The prevalence of various hepatic diseases increases dramatically worldwide and regarded as a serious health problem. Sirtuins are one of the main strategic controllers of different cellular ...processes, including cell cycle, mitochondrial biogenesis, insulin secretion, redox balance, inflammation, and apoptosis. SIRT1 is the most prominent and broadly studied member of sirtuins that implicated in health status and longevity. Therefore, targeting the SIRT1 signaling pathways may be a reasonable therapeutic approach to treat different diseases, including hepatic disorders. Flavonoids are polyphenolic compounds widely present in different plants and possess beneficial effects against diverse diseases. In this review, we focused on the flavonoids, (−)-epicatechin, ampelopsin, baicalin, delphinidin, fisetin, epigallocatechin-3-gallate, luteolin, pinocembrin, quercetin, silibinin, trans-chalcone and xanthohumol, to verify whether their potential promising hepatoprotective effects are related to activation of SIRT1. Additionally, molecular modeling simulations were applied to explore the potential binding mode of these flavonoids to SIRT1. The complied information and molecular docking simulations suggested that SIRT1 signaling is involved in the beneficial pharmacologic activities of flavonoids in different hepatic diseases.
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•Micellization of xanthohumol enhances its anti-inflammatory activity in adjuvant-induced arthritis.•Micellar xanthohumol was more potent than the native form in decreasing inflammatory cytokines and ...in exhibiting anti-oxidant activity.•Micellar xanthohumol showed in comparable doses to diclofenac similar efficacy in the chronic inflammation model.
Xanthohumol is known to exert anti-inflammatory properties but has poor oral bioavailability. Using advanced micellization technology, it has been possible to markedly enhance its bioavailability.
In the present study, we compared the chronic anti-inflammatory activities of native and micellar xanthohumol in the rat adjuvant arthritis model, using diclofenac as a reference drug.
Adjuvant arthritis was induced by injecting Freund's complete adjuvant into the right hind paw of rats and monitoring paw volume over 3 weeks. The drugs were given daily for 3 weeks, starting from the day of adjuvant inoculation. Serum was collected at the end of the experiment to measure inflammatory and oxidative stress parameters. Statistical comparisons between different groups were carried out by one-way analysis of variance followed by Tukey-Kramer multiple comparison test.
Micellar solubilized xanthohumol showed a better anti-inflammatory activity than its native form. The reduction in paw volume was reflected in corresponding changes in relevant mediators of inflammation like tumor necrosis factor-α, interleukin-6 and C-reactive protein, myloperoxidase and lipid peroxidation markers.
The findings confirm that micellar solubilization of xanthohumol enhances its anti-inflammatory activity, probably as a result of improving its bioavailabilty. The solubilized xanthohumol may prove to be a promising adjuvant tool for anti-inflammatory treatment and a potential anti-inflammatory alternative to synthetic drugs.
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Some of the most valuable bioactive compounds in beer comes from hops polyphenols, mainly flavonoids, some of which are unique to inflorescences of that flowering plant. Although far from ...pharmacologically relevant concentrations, low doses of xanthohumol and related prenylflavonoids found in beer contribute to the overall antioxidant activity of the product, as well as to significant chemopreventive action about certain diseases, such as cardiovascular, neurodegenerative, and some cancer types. Hence, the efforts to explore both ingredients and brewing methods aimed at enhancing the concentration of such bioactive compounds. In this study, a novel brewing method assisted by hydrodynamic cavitation was experimented, proving its ability to retain or generate higher amounts of xanthohumol, desmethylxanthohumol and 6-geranylnaringenin. Operational parameters, concerning hops processing, and leading to the enhanced retention, or generation, of the considered prenylflavonoids, were found to be common to all those same compounds. As well, basic mechanisms were hypothesized, such as increased extraction from hops, reduced adsorption to insoluble malt proteins, and reduced isomerization. The results expand recent evidence about enhanced extraction of bioactive compounds by processes based on hydrodynamic cavitation, as well as add to already proven benefits of hydrodynamic cavitation to the brewing processes.
