Cisplatin is a chemotherapeutic agent that widely used in the treatment of cancer. However, cisplatin has been reported to induce nephrotoxicity by directly inducing inflammatory response and ...oxidative stress. In this study, we aimed to investigate the protective effects and mechanism of xanthohumol on cisplatin-induced nephrotoxicity. The model of nephrotoxicity was induced by intraperitoneal injection of cisplatin and xanthohumol was given intraperitoneally for three consecutive days. The results showed that xanthohumol significantly attenuated kidney histological changes and serum creatinine and BUN production. The levels of TNF-α, IL-1ß and IL-6 in kidney tissues were suppressed by xanthohumol. The levels of malondialdehyde (MDA) and ROS were suppressed by treatment of xanthohumol. The activities of glutathione (GSH) and superoxide dismutase (SOD) decreased by cisplatin were reversed by xanthohumol. Furthermore, the expression of TLR4 and the activation of NF-κB induced by cisplatin were significantly inhibited by xanthohumol. The expression of Nrf2 and HO-1 were dose-dependently up-regulated by the treatment of xanthohumol. In conclusion, xanthohumol protects against cisplatin-induced nephrotoxicity by ameliorating inflammatory and oxidative responses.
•Xanthohumol attenuates kidney histological changes and serum creatinine and BUN production.•Xanthohumol inhibits cisplatin-induced TNF-α, IL-1ß and IL-6 production in kidney tissues.•Xanthohumol inhibits MDA content and reverses the activities of GSH and SOD decreased by cisplatin.•Xanthohumol inhibits cisplatin-induced NF-κB activation and increases the expression of Nrf2 and HO-1.
Scope
Prenylated chalcones and flavonoids are found in many plants and are believed to have beneficial effects on health when consumed. Xanthohumol is present in beer and likely the most consumed ...prenylated chalcone, but poorly absorbed and rapidly metabolized and excreted, thus limiting its bioavailability. Micellar formulations of phytochemicals have been shown to improve bioavailability.
Methods and results
In a randomized, double‐blind, crossover trial with five healthy (three males and two females) volunteers, a single dose of 43 mg was orally administered as a native or micellar formulation. The major human xanthohumol metabolites are quantified in plasma. Unmetabolized free xanthohumol makes 1% or less of total plasma xanthohumol. The area under the plasma concentration–time curve of xanthohumol‐7‐O‐glucuronide following the ingestion of the micellular formulation is 5‐fold higher and its maximum plasma concentration is more than 20‐fold higher compared to native xanthohumol.
Conclusion
Metabolism of orally ingested xanthohumol is complex and efficiently converts the parent compound to predominantly glucuronic acid and to a lesser extent sulfate conjugates. The oral bioavailability of micellar xanthohumol is superior to native xanthohumol, making it a useful delivery form for future human trials.
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•The use of choline chloride-based DESs allows extraction of xanthohumol from spent hops.•Xanthohumol–rich precipitates are obtained by adding water (antisolvent) to the DES ...extract.•The highest xanthohumol extraction yield was obtained using a DES composed of choline chloride and propylene glycol.•Optimization of the extraction conditions improved the xanthohumol extraction efficiency 3-fold.•DES could be recovered and reused at least three times without compromising the xanthohumol extraction yield.
Spent hops (SH) are a rich source of the prenylated chalcone, xanthohumol (XN), which has a broad spectrum of biological activity. In this study, four choline chloride-based deep eutectic solvents (DESs), which contained glycerol, ethylene glycol, propylene glycol, or lactic acid as a hydrogen bond donor, were tested for the extraction of XN from SH. XN-rich precipitates were obtained by the addition of water (as an antisolvent) to the DES extracts. To determine the XN contents, the precipitates were extracted with methanol and then analyzed by HPLC. The highest XN extraction yield (2.30 mg/g SH) was obtained using a DES composed of choline chloride and propylene glycol (1:2 mol/mol) with 5 wt% water, 1:50 SH/DES (w/w), and 3:1 antisolvent/DES (v/w) at 60 °C for 1 h. This DES could be recovered and reused at least three times without significantly decreasing the XN extraction yield. Our results therefore demonstrated that DESs can be considered green, efficient, and promising solvents for the extraction of XN from SH. Moreover, the proposed simple DES-based method appears to be an effective alternative to conventional XN extraction methods.
