Xanthohumol for Human Malignancies: Chemistry,Pharmacokinetics and Molecular Targets

Xanthohumol (XH) is an important prenylated flavonoid that is found within the inflorescence of Humulus lupulus 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.     

Key Enzymes Involved in the Synthesis of Hops Phytochemical Compounds: From Structure,Functions to Applications

Humulus lupulus 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 Potent Phytoestrogen 8-Prenylnaringenin: A Friend or a Foe?

8-prenylnaringenin (8-PN) is a prenylated flavonoid, occurring, in particular, in hop, but also in other plants. It has proven to be one of the most potent phytoestrogens in vitro known to date, and in the past 20 years, research has unveiled new effects triggered by it in biological systems. These findings have aroused the hopes, expectations, and enthusiasm of a “wonder-drug” for a host of human diseases. However, the majority of 8-PN effects require such high concentrations that they cannot be reached by normal dietary exposure, only pharmacologically; thus, adverse impacts may also emerge. Here, we provide a comprehensive and up-to-date review on this fascinating compound, with special reference to the range of beneficial and untoward health consequences that may ensue from exposure to it.     

Influence of malt on the xanthohumol and isoxanthohumol behavior in pale and dark beers: A micro-scale approach

The main objective of this work was to understand which compounds are responsible for the partial inhibition of xanthohumol (XN) thermal isomerization during wort boiling of dark malts. With such purpose, worts from different kinds of malt (pale, caramel and roasted) were chemically characterized (e.g. antioxidant activity, polyphenols and melanoidins contents) and studied by several chromatographic techniques. Molecular exclusion chromatography experiments showed that adsorption of XN to polyvinylpolypyrrolidone is lower for the high molecular weight fractions. It seems likely that this is due to the reaction between XN and coloured substances that changes chemical properties of XN or, at least, results in the formation of complexes that have different chemical properties. This leads to an inhibition of XN isomerization observed in this work. It was also verified that the melanoidins content was significantly higher in the higher molecular weight fractions, suggesting that probably these compounds are the main responsible for the XN isomerization inhibiting effect.     

大孔树脂纯化废酒花黄腐酚及其抗DNA氧化损伤的活性

采用大孔树脂从酿造废酒花中分离纯化黄腐酚,并且检测了黄腐酚抗DNA氧化损伤的活性。结果表明:HPD100A树脂对黄腐酚的吸附率为100%,解吸率为77.69%,适合于废酒花黄腐酚的纯化。最佳工艺条件为:上样液黄腐酚质量浓度0.25mg/m L、上样量15BV、上样液p H5.5、上样流速2BV/h,洗脱剂为95%乙醇,洗脱流速2BV/h,洗脱剂用量3BV。在此条件下,可将黄腐酚纯度由纯化前的4.95%提高为51.50%,回收率为72.56%。结果表明,分离得到的黄腐酚纯化物对Phen-Cu SO4-VC诱导DNA氧化损伤的抑制作用（EC50为0.22mg/m L）显著优于抗坏血酸（EC50为0.51mg/m L）和芦丁（EC50为0.93mg/m L）,具有显著地抗DNA氧化损伤活性。      

分离纯化酒花黄腐酚初探

为了简化工艺,降低纯化黄腐酚的成本,将粉碎后的酒花先用超临界CO2萃取,收集酒花萃余物,以甲醇(乙醇)作为提取剂,对酒花萃余物进行超声波提取;浓缩的萃取液,与硅藻土混合均匀,先后经2种洗脱液洗脱,将收集到的第2种洗脱液经过滤膜过滤、低温浓缩干燥处理后,即可得到黄腐酚纯品,纯度为86.2%。纯化后的黄腐酚为黄色粉末状固体,经重结晶纯度可达97.8%以上。     

Number and size of lupulin glands,glandular trichomes of hop (Humulus lupulus L.), play a key role in contents of bitter acids and polyphenols in hop cone

Hop (Humulus lupulus L.) inflorescence, commonly known as ‘hop cone’, is valuable for contents of bitter acids, essential oils and polyphenols, used in brewing industry and biomedical application. These compounds are predominantly formed in glandular trichomes, known as ‘lupulin glands’. In this study, we investigated chemical and morphological characteristics of lupulin glands by microscopy and HPLC analyses. Even though no significant correlations were found between lupulin glands and hop cones for contents of alpha and beta bitter acids, polyphenols, all ratios between individual metabolites (alpha/beta acids, X/alpha acids, X/DMX) were highly and significantly correlated. The average number of lupulin glands on bract/bracteole ranged from 115 to 713 with 28.5% of variability. Linear regression analyses confirmed that total volume of lupulin glands and total lupulin glands area on bract/bracteole surface highly correlated with contents of bitter acids and polyphenols in hop cone. Therefore, lupulin glands are unique and exclusive organs responsible for contents of bitter acids and polyphenols in hop cone.     

不同光照条件对啤酒花中黄腐酚异构化影响

目的研究不同光照条件,如光照强度、光照时间、处理光的波长等因素对啤酒花中黄腐酚(xanthohumol,Xn)光异构化的影响。方法啤酒花样品在不同光照强度、光照时间、波长和不同颜色玻璃瓶储藏条件下处理后,于OD_(370)处测量Xn含量。结果相同功率光源的紫外光引起Xn异构化较白光显著(P0.05),白光照射Xn样品随着光照时间和光照强度的增大,Xn光异构化程度提高;相同功率光源及光照时间条件下,红光[(625±5)nm]、黄光[(590±5) nm]、绿光[(555±5)nm]、蓝光[(450±5)nm]处理引起的Xn异构化速度差异极显著(P0.01),其中蓝光最强,其次是绿光、红光、黄光;白光光源光照条件下,深棕色玻璃瓶储存对Xn的稳定性显著优于绿色、蓝色、无色玻璃瓶等(P0.05),并且深棕色玻璃瓶长期储存Xn显著优于绿色玻璃瓶(P0.05)。结论光照时间、波长及储存条件对Xn光异构化有显著的影响,且避光储存利于Xn稳定,这为含有Xn的饮品、食品、保健品等的光照或包装条件的选择提供了依据。     

啤酒花中黄腐酚的生理活性作用的研究进展

黄腐酚为酒花中主要的异戊二烯基黄酮类物质。目前被发现仅存在于酒花中,其含量占酒花干重的0.1%～1%,它的结构赋予它多重生理活性。本文综述了近年来对酒花中黄腐酚的提取、分离纯化、结构鉴定、以及抗癌、抗病毒、预防动脉样硬化和糖尿病、雌性激素、抗氧化等生理活性及其作用机理的研究进展。