Structurally unique isopentenyl flavonoids are extremely low in natural plant species, and their cumbersome chemical pathways, scarcity of donors, and poor stability have severely hindered their ...application scenarios. Xanthohumol (XN), an isopentenyl chalcone, is a unique and abundant herbal efficacy substance in hops (Humulus upulus L.), which is an herb with a variety of clinical benefits. However, 90% of XN is left behind in the production of hop residue, resulting in a waste of natural resources. The poor water solubility and low bioavailability of XN also limit its wide application. Combined biotransformation strategies can greatly enhance the added value of resource materials and become one of the important means for the sustainable utilization of traditional Chinese medicine resources. In this study, an extreme microbial screening strategy for efficient bioconversion of phrenylflavonids is established to achieve Bacillus zanthoxyli GQ8 obtained from brewer's dregs and a non-aqueous biosynthesis system of xanthohumol glycosides (XNG, substrate concentration of 0.5 g/L, conversion rate of 73.2%) is constructed by GQ8. With HT22 cell model of H2O2-induced oxidative damage and BV2 cell model of LPS-induced neuroinflammation, XNG showed little cytotoxicity and exhibited better anti-inflammatory and antioxidant effects compared with the original compound. Our experimental results firstly provide a high-efficiency biotransformation strategy for glycosylation of XN with bacteria and provide a support that prenylflavonoid glycoside derivatives have remarkable biological activity and show better development potential.
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•An extreme microbial screening strategy for efficient bioconversion of xanthohumol is established.•Xanthohumol is converted to xanthohumol glycoside by bacterial for the first time.•The product of Xanthohumol shows significant neuroprotective potential.•Bacillus zanthoxyli GQ8 has substrate hybridity so that realizes the transformation of various flavonoids.
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
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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•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.
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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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•The surface of collagen films in the presence of propanediol and xanthohumol is more hydrophobic, so can have better adhesion to the skin.•In the presence of propandiol and ...xanthohumol the water loss after UV irradiation is smaller than in UV-irradiated collagen films without these additions.•The addition of propandiol and xanthohumol to collagen extracted from the skin of silver carp leads to the modification of surface and mechanical properties of collagen films.•The upper findings help to increase the adhesion of collagen biomaterial to the skin and provide a new solution in protecting biomaterial from increased water loss after the exposition to UV light, which leads to the improvement of collagen biomaterial properties.
Fish skin collagen films are widely used as adhesives in medicine and cosmetology. Ultraviolet (UV) irradiation can be considered as an effective sterilization method for biomaterials, however, it may also lead to material photodegradation. In this work, the influence of xanthohumol and propanediol on the physico-chemical properties of collagen films before and after UV irradiation was studied.
Collagen for this research was extracted from silver carp skin and thin films were fabricated by the solution casting methods.
The structure of films was researched using infrared spectroscopy. The surface properties of films were investigated using Atomic Force Microscopy (AFM) and contact angle measurements. Mechanical properties were measured as well. It was found that the addition of xanthohumol and propanediol modified the roughness of collagen films and their mechanical properties. UV irradiation led to the water loss from the film and modification of the collagen structure.
In the presence of propanediol and xanthohumol the water loss after UV irradiation was smaller than in UV-irradiated collagen films without these additives.
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.
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.
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