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•Environmentally-friendly vapochromic PLA nanofibers (150–450 nm) were developed.•Xanthohumol biomolecule from Humulus lupulus L. was integrated into PLA nanofibers.•Nanoparticles ...(13–27 nm) were created from xanthohumol and aluminum complex.•Blue colorimetric shift from yellow (465 nm) to colorless (315 nm) against ammonia.•Real-time detection of NH3(aq) was achieved with a detection limit of 10–450 mg/L.
Ammonia is a significant industrial gaseous agent that is colorless. However, long exposure to ammonia gas can cause organ damages or even death. This study describes the preparation of a solid-state vapochromic sensor for gaseous and aqueous ammonia using eco-friendly smart colorimetric polylactic acid nanofibers. Xanthohumol (XMOL) is a natural spectroscopic probe that can be found in the common hop (Humulus lupulus L.) plant. Nanoparticles of mordant/xanthohumol (M/XMOL) coordinated complex were synthesized by immobilizing the xanthohumol direct dyestuff into polylactic acid nanofibers in the presence of a mordant (potassium aluminum sulfate). Xanthohumol can be described as an appropriate sensor for gaseous and aqueous ammonia due to its tiny molecular size and high water-solubility. Both of CIE Lab color parameters and absorbance spectra were used to inspect the color shift of the xanthohumol-finished polylactic acid nanofibers from yellow to colorless upon exposure to ammonia. This could be attributed to the intramolecular charge transfer caused by molecular switching of xanthohumol. In a fraction of second, the polylactic acid nanofibrous fabric showed a colorimetric change with a detection limit of 10–450 mg/L. The absorption spectra of the xanthohumol probe exhibited hypsochromic shift with a wavelength change from 465 nm to 315 nm (isosbestic point of 370 nm) in response to an aqueous solution of ammonia. Transmission electron microscopic (TEM) images showed that M/XMOL particles were 13–27 nm in diameter, whereas scanning electron microscopic (TEM) images demonstrated that the polylactic acid nanofibers were 150–450 nm in diameter. We observed no significant differences in air-permeability and bending-length of the nanofibrous fabric after immobilization of M/XMOL into polylactic acid nanofibers. In addition, the colorfastness properties of the treated polylactic acid nanofibers were investigated.
It has been observed that many phytochemicals, frequently present in foods or beverages, show potent chemopreventive or therapeutic properties that selectively affect cancer cells. Numerous studies ...have demonstrated the anticancer activity of xanthohumol (Xn), a prenylated flavonoid isolated from hops (
L.), with a concentration up to 0.96 mg/L in beer. This review aims to summarize the existing studies focusing on the anticancer activity of Xn and its effects on key signaling molecules. Furthermore, the limitations of current studies and challenges for the clinical use of Xn are discussed.
Flavonoids are plant bioactive compounds of great interest in nutrition and pharmacology, due to their remarkable properties as antioxidant, anti-inflammatory, antibacterial, antifungal and antitumor ...drugs. More than 5000 different flavonoids exist in nature, with a huge structural diversity and a plethora of interesting pharmacological properties. In this work, five flavonoids were tested for their potential use as antitumor drugs against three CRC cell lines (HCT116, HT-29 and T84). These cell lines represent three different stages of this tumor, one of which is metastatic. Xanthohumol showed the best antitumor activity on the three cancer cell lines, even better than that of the clinical drug 5-fluorouracil (5-FU), although no synergistic effect was observed in the combination therapy with this drug. On the other hand, apigenin and luteolin displayed slightly lower antitumor activities on these cancer cell lines but showed a synergistic effect in combination with 5-FU in the case of HTC116, which is of potential clinical interest. Furthermore, a literature review highlighted that these flavonoids show very interesting palliative effects on clinical symptoms such as diarrhea, mucositis, neuropathic pain and others often associated with the chemotherapy treatment of CRC. Flavonoids could provide a double effect for the combination treatment, potentiating the antitumor effect of 5-FU, and simultaneously, preventing important side effects of 5-FU chemotherapy.
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•Five plant flavonoids have been tested for their potential as antitumor drugs against human colorectal cancer (CRC) cell lines.•NApigenin and luteolin (and less so naringenin and eriodictyol) showed interesting antitumor activities in vitro.•Xanthohumol displayed the greatest antiproliferative activity, even higher than the clinically used drug 5-fluorouracil.•All these antitumor flavonoids also exert very interesting palliative/preventive effects on clinical symptoms associated to CRC treatment.
Xanthohumol (XN), a prenylated chalcone isolated from the hop plant, has been reported to exhibit multiple biological functions including anti-inflammation. However, the pharmacological function of ...XN on colitis remains unknown. In this study, we investigated the anti-inflammatory effect of synthesized XN and molecular mechanism on dextran sulfate sodium (DSS)-induced experimental colitis. XN attenuated the colitis symptoms along with the prevention of colonic lesions after DSS challenge. XN inhibited the production of pro-inflammatory cytokines, oxidative stress and cyclooxygenase-2 expression in DSS-treated mice. Moreover, XN inhibited the phosphorylation of IκBα, the nuclear translocation of NF-κB subunits and the transcriptional activity of NF-κB
and
. In contrast to XN, isoXN showed much less effects on the kinase activity of IKKβ and IκBα phosphorylation induced by XN in this study, suggesting that an electrophilic carbon center present in XN is critical for the anti-inflammation in colitis, especially inhibition of IKKβ/NF-κB signaling pathway. Consistently, our docking analysis revealed that XN could bind to the active site, presumably at the Cys99 of IKKβ. Taken together, these findings demonstrate a new function of XN to inhibit IKKβ/NF-κB signaling, suggesting XN could be the potential therapeutic agent for the prevention of colitis.
•Bound phenolics are released during malting, leading to an increase of free phenolics.•Wort phenolics content increases during mashing and hopping stages.•Wort boiling and brewing cold stages are ...responsible for significant phenolic losses.•Dry-hopping is a good strategy to improve phenolic profile and content in beer.•Black beers tend to exhibit up to 3-fold higher phenolic levels.
This review provides an overview on the influence of malting and brewing on the overall phenolic content of barley malt and beer. Beer phenolics are mainly originated from barley malt and can be found in free and bound forms, in concentrations up to 50% lower comparing to sweet wort. The use of roasted malts, in combination with proper milling and high mashing temperatures at low pH can lead to a release of bound phenolic forms and increased extraction. New technological strategies such as special yeasts, manipulation of enzymatic activity and dry-hopping may be relevant to improve the phenolic profile of beer and attain phenolic levels with benefits both for beer stability and consumer’s health. As the content of free ferulic acid in beer only accounts up to approximately 15% of total content, further studies should put emphasis on its bound forms in different beer styles and non-alcoholic beers.
Flavonoids and chalcones are known for their manifold biological activities, of which many affect the central nervous system. Pyranochalcones were recently shown to have a great neurogenic potential, ...which is partly due to a specific structural motif-the pyran ring. Accordingly, we questioned if other flavonoid backbones with a pyran ring as structural moiety would also show neurogenic potential. Different semi-synthetic approaches starting with the prenylated chalcone xanthohumol, isolated from hops, led to pyranoflavanoids with different backbones. We identified the chalcone backbone as the most active backbone with pyran ring using a reporter gene assay based on the promoter activity of doublecortin, an early neuronal marker. Pyranochalcones therefore appear to be promising compounds for further development as a treatment strategy for neurodegenerative diseases.
Hop has been attracting scientific attention due to its favorable bioactivity properties. It is thus desirable to relate these properties to the specific hop compounds and extract these compounds in ...highly purified form in order to enhance the effect. The aim of the present study is the isolation of a sufficient amount of the highly purified prenylated minor hop compound xanthohumol C (XNC) for characterizing its bioactivity. Two strategies for the production of XNC were evaluated. The first strategy involved a capture of natural XNC from a xanthohumol (XN)-enriched hop extract (XF) by countercurrent chromatography. In the second approach, a one-step semi-synthesis of XNC was performed starting from XN, which had previously been separated from a natural XN-enriched hop extract. Both methods delivered XNC in sufficient amount and purity (>95%, HPLC), whereas the second strategy was preferable in terms of purity (>99%, HPLC) as well as productivity and solvent consumption. The methods were validated by identifying and quantifying XNC using LC-MS, LC-MS/MS and 1H NMR analysis. The XNC obtained in this way was supplied to several bacterial, yeast and fungal cultures in order to evaluate its antimicrobial effects. For comparison, microorganisms were also treated with the natural XN-enriched hop extract, as well as the prenylated hop compound XN. While still reducing cell proliferation, XNC was found to be less effective than both XF and XN for all studied bacteria and yeasts. Furthermore, for Bacillus subtilis, a strongly pH-dependent minimal inhibition concentration was observed for all three bioactive compounds, lowest at a pH of 5 and highest at a pH of 7.
•Hop extract xanthohumol C capture and enrichment with countercurrent chromatography.•One-step semi-synthesis from xanthohumol to xanthohumol C.•Purification of xantohumol C with countercurrent chromatography.•>99% pure xanthohumol C was obtained.•pH-dependent bioactivity of hop chalcones for gram positive bacteria.
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