytochemical characterization of root bark and its effects on dysfunctional metabolism and cognitive performance in high-fat-fed C57BL/6J mice.

Preparations of the root bark of have long been used in Central and West African traditional medicine to combat fatigue, as a neuro-stimulant in rituals, and for treatment of diabetes. The principal alkaloid of ibogaine, has attracted attention in many countries around the world for providing relief for opioid craving in drug addicts. Using a plant metabolomics approach, we detected five phenolic compounds, including 3--caffeoylquinic acid, and 30 alkaloids, seven of which were previously reported from root bark.

Metabolomics-Driven Elucidation of Cellular Nitrate Tolerance Reveals Ascorbic Acid Prevents Nitroglycerin-Induced Inactivation of Xanthine Oxidase.

Glyceryl trinitrate (GTN) has found widespread use for the treatment of angina pectoris, a pathological condition manifested by chest pain resulting from insufficient blood supply to the heart. Metabolic conversion of GTN, a nitric oxide (NO) pro-drug, into NO induces vasodilation and improves blood flow. Patients develop tolerance to GTN after several weeks of continuous use, limiting the potential for long-term therapy.

Photoprotective Properties of Isothiocyanate and Nitrile Glucosinolate Derivatives From Meadowfoam () Against UVB Irradiation in Human Skin Equivalent.

Exposure to ultraviolet B (UVB) irradiation of the skin leads to numerous dermatological concerns including skin cancer and accelerated aging. Natural product glucosinolate derivatives, like sulforaphane, have been shown to exhibit chemopreventive and photoprotective properties. In this study, we examined meadowfoam () glucosinolate derivatives, 3-methoxybenzyl isothiocyanate (MBITC) and 3-methoxyphenyl acetonitrile (MPACN), for their activity in protecting against the consequences of UV exposure.

Non-estrogenic Xanthohumol Derivatives Mitigate Insulin Resistance and Cognitive Impairment in High-Fat Diet-induced Obese Mice.

Xanthohumol (XN), a prenylated flavonoid from hops, improves dysfunctional glucose and lipid metabolism in animal models of metabolic syndrome (MetS). However, its metabolic transformation into the estrogenic metabolite, 8-prenylnaringenin (8-PN), poses a potential health concern for its use in humans. To address this concern, we evaluated two hydrogenated derivatives, α,β-dihydro-XN (DXN) and tetrahydro-XN (TXN), which showed negligible affinity for estrogen receptors α and β, and which cannot be metabolically converted into 8-PN.

18O-Tracer Metabolomics Reveals Protein Turnover and CDP-Choline Cycle Activity in Differentiating 3T3-L1 Pre-Adipocytes.

The differentiation of precursor cells into mature adipocytes (adipogenesis) has been an area of increased focus, spurred by a rise in obesity rates. Though our understanding of adipogenesis and its regulation at the cellular level is growing, many questions remain, especially regarding the regulation of the metabolome. The 3T3-L1 cell line is the most well characterized cellular model of adipogenesis.

Xanthohumol improves dysfunctional glucose and lipid metabolism in diet-induced obese C57BL/6J mice.

Xanthohumol (XN) is a prenylated flavonoid found in hops (Humulus lupulus) and beer. The dose-dependent effects of XN on glucose and lipid metabolism in a preclinical model of metabolic syndrome were the focus of our study. Forty-eight male C57BL/6J mice, 9 weeks of age, were randomly divided into three XN dose groups of 16 animals.

A metabolomics-driven elucidation of the anti-obesity mechanisms of xanthohumol.

Mild, mitochondrial uncoupling increases energy expenditure and can reduce the generation of reactive oxygen species (ROS). Activation of cellular, adaptive stress response pathways can result in an enhanced capacity to reduce oxidative damage. Together, these strategies target energy imbalance and oxidative stress, both underlying factors of obesity and related conditions such as type 2 diabetes.

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

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 4 week old Zucker fa/fa rats, a rodent model of obesity. Rats received daily oral doses of xanthohumol at 0, 1.

Vitamin C deficiency activates the purine nucleotide cycle in zebrafish.

Vitamin C (ascorbic acid, AA) is a cofactor for many important enzymatic reactions and a powerful antioxidant. AA provides protection against oxidative stress by acting as a scavenger of reactive oxygen species, either directly or indirectly by recycling of the lipid-soluble antioxidant, α-tocopherol (vitamin E). Only a few species, including humans, guinea pigs, and zebrafish, cannot synthesize AA.

Pharmacokinetics of xanthohumol and metabolites in rats after oral and intravenous administration.

Scope: Xanthohumol (XN), a dietary flavonoid found in hops, may have health-protective actions against cardiovascular disease and type 2 diabetes. Yet, there are limited data on the pharmacokinetics (PK) of XN. This study provides PK parameters for XN and its major metabolites in rats.

Formation of a vitamin C conjugate of acrolein and its paraoxonase-mediated conversion into 5,6,7,8-tetrahydroxy-4-oxooctanal.

Vitamin C (ascorbic acid) has been reported to participate in Michael addition reactions in vitro to form vitamin C conjugates with alpha,beta-unsaturated aldehydes, such as acrolein. This study shows evidence for the formation and metabolism of the vitamin C conjugate of acrolein (AscACR) in cultured human monocytic THP-1 cells exposed to acrolein diacetate. By using (18)O and (13)C labeling in combination with liquid chromatography-tandem mass spectrometry, AscACR was shown to undergo hydrolytic conversion of the ascorbyl lactone into an intermediate carboxylic acid.

Xanthohumol and related prenylated flavonoids inhibit inflammatory cytokine production in LPS-activated THP-1 monocytes: structure-activity relationships and in silico binding to myeloid differentiation protein-2 (MD-2).

Xanthohumol (XN) is a prenylated chalcone-type flavonoid found in hops and beer. Our objective of this study was to determine the anti-inflammatory activities of XN, isoxanthohumol (IX), and 15 related prenylated chalcones and flavanones, as well as their structure-activity relationships. The anti-inflammatory activities of the flavonoids were measured by their ability to inhibit lipopolysaccharide (LPS)-induced cytokine production in human monocytic THP-1 cells.