• YAKHAK HOEJI
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• v.54 no.6
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• pp.481-487
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• 2010

The proteasome plays a major role in the degradation of abnormal proteins within the cell. Therefore, repressed proteasome function is accepted as one of factors contributing the pathogenesis of multiple degenerative diseases. In the present study, we have observed that xanthohumol C, which is one of prenylated flavonoids from hops, increases the expression of the proteasome subunits through the Nrf2 pathway. Treatment of murine renal epithelial TCMK-1 cells with xanthohumol C and its methoxymethoxy-derivative elevated the expression of the Antioxidant Response Element (ARE)-driven reporter gene, as well as Nrf2-target genes including NAD(P)H: quinoneoxidoreductaes 1 (Nqo1). Transcript levels for the catalytic subunits of the proteasome Psmb5 and Psmb6 were increased by these compounds. The activation of the psmb5 promoter by xanthohumol C was abolished when the ARE in this promoter was mutated, indicating that proteasome induction was mediated by the Nrf2-ARE pathway. These results suggest that xanthohumol compounds from hops have a potential benefit on various oxidative stress-associated human diseases through the induction of the proteasome.

• Natural Product Sciences
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• v.18 no.4
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• pp.261-265
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• 2012

Xanthohumol was isolated from hops (Humulus lupulus L.), and then investigated anti-oxidant effect by AAPH-induced LLC-PK1 cell and oxygen radical absorbance capacity (ORCA) assays and MMP-12 inhibitory effect by direct MMP-12 inhibition assay. The treatment of xanthohumol protected LLC-PK1 cells from AAPH-induced cell damage such as cell viability, SOD and GSH-px reduction in a dose dependant manner (0.1, 1, and $5{\mu}M$), the SOD value was 2.98, 4.51, and 5.77 U/mg protein, and GSH-px value was 30.12, 49.32, and 60.11 U/mg protein. ORAC value of xanthohumol was showed as 4320, 12004, and $14209{\mu}M$ TE/g at the concentration 0.1, 1, and $5{\mu}M$, respectively. The change of SOD and GSH-px values was significantly correlated with the results of ORAC assay, that is, AAPH-induced cell and ORCA assays. In addition, inhibition of MMP-12 that is known to play an important role in skin aging was 14%, 37%, 46%, and 79% at the concentration of 0.01, 0.1, 1, and $5{\mu}M$, respectively. On the basis of these results, xanthohumol from hops (Humulus lupulus L.) showed interesting biological and pharmacological activity such as anti-oxidant effect and anti-aging.

• Biomolecules & Therapeutics
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• v.17 no.4
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• pp.422-429
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• 2009

Invasion and metastasis is the main cause of cancer mortality. Angiogenesis is a prerequisite for the tumor growth and metastasis. Matrix metalloproteinases (MMPs) are the key enzymes playing in the invasive growth and metastasis of cancer as well as angiogenesis. Xanthohumol, a prenylated chalcone of the Hop plant (Humulus lupulus L), has been reported to suppress cancer invasion and angiogenesis. In the present study, we investigated the antiinvasive effects of xanthohumol (1) and its synthetic derivatives, 4'-O-methylxanthohumol SEM ether (2), xanthohumol C (3), and xanthohumol C MOM ether (4) in relation to MMP expression in HT-1080 human fibrosarcoma cells. The compound 1 and its derivative, 3 and 4, significantly inhibited serum-induced HT-1080 cell invasion, and 12-O-tetradecanoylphorbol-13-acetate (TPA)-enhanced activity and expression level of MMP-2 and MMP-9 in a concentration-dependant manner. In addition, they inhibited TPA-enhanced expression of MT1-MMP with relatively weak inhibition in tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 level. The compound 1 significantly decreased the cell viability, whereas the derivatives, 2 and 3 showed no cytotoxicity, and compound 4 showed slight cytotoxicity in the cells. Furthermore, in a chick chorioallantoic membrane (CAM) assay, the derivatives 3 and 4 dose-dependently suppressed vascular endothelial growth factor (VEGF)-induced angiogenesis, which is similar to that of compound 1. Taken together, the results indicate that compounds 3 and 4 may be valuable anti-angiogenic agents in the treatment of chronic diseases such as cancer and inflammation working through suppression of MMP-2 and MMP-9.

• YAKHAK HOEJI
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• v.54 no.1
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• pp.27-31
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• 2010

Xanthohumol, a prenylated chalcone of the Hop plant (Humulus lupulus L.), has been reported to suppress tumor growth. 4-hydroxychalcone and isobavachalcone are chalcone derivatives and they have similar structure with xanthohumol. In the present study, we investigated the cytotoxic activities of chalcone and its derivatives, 4-hydroxychalcone, xanthohumol, and isobavachalcone, in MCF-7 and adriamycin resistant MCF-7 (MCF-7/ADR) breast cancer cells and HT-1080 fibrosarcoma cells. In a cell viability assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reagent, chalcone and 4-hydroxychalcone decreased cell viability in HT-1080 cells, but not in MCF-7 and MCF-7/ADR cells. Isobavachalcone showed similar cytotoxicity in HT-1080 cells, and only limited cytotoxicity in MCF-7 and MCF-7/ADR cells at very high concentration (50 ${\mu}M$). In contrast, xanthohumol showed concentration-dependent cytotoxicity in MCF-7, MCF-7/ADR, and HT-1080 cancer cells. Taken together, the structure-activity relationship of chalcone and its derivatives indicate that chalcones may be valuable cytotoxic compounds against selective cancer types.

• Bulletin of the Korean Chemical Society
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• v.29 no.6
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• pp.1205-1210
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• 2008

A new and efficient synthetic approach is reported for biologically interesting prenylated chalcones, 4'-Omethylxanthohumol (3), xanthohumol E (4), and sericone (5) from 2,4,6-trihydroxyacetophenone. The strategies involve the introduction of a prenyl group onto an aryl ring, benzopyran formation, and basecatalyzed aldol reactions.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.35-36
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• 2001

Nutrition influences cancer incidence and offers a variety of preventive dietary factors including non-nutritive plant metabolites. To identify novel potential chemopreventive agents, we have set up cell- and enzyme-based in vitro marker systems relevant for prevention of carcinogenesis in vivo. This experimental approach led to the identification of Xanthohumol (Xn), a prenylated chalcone from hop (Humulus lupulus L.) as a most promising broad-spectrum chemopreventive agent.(omitted)

• BMB Reports
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• v.39 no.4
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• pp.383-393
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• 2006

Little is known concerning the mechanisms responsible for the transplacental transfer of thiamine. So, the aim of this work was to characterize the placental uptake of thiamine from the maternal circulation, by determining the characteristics of $^3H$-thiamine uptake by a human trophoblast cell line (BeWo). Uptake of $^3H$-thiamine (50-100 nM) by BeWo cells was: 1) temperature-dependent and energy-independent; 2) pH-dependent (uptake increased as the extracellular medium pH decreased); 3) $Na^+$-dependent and $Cl^-$-independent; 4) not inhibited by the thiamine structural analogs amprolium, oxythiamine and thiamine pyrophosphate; 5) inhibited by the unrelated organic cations guanidine, N-methylnicotinamide, tetraethylammonium, clonidine and cimetidine; 6) inhibited by the organic cation serotonin, and by two selective inhibitors of the serotonin plasmalemmal transporter (hSERT), fluoxetine and desipramine. We conclude that $^3H$-thiamine uptake by BeWo cells seems to occur through a process distinct from thiamine transporter-1 (hThTr-1) and thiamine transporter-2 (hThTr-2). Rather, it seems to involve hSERT. Moreover, chronic (48 h) exposure of cells to caffeine ($1\;{\mu}M$) stimulated and chronic exposure to xanthohumol and iso-xanthohumol (1 and $0.1\;{\mu}M$, respectively) inhibited $^3H$-thiamine uptake, these effects being not mediated through modulation of the expression levels of either hThTr-1 or hSERT mRNA.

• Korean Journal of Pharmacognosy
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• v.49 no.3
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• pp.189-202
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• 2018

Hop cones (Humuli Strobili) are the female inflorescences of hop plants (Humulus lupulus L.) belonging to the family Cannabaceae. They have been used as herbal remedies to treat mood and sleep disturbances, and mainly to add as a bittering ingredient in brewing process. Considerable interests on pharmacological and biological activities of hop cones have been focused on their major constituents, namely, phloroglucinols (humulone, lupulone), terpenes (myrcene, humulene), and prenylated flavonoids (xanthohumol, isoxanthohumol, 6-prenylnaringenin, and 8-prenylnaringenin). The present review describes and discusses biological activity profiles of these major compounds in the hop cones.

• Archives of Pharmacal Research
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• v.28 no.5
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• pp.534-540
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• 2005

Activity-guided fractionation of the CH$_2Cl_2$-soluble fraction of the roots of Sophora flavescens furnished five 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scaveng ers: trans-hexadecyl ferulic acid (1) cis-octadecyl ferulic acid (2), trans-hexadecyl sinapic acid (3), (-)-4-hydroxy-3-methoxy-(6aR,11aR)-8, 9-methylenedioxypterocarpan (4) and desmethylanhydroicaritin (8), along with nine known inactive compounds: (-)-maackiain (5), xanthohumol (6), formononetin (7), (2S)-2'-methoxykurarinone (9), (2S)-3${\beta}$,7,4'-trihydroxy-5-methoxy-8-(${\gamma},{\gamma}$- imethylallyl )-flavanone (10), (2S)-7,4'-dihydroxy-5-methoxy-8- (${\gamma},{\gamma}$-dimethylallyl ) -flavanone (11), umbelliferone (12), kuraridin (13), and trifolirhizin (14). Compounds 1-4 and 8 exhibited DPPH free radical scavenging effects at IC$_{50}$ values of 33.01 ${\pm}$ 0.20, 57.06 ${\pm}$ 0.16, 39.84 ${\pm}$ 0.36, 35.83 ${\pm}$ 0.47, and 18.11 ${\pm}$ 0.04${\mu}$M, respectively. L-Ascorbic acid, when used as a positive control, exhibited an IC$_{50}$ value of 7.39 ${\pm}$ 0.01 ${\mu}$M. Compounds 1-4 and 8 also appeared to exert significant scavenging effects on authentic ONOO-, with IC$_{50}$ values of 5.76 ${\pm}$ 1.19, 15.06 ${\pm}$ 1.64, 8.17 ${\pm}$ 4.97, 1.95 ${\pm}$ 0.29 and 4.06 ${\pm}$ 2.41 ${\mu}$M, respectively. Penicillamine (IC$_{50}$= 2.36 ${\pm}$ 0.79${\mu}$M) was used as a positive control. In addition, compounds 2,4,6,8, and 10 were isolated from this plant for the first time.