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•HC-assisted brewing enhances concentration of hops prenylflavonoids in beer.•Time-temperature quantitative limits for HC-assisted hops processing are identified.•Enhanced extraction, and reduced adsorption to insoluble proteins, are hypothesized.•HC surprisingly effective in generating the prenylated flavanone 6-GN.•HC-assisted beer brewing promising for further enrichment with prenylflavonoids.
Xanthohumol (XN) and demethylxanthohumol (DMX) are specialized prenylated chalconoids with multiple pharmaceutical applications that accumulate to high levels in the glandular trichomes of hops ...(Humulus lupulus L.). Although all structural enzymes in the XN pathway have been functionally identified, biochemical mechanisms underlying highly efficient production of XN have not been fully resolved. In this study, we characterized two noncatalytic chalcone isomerase (CHI)-like proteins (designated as HlCHIL1 and HlCHIL2) using engineered yeast harboring all genes required for DMX production. HlCHIL2 increased DMX production by 2.3-fold, whereas HlCHIL1 significantly decreased DMX production by 30%. We show that CHIL2 is part of an active DMX biosynthetic metabolon in hop glandular trichomes that encompasses a chalcone synthase (CHS) and a membrane-bound prenyltransferase, and that type IV CHI-fold proteins of representative land plants contain conserved function to bind with CHS and enhance its activity. Binding assays and structural docking uncover a function of HlCHIL1 to bind DMX and naringenin chalcone to stabilize the ring-open configuration of these chalconoids. This study reveals the role of two HlCHILs in DMX biosynthesis in hops, and provides insight into their evolutionary development from the ancestral fatty acid-binding CHI-fold proteins to specialized auxiliary proteins supporting flavonoid biosynthesis in plants.
Prohibitin (PHB) was originally isolated and characterized as an anti-proliferative gene in rat liver. The evolutionarily conserved PHB gene encodes two human protein isoforms with molecular weights ...of ~33 kDa, PHB1 and PHB2. PHB1 and PHB2 belong to the prohibitin domain family, and both are widely distributed in different cellular compartments such as the mitochondria, nucleus, and cell membrane. Most studies have confirmed differential expression of PHB1 and PHB2 in cancers compared to corresponding normal tissues. Furthermore, studies verified that PHB1 and PHB2 are involved in the biological processes of tumorigenesis, including cancer cell proliferation, apoptosis, and metastasis. Two small molecule inhibitors, Rocaglamide (RocA) and fluorizoline, derived from medicinal plants, were demonstrated to interact directly with PHB1 and thus inhibit the interaction of PHB with Raf-1, impeding Raf-1/ERK signaling cascades and significantly suppressing cancer cell metastasis. In addition, a short peptide ERAP and a natural product xanthohumol were shown to target PHB2 directly and prohibit cancer progression in estrogen-dependent cancers. As more efficient biomarkers and targets are urgently needed for cancer diagnosis and treatment, here we summarize the functional role of prohibitin domain family proteins, focusing on PHB1 and PHB2 in tumorigenesis and cancer development, with the expectation that targeting the prohibitin domain family will offer more clues for cancer therapy.
Osteoarthritis (OA) is the most frequent and disabling disease in developed countries. The progressive degeneration of articular cartilage characterized as thinner and erosive. Inflammation is ...well-known to be involved in OA development. However, there are no effective therapeutic strategies to cure it. Xanthohumol (XH) is a natural prenylflavonoid isolated from hops and beer. The protective activity of XH against OA chondrocytes inflammation and ECM degradation is unclear. In this article, we found that XH significantly inhibited inflammatory responses, attenuated catabolic enzymes expression, and ameliorated ECM degradation, as showed by decreased production of NO, PGE2, TNFα, and IL-6, decreased expression of MMP-3/-13 and ADAMTS-4/-5, and increased expression of collagen-II and aggrecan. In addition, XH activated HO-1 signaling and attenuated IL-1β-induced C/EBPβ. XH promoted the interaction between HO-1 and C/EBPβ, inhibiting the nuclear translocation of C/EBPβ. HO-1 knockdown could abrogate the protective effects of XH in IL-1β-treated chondrocytes. Collectively, XH attenuated inflammatory responses and ECM degradation by mediating HO-1 and C/EBPβ signaling pathways in osteoarthritis chondrocytes.
Breast cancer is the most common type of cancer in women, and vast research is being conducted throughout the world for the treatment of this malignancy by natural products using various ...computational approaches. Xanthohumol, a prenylated flavonoid, is known for its anticancer activity; however, the mechanism behind its action is still in the preliminary stage.
The current study aimed to analyze the efficacy of xanthohumol compared to the currently available anticancer drugs targeting phosphoinositide-3-kinase (PI3K), serine/threonine kinase (AKT) receptors, and human epidermal growth factor receptor 2 (HER2) for breast cancer treatment through
analysis.
The result revealed that the target compound showed significant binding affinity to targets within the PI3K, AKT, and HER2 signaling pathways with a binding energy of -7.5, -7.9, and -7.9 kcal/mol, respectively. Further prediction studies were then made concerning this compound's absorption, distribution, metabolism, and excretion (ADME) as well as drug-likeness properties, resulting in its oral bioavailability with only a single violation of Lipinski's rule of five.
The finding revealed the ability of xanthohumol to bind with multiple cancer cell signaling molecules including PI3K, AKT kinase, and HER2. The current novel study opened the door to advancing research into the management and treatment of breast cancer.
In the present study a colon targeted liquisolid powder of xanthohumol was developed using Central Composite Design (CCD). Xanthohumol is a drug obtained from hops plants that can be effective in the ...treatment of UC. It possesses poor aqueous solubility, permeability and dissolution rate limited oral bioavailability. Hence, it was thought to enhance its dissolution rate by formulating liquisolid powder. Liquisolid technology is simple, single step and cost effective techniques to enhance dissolution rate of lipophilic drugs. Further, the formulation was targeted to colon using optimized combination of guar gum and pectin. Liquisolid powder of xanthohumol was formulated using Transcutol P as non-volatile solvent, polysaccharide mixture of guar gum and pectin as carrier, Syloid XDP as coating agent. The ratio of guar gum, pectin and Syloid XDP affecting angle of repose, drug loading and dissolution of drug in 5 h were optimized using CCD. The optimized formulation showed angle of repose of 26.78°, drug loading of 89.34% and dissolution of drug in 5 h of 5.23%, respectively. The formulation showed site-specific release of liquisolid with less than 10% drug release in initial 5 h due to the release restricting property of guar gum and pectin followed by a burst release of xanthohumol between 5th and 12th hour indicating colon specific release of xanthohumol. The powder X-ray diffraction studies, differential scanning calorimetry and scanning electron microscopy revealed about complete solubility of xanthohumol in the Transcutol P and complete adsorption of the liquid on surface of Syloid XDP, guar gum and pectin. The accelerated stability studies indicated that the formulation was stable. The overall results of study indicated about successful development of colon targeted liquisolid formulation of xanthohumol that can be further explored for pre-clinical studies.
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To map the chemodiversity of key bitter compounds in hops, a total of 75 different samples collected from the global hop market were analyzed for 117 key bitter tastants by means of a multiparametric ...HPLC-MS/MSMRM method. Among the compounds detected, 2″,3″-epoxyxanthohumol was detected for the first time in hops and isoxanthohumol M was identified as a marker compound for varieties grown in Germany. Hop aging experiments in the absence and presence of air oxygen, respectively, were conducted to address the stability of hop-derived compounds during long-term storage.
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