The hop constituent xanthohumol exhibits hepatoprotective effects and inhibits the activation of hepatic stellate cells at different levels

Ralf Weiskirchen,^1,† Abdo Mahli,^2,† Sabine Weiskirchen,¹ and  Claus Hellerbrand^2,*.

Front Physiol. 2015; 6: 140. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422013/

Xanthohumol is the principal prenylated flavonoid of the female inflorescences of the hop plant. In recent years, various beneficial xanthohumol effects including anti-inflammatory, antioxidant, hypoglycemic activities, and anticancer effects have been revealed. This review summarizes present studies indicating that xanthohumol also inhibits several critical pathophysiological steps during the development and course of chronic liver disease, including the activation and pro-fibrogenic genotype of hepatic stellate cells. Also the various mechanism of action and molecular targets of the beneficial xanthohumol effects will be described. Furthermore, the potential use of xanthohumol or a xanthohumol-enriched hop extract as therapeutic agent to combat the progression of chronic liver disease will be discussed. It is notable that in addition to its hepatoprotective effects, xanthohumol also holds promise as a therapeutic agent for treating obesity, dysregulation of glucose metabolism and other components of the metabolic syndrome including hepatic steatosis. Thus, therapeutic xanthohumol application appears as a promising strategy, particularly in obese patients, to inhibit the development as well as the progression of non-alcoholic fatty liver disease.

Xanthohumol from Hop: Hope for cancer prevention and treatment

Sosmitha Girisa ¹, Queen Saikia ¹, Devivasha Bordoloi ¹, Kishore Banik ¹, Javadi Monisha ¹, Uzini Devi Daimary ¹, Elika Verma ¹, Kwang Seok Ahn ², Ajaikumar B Kunnumakkara ¹2021 Aug;73(8); https://pubmed.ncbi.nlm.nih.gov/34170599/

Cancer is a major public health concern due to high mortality and poor quality of life of patients. Despite the availability of advanced therapeutic interventions, most treatment modalities are not efficacious, very expensive, and cause several adverse side effects. The factors such as drug resistance, lack of specificity, and low efficacy of the cancer drugs necessitate developing alternative strategies for the prevention and treatment of this disease. Xanthohumol (XN), a prenylated chalcone present in Hop (Humulus lupulus), has been found to possess prominent activities against aging, diabetes, inflammation, microbial infection, and cancer. Thus, this manuscript thoroughly reviews the literature on the anti-cancer properties of XN and its various molecular targets. XN was found to exert its inhibitory effect on the growth and proliferation of cancer cells via modulation of multiple signaling pathways such as Akt, AMPK, ERK, IGFBP2, NF-κB, and STAT3, and also modulates various proteins such as Notch1, caspases, MMPs, Bcl-2, cyclin D1, oxidative stress markers, tumor-suppressor proteins, and miRNAs. Thus, these reports suggest that XN possesses enormous therapeutic potential against various cancers and could be potentially used as a multi-targeted anti-cancer agent with minimal adverse effects.

Xanthohumol for Human Malignancies: Chemistry, Pharmacokinetics and Molecular Targets

Vancha Harish ¹, Effi Haque ², Magdalena Śmiech ², Hiroaki Taniguchi ², Sarah Jamieson ³, Devesh Tewari ⁴, Anupam Bishayee ³   2021 Apr 25;22(9) https://pubmed.ncbi.nlm.nih.gov/33923053/

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.

Antioxidants in Hops: Bioavailability, Health Effects and Perspectives for New Products

Corina-Aurelia Zugravu ¹, Roxana-Elena Bohiltea ², Teodor Salmen ³, Elena Pogurschi ⁴, Marina Ruxandra Otelea ⁵  2022 Jan 27; https://pubmed.ncbi.nlm.nih.gov/35204124/

Hop plant (Humulus lupulus L.) has been used by humans for ages, presumably first as a herbal remedy, then in the manufacturing of different products, from which beer is the most largely consumed. Female hops cones have different useful chemical compounds, an important class being antioxidants, mainly polyphenols. This narrative review describes the main antioxidants in hops, their bioavailability and biological effects, and the results obtained by now in the primary and secondary prevention of several non-communicable diseases, such as the metabolic syndrome related diseases and oncology. This article presents in vitro and in vivo data in order to better understand what was accomplished in terms of knowledge and practice, and what needs to be clarified by additional studies, mainly regarding xantohumol and its derivates, as well as regarding the bitter acids of hops. The multiple protective effects found by different studies are hindered up to now by the low bioavailability of some of the main antioxidants in hops. However, there are new promising products with important health effects and perspectives of use as food supplements, in a market where consumers increasingly search for products originating directly from plants.

Flavonoids as Phytoestrogenic Components of Hops and Beer

Tomasz Tronina ¹, Jarosław Popłoński ¹, Agnieszka Bartmańska ¹  2020 Sep 14;25(18; https://pubmed.ncbi.nlm.nih.gov/32937790/

The value of hops (Humulus lupulus L.) in beer production has been undisputed for centuries. Hops is rich in humulones and lupulones which gives the characteristic aroma and bitter taste, and preserves this golden drink against growing bacteria and molds. Besides α- and β-acids, the lupulin glands of hop cones excrete prenylated flavonoids, which exhibit a broad spectrum of biological activities and therefore has therapeutic potential in humans. Recently, interest in hops was raised due to hop prenylated flavanones which show extraordinary estrogen activities. The strongest known phytoestrogen so far is 8-prenylnaringenin (8-PN), which along with 6-prenylanaringenin (6-PN), 6,8-diprenylnaringenin (6,8-DPN) and 8-geranylnaringenin (8-GN) are fundamental for the potent estrogen activity of hops. This review provides insight into the unusual hop phytoestrogens and shows numerous health benefits associated with their wide spectrum of biological activities including estrogenic, anticancer, neuropreventive, antinflamatory, and antimicrobial properties, which were intensively studied, and potential applications of these compounds such as, as an alternative to hormone replacement therapy (HRT).

Fundamentals