Moderate alcohol consumption has been associated with beneficial effects on human health. Specifically, consumption of red wine and beer has shown a J-shape relation with many important diseases. ...While a role of ethanol cannot be excluded, the high content of polyphenols in both beverages has been proposed to contribute to these effects, with beer having the advantage over wine that it is lower in alcohol. In addition to ethanol, beer contains a wide variety of compounds with known medicinal potential such as kaempferol, quercetin, tyrosol and phenolic acids, and it is the main dietary source for the flavones xanthohumol and 8-prenylnaringenin, and bitter acids such as humulones and lupulones. Clinical and pre-clinical evidence for the protective effects of moderate beer consumption against cardiovascular disease and other diseases has been accumulating since the 1990s, and the non-alcoholic compounds of beer likely exert most of the observed beneficial effects. In this review, we summarize and discuss the effects of beer consumption in health and disease as well as the clinical potential of its non-alcoholic compounds which may be promising candidates for new therapies against common chronic diseases.
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•XN-loaded microemulsions based on T80 and SL were prepared using PTPDs.•Both T80-MEs and SL-MEs dramatically increase the solubility and half-life of XN.•The incorporation of SL in ...microemulsions provided XN with better storage stability, solubilization efficiency, antioxidant properties, etc.
Xanthohumol (XN) has numerous compelling physiological activities, but the poor solubility and stability severely limit its utilization. Therefore, a microemulsion (ME) delivery system based on biosurfactant sophorolipids (SLs) was established and its improvement on physicochemical properties of XN was investigated. The results showed that the systems increased the solubility of XN by about 4000 times, and its half-life during storage was extended to over 150 days. Partial replacement of Tween 80 with SL did not greatly affect their ability to form O/W subregions (in the high aqueous phase), but further improved the solubilization efficiency, storage stability, and antioxidant properties of XN. In vitro models revealed the release profile of XN from the systems followed non-Fickian diffusion, and the ME structure markedly strengthened its digestive stability and bioaccessibility. These results indicated that SL-based ME systems had great potential as a green solubilization and delivery method for XN and other hydrophobic drugs.
We used confocal microscopy and spectrofluorescence to characterize the emission spectra in hop flowers, to follow the isomerization processes in different hop preparations, and beers, to compare ...with HPLC extracted samples. Flowers of different hop cultivars produced in three regions of Brazil, were quantitated by HPLC and GC–MS. The fluorescence spectra showed two characteristic emission bands evaluated from different preparations. The isomerization process leads to a gradual decrease in fluorescence intensity as the reaction progresses. This demonstrates the valuable use of confocal microscopy and fluorescence spectroscopy for analysis of the correlation between bitter acid indices with fluorescence intensity and lifetime microscopy. Such techniques can be used directly in the flowers allowing rapid monitoring of the brewing process. Twenty-nine substances were characterized in the essential oils and some cultivars presented quantities of bitter acids and essential oil levels close to those expected for plants after more than three years of cultivation.
•Hop bitter acids were evaluated by HPLC, confocal microscopy and spectrofluorimetry•Confocal microscopy data demonstrate that hop preparations are fluorescent•Intensity of fluorescence is dependent on bitter acid concentration•Isomerization of bitter acids caused a decrease in fluorescence and longevity•Use of these new methods should allow rapid analyses negating the use of solvents
Xanthohumol (XN) is a prenylated flavonoid known for its antioxidant and anti-inflammatory effects and has been studied as an anti-cancer agent. In this study, we aimed at analysing the effect of XN ...on a primary colorectal adenocarcinoma cell line, HT29, on cell viability, inflammatory and antioxidant gene expression, and metabolism. For this purpose, cells were treated with 10 nM and 10 µM XN, and cell viability, H
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production, lipid peroxidation and gene expression of inflammatory, antioxidant, and mitochondrial-related genes, as well as protein levels of metabolic enzymes, were determined. Results showed no significant effects on cell viability and a general decrease in pro-inflammatory, antioxidant and mitochondrial biogenesis gene expression with the lower concentration of XN. Furthermore, glucose and oxidative metabolism enzymes were also reduced. These results suggest that XN treatment, at low doses, could stop the proliferation and progression of HT29 cells by downregulating inflammatory signals and cell metabolism.
Xanthohumol (XN), as an abundant chalcone in hops, has received increasing attention due to its pharmacologic effects. However, poor solubility and bioaccessibility in aqueous solutions have limited ...its application. This work reported a novel carrier to improve the solubility and bioaccessibility of XN by using heat-stable, serpin-like protein Z (PZ) derived from barley malt. In this study, the solubility of XN was increased by 145-fold (vs. free XN in water) using 200 μM PZ as the carrier. Fluorescence results demonstrated that XN interacted with PZ via static quenching process, with binding constant (K a) of 5.70 × 10 4 L/mol at 298 K. PZ as a serine protease inhibitor exhibited excellent in vitro digestive stability that could inhibit trypsin with a low half inhibitory concentration (IC50) of 3.90 ± 0.03 mg/L and showed only 26.54 ± 0.70% degree of hydrolysis after gastrointestinal digestion. Furthermore, the retention ratio of XN was 50.28 ± 1.80% after gastrointestinal digestion, which is 8-fold higher than XN alone, suggesting that PZ remarkably enhanced the bioaccessibility of XN. Molecular dynamics simulation analysis revealed that XN was bound within the hydrophobic pocket of PZ, near the Glu338 residue of PZ, whereas the external active loop of PZ was involved in binding with trypsin. This helped to elucidate the roles of PZ in improving the bioaccessibility of XN that PZ encapsulated XN in its hydrophobic cavity, without influencing its inhibition on trypsin. These findings suggest that PZ may be developed as carriers that protect XN or other hydrophobic bioactive molecules in the gastrointestinal tract.
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•The solubility of xanthohumol (XN) bound with protein Z increased about 145-fold.•Protein Z can form stable complexes with XN mainly via hydrophobic interactions.•Encapsulation of XN in the binding pocket of protein Z improved its bioaccessibility.•Exterior ring of protein Z interacted with trypsin to inhibit protein Z degradation.
Acetaminophen (APAP) is one of the world's popular and safe painkillers, and overdose can cause severe liver damage and even acute liver failure. The effect and mechanism of the xanthohumol on ...acetaminophen-induced hepatotoxicity remains unclear.
The hepatoprotective effects of xanthohumol were studied using APAP-induced HepG2 cells and acute liver injury of mouse, seperately.
In vitro, xanthohumol inhibited H2O2- and acetaminophen-induced cytotoxicity and oxidative stress. Xanthohumol up-regulated the expression of Nrf2. Further mechanistic studies showed that xanthohumol triggered Nrf2 activation via the AMPK/Akt/GSK3β pathway to exert a cytoprotective effect. In vivo, xanthohumol significantly ameliorated acetaminophen-induced mortality, the elevation of ALT and AST, GSH depletion, MDA formation and histopathological changes. Xanthohumol effectively suppressed the phosphorylation and mitochondrial translocation of JNK, mitochondrial translocation of Bax, the activation o cytochrome c, AIF secretion and Caspase-3. In vivo, xanthohumol increased Nrf2 nuclear transcription and AMPK, Akt and GSK3β phosphorylation in vivo. In addition, whether xanthohumol protected against acetaminophen-induced liver injury in Nrf2 knockout mice has not been illustated.
Thus, xanthohumol exerted a hepatoprotective effect by inhibiting oxidative stress and mitochondrial dysfunction through the AMPK/Akt/GSK3β/Nrf2 antioxidant pathway.
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•Xanthohumol, a prenylated flavonoid extracted from Hops (Humulus lupulus), may be effective in treating acetaminophen -induced liver injury.•In vivo and vitro, xanthohumol significantly ameliorated acetaminophen-induced hepatotoxicity.•Xanthohumol protect against acetaminophen-induced hepatotoxicity via Nrf2 activation through the AMPK/Akt/GSK3β pathway.
L. is an essential source of aroma compounds, hop bitter acids, and xanthohumol derivatives mainly exploited as flavourings in beer brewing and with demonstrated potential for the treatment of ...certain diseases. To acquire a comprehensive understanding of the biosynthesis of these compounds, the primary enzymes involved in the three major pathways of hops' phytochemical composition are herein critically summarized. Hops' phytochemical components impart bitterness, aroma, and antioxidant activity to beers. The biosynthesis pathways have been extensively studied and enzymes play essential roles in the processes. Here, we introduced the enzymes involved in the biosynthesis of hop bitter acids, monoterpenes and xanthohumol derivatives, including the branched-chain aminotransferase (BCAT), branched-chain keto-acid dehydrogenase (BCKDH), carboxyl CoA ligase (CCL), valerophenone synthase (VPS), prenyltransferase (PT), 1-deoxyxylulose-5-phosphate synthase (DXS), 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (HDR), Geranyl diphosphate synthase (GPPS), monoterpene synthase enzymes (MTS), cinnamate 4-hydroxylase (C4H), chalcone synthase (CHS_H1), chalcone isomerase (CHI)-like proteins (CHIL), and O-methyltransferase (OMT1). Furthermore, research advancements of each enzyme in terms of reaction conditions, substrate recognition, enzyme structures, and use in engineered microbes are described in depth. Hence, an extensive review of the key enzymes involved in the phytochemical compounds of hops will provide fundamentals for their applications in beer production.
•The correct stereoconfiguration of the bitter acids has been assigned.•Heterogeneous and organocatalysts can be used for the isomerisation of alpha-acids.•Reduction of iso-alpha-acids to ...hexahydro-iso-alpha-acids is feasible in one step.•Alpha-humulene is regioselectively epoxidised.•The chemistry of beta-caryophyllene is governed by its ring strain.
The annual production of hops (Humulus lupulus L.) exceeds 100,000mt and is almost exclusively consumed by the brewing industry. The value of hops is attributed to their characteristic secondary metabolites; these metabolites are precursors which are transformed during the brewing process into important bittering, aromatising and preservative components with rather low efficiency. By selectively transforming these components off-line, both their utilisation efficiency and functionality can be significantly improved. Therefore, the chemical transformations of these secondary metabolites will be considered with special attention to recent advances in the field. The considered components are the hop alpha-acids, hop beta-acids and xanthohumol, which are components unique to hops, and alpha-humulene and beta-caryophyllene, sesquiterpenes which are highly characteristic of hops.
Chalcones (1,3-diaryl-2-propen-1-ones) and their heterocyclic analogues, belong to the flavonoid family, which possess a number of interesting biological properties such as antioxidant, cytotoxic, ...anticancer, antimicrobial, antiprotozoal, antiulcer, antihistaminic and anti-inflammatory activities. Several pure chalcones have been approved for clinical use or tested in humans. Clinical trials have shown that these compounds reached reasonable plasma concentration and are well-tolerated. For this reason they are an object of continuously growing interest amongst the scientists. However, much of the pharmacological potential of chalcones is still not utilized. The purpose of this review is to provide an overview of the pharmacological activity of naturally occurring and synthetic chalcones. This review highlights more recent pharmacological screening of these compounds, their mechanisms of action and relevant structure-activity relationships.
Xanthohumol (XH) is an important prenylated flavonoid that is found within the inflorescence of
L. (Hop plant). XH is an important ingredient in beer and is considered a significant bioactive agent ...due to its diverse medicinal applications, which include anti-inflammatory, antimicrobial, antioxidant, immunomodulatory, antiviral, antifungal, antigenotoxic, antiangiogenic, and antimalarial effects as well as strong anticancer activity towards various types of cancer cells. XH acts as a wide ranging chemopreventive and anticancer agent, and its isomer, 8-prenylnaringenin, is a phytoestrogen with strong estrogenic activity. The present review focuses on the bioactivity of XH on various types of cancers and its pharmacokinetics. In this paper, we first highlight, in brief, the history and use of hops and then the chemistry and structure-activity relationship of XH. Lastly, we focus on its prominent effects and mechanisms of action on various cancers and its possible use in cancer prevention and treatment. Considering the limited number of available reviews on this subject, our goal is to provide a complete and detailed understanding of the anticancer effects of XH against different cancers.
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