A first prospective, randomized, double-blind, placebo-controlled study on the use of a standardized hop extract to alleviate menopausal discomforts

Heyerick, Arne; Vervarcke, Stefaan; Depypere, Herman; Bracke, Marc; Keukeleire, Denis De

doi:10.1016/j.maturitas.2005.10.005

Cited by 137 publications

(105 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore there were no statistical tests reported, and some subjects received a second herb in addition to H. lupulus. The second report tested two H. lupulus extracts with different concentrations of 8-PN using a standardized extract [29]. They found that the lower dose of 8-PN (100 μg 8-PN/ dose) had a significant reduction of the Kuiper Index at six weeks, but not at 12 weeks, and the higher dose (250 μg 8-PN/dose) was not significant at either time point [29].…”

Section: Discussionmentioning

confidence: 99%

“…While H. lupulus extracts have also been tested in two phase I clinical trials in menopausal women [29], extracts have not been rigorously tested in vivo following the identification of 8-PN as the compound primarily responsible for estrogenic activity. The authors of the in vivo animal study found that a high dose of 8-PN (68.4 mg/kg) had an estrogenic effect by suppressing serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) and body weight gain, and stimulated serum prolactin levels, uterus weight, and the mRNA transcription levels of the progesterone receptor, insulin-like growth factor I, and complement protein C3 [27], Additionally, the high dose of 8-PN was reported separately to have histological features similar to the estrogen control, and induced epithelial polyploidy formation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In vivo estrogenic comparisons of Trifolium pratense (red clover) Humulus lupulus (hops), and the pure compounds isoxanthohumol and 8-prenylnaringenin

Overk

Guo

Chadwick

et al. 2008

Chemico-Biological Interactions

View full text Add to dashboard Cite

The lack of a safe and reliable alternative to hormone therapy (HT) for treating menopausal symptoms underscores the need for alternative therapies. OBJECTIVE: The purpose of this study was to assess the in vivo estrogenic effects of the botanical dietary supplements Trifolium pratense (red clover) and Humulus lupulus (hops), and two compounds obtained from H. lupulus, isoxanthohumol and 8-prenylnaringenin (8-PN) using the ovariectomized uterotrophic adult rat model. A H. lupulus extract and a 30% isoflavone extract of T. pratense were tested at three escalating doses as was one dose of isoxanthohumol for 21 days. 8-Prenylnaringenin, the major estrogen in H. lupulus, was also tested at three relevant escalating doses. In order to determine the in vivo metabolism of 8-PN, the major Phase I and Phase II metabolites were also identified. The primary outcome measure, uterus weight gain, indicated that H. lupulus and T. pratense did not have an estrogenic effect on the uterus, and none of the secondary outcome measures were positive. In contrast, there was a clear dose response when 8-PN was evaluated where the middle and high doses of 8-PN were active. 8-Prenylnaringenin in rat plasma, liver, and mammary gland was measured and the major Phase I and Phase II 8-PN metabolites were detected. Our findings suggest that while both the H. lupulus and T. pratense extracts do not have an effect on the rat uterus, 8-PN at equivalent doses to those previously used in humans did have an effect, and may therefore have a deleterious effect in women. IntroductionSymptoms associated with menopause such as insomnia, loss of libido, vaginal atrophy, depression, and hot flashes can greatly affect the quality of life for women. Many women have used hormone therapy (HT) to alleviate menopausal symptoms; however, with the publication The strobiles of Humulus lupulus L. (Cannabaceae) (hops) are primarily used to flavor beer, and have been studied since 1953 for a potential estrogenic mechanism of action [13][14][15]. In the past, the flavonoids 8-PN and 6-PN, and the chalcone, isoxanthohumol (IX), have been isolated and reported to be estrogenic in vitro and/or in vivo [16,17]. The most potent estrogen in H. lupulus is 8-PN, which is in actuality an artifact formed through isomerization of the precursor chalcone, desmethylxanthohumol [18,19]. 8-Prenylnaringenin has been shown in a variety of in vitro assays to be estrogenic in the nanomolar range [16,17,20,21]. It can also be formed from precursors such as IX, and xanthohumol (XH), through metabolism [22].In previous metabolic studies, it has been shown that human liver microsomes convert 8-PN to 12 metabolites [22]. Among them, are the most abundant monooxygenated metabolites (Figure 1). The estrogenicities of the 8-PN alcohols have been previously determined [23] and were found to be ∼10 fold less estrogenic than 8-PN. Phase II metabolites of 8-PN, including glucuronides and sulfate conjugates, have been identified in incubations with human Caco-2 cells and human hepatocytes [2...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vivo estrogenic comparisons of Trifolium pratense (red clover) Humulus lupulus (hops), and the pure compounds isoxanthohumol and 8-prenylnaringenin

Overk

Guo

Chadwick

et al. 2008

Chemico-Biological Interactions

View full text Add to dashboard Cite

show abstract

“…The presence of prenylated Favonoids made SF extract to facilitate the elimination of a variety of xenobiotics including pollutants, carcinogens, and drugs by oxidative metabolism (Ueng et al, 2009). A first prospective, randomized, double-blind and placebo-controlled study has been done to investigate how the prenylated flavonoid, 8-PN, alleviated menopausal discomforts (Heyerick et al, 2006). Sixty-seven menopausal women were treated with 8-PN for over 12 weeks.…”

Section: Summary Of the Current Situation On Both In Vivo And In Vitrmentioning

confidence: 99%

A systematic review on biological activities of prenylated flavonoids

Chen

Mukwaya

Wong

et al. 2013

Pharmaceutical Biology

185

136

View full text Add to dashboard Cite

Context: Prenylated flavonoids are a unique class of naturally occurring flavonoids that exist especially for the plant's self-defensive strategy. This special class of flavonoids increases the bioactivities of their backbone flavonoids with non-prenylation; therefore, prenylated flavonoids have more potential to be developed and utilized. Objective: The number, position and type of the prenyl group on the flavonoids backbone structure may have close relationships with the bioactivities of flavonoids. Methods: PubMed and WEB OF KNOWLEDGEÕ were used to search articles published in English between 1 January 2002 and 31 December 2012, which discuss the structure-activity relationship between prenylated flavonoids and their bioactivities. Results: It is proposed that the prenyl-moiety makes the backbone compound more lipophilic, which leads to its high affinity with cell membranes. The prenylation brings the flavonoids with enhancement of antibacterial, anti-inflammatory, antioxidant, cytotoxicity, larvicidal as well as estrogenic activities. However, it is reported that the prenyl-moiety decreases the bioavailability and plasma absorption of prenylated flavonoids. Conclusion: The prenyl group affects the bioactivities of flavonoids in certain ways, while the action mechanisms and the structure-activity relationship as well as more in vivo studies even clinical validation trials need to be further investigated.

show abstract

“…Isoxanthohumol, jehož přeměna na fytoestrogenní 8-prenylnaringenin (hopein) působením bakterií Eubacterium limosum lidské střevní mikroflóry byla doložena v několika studiích (Possemiers et al, 2005(Possemiers et al, , 2011, je nadále středem zájmu jako medikament zmírňující symptomy menopauzy (např. Heyerick et al, 2006, Erkkola et al, 2010. I když hopein i některé jiné chmelové medikamenty jsou již uvedeny na trh v souvislosti s farmaceutickým využitím chmelu (viz např.…”

unclassified

“…Isoxanthohumol whose conversion to phytoestrogenic 8-prenylnaringenin (hopein) facilitated by the human intestinal microflora (Eubacterium limosum) described in several studies (Possemiers et al, 2005(Possemiers et al, , 2011 continued to be of great interest as the medicament facilitating menopausal symptoms (e.g. Heyerick et al,2006;Erkkola et al, 2010). Although hopein and some other hop medicaments has been in connection to the medicinal use of hop introduced to the market (see e.g.…”

mentioning

confidence: 99%

"Transgenic" metabolome of hop, some aspects of its development and prospects of utilization.

Matoušek¹

2012

Kvasny Prum

View full text Add to dashboard Cite

Chmel, který je pěstován hlavně pro kvasný průmysl jako zdroj cenných sekundárních metabolitů lupulinu dodávajících pivu charakteristickou hořkost a aroma, produkuje metabolom obsahující látky s protinádorovou, antiangiogenní i estrogenní aktivitou, kam patří zejména prenylflavonoidy jako xanthohumol. Získat odrůdy s vyšším obsahem xanthohumolu proto patří k současnému úsilí šlechtitelů. Předpokládá se, že hladinu těchto látek, která se pohybuje u nejlepších šlechtitelských materiálů v intervalu 1-2%, by pomohl zvýšit "transgenní metabolom" s využitím biotechnologie pomocí nově identifikovaných lupulin-specifických genů i transkripčních faktorů z rodin Myb, bZip, WD40 a bHLH a WRKY, které se podílejí na jejich regulacích. V současnosti byl na základě našich studií zjištěn komplexní charakter regulace biosyntetické dráhy prenylflavonoidů s účastí tzv. ternárních i binárních komplexů, pozitivních regulátorů i supresoru transkripce. Tyto poznatky umožní cílené transformace chmelu pro přípravu transgenního metabolomu i s perspektivou indukce metabolicky aktivních transgenních pletiv v tkáňových kulturách. Faktická využitelnost transgenního metabolomu chmelu půjde ruku v ruce s poznatky základního výzkumu o metabolických drahách lupulinu, které budou postupně zahrnovat nejen produkci polyfenolů, ale i hoř-kých a aromatických látek i s uvědoměním si nových praktických výhod GMO ve společnosti. Hop, which is mainly cultivated for the brewing industry, as a source of flavor-active secondary metabolites providing desired bitterness and aroma to beer, produces the metabolome containing compounds beneficial for human health. These are mainly prenylflavonoids as Xanthohumol, with anticancerogenic, antiangiogenic and estrogenic activities. It is the recent effort of breeders to gain new hop cultivars with higher level of Xanthohumol. It is expected that the level of these compounds which reaches just 1-2% in the best breeding materials, could be enhanced in "transgenic metabolome" introduced by the biotechnology with the use of newly identified lupulin-specific genes and transcription factors (TF) from Myb, bZip, WD40 and bHLH families that participate in their regulations. At present, we found complex character of regulation of prenylflavonoid bio-synthetic pathway including an involvement of so-called ternary and binary TF complexes, positive regulators, as well as transcription suppressor. This knowledge enables targeted hop transformation for the preparation of transgenic metabolome and makes realistic the perspective to induce metabolically active transgenic tissue cultures of hop. An effective usefulness of transgenic metabolome of hop will depend on their findings of basic research in the metabolic pathways of lupulin and social awareness with a new practical benefit of GMO, that will include successively not only production of polyphenols, but also bitter acids and aromatic compounds. Der Hopfen, der hauptsächlich für die Gärungsindustrie als die Quelle von wertvollen sekundären Metabolite des Lupulins, die dem Bier ...

show abstract

A first prospective, randomized, double-blind, placebo-controlled study on the use of a standardized hop extract to alleviate menopausal discomforts

Cited by 137 publications

References 38 publications

In vivo estrogenic comparisons of Trifolium pratense (red clover) Humulus lupulus (hops), and the pure compounds isoxanthohumol and 8-prenylnaringenin

In vivo estrogenic comparisons of Trifolium pratense (red clover) Humulus lupulus (hops), and the pure compounds isoxanthohumol and 8-prenylnaringenin

A systematic review on biological activities of prenylated flavonoids

"Transgenic" metabolome of hop, some aspects of its development and prospects of utilization.

Contact Info

Product

Resources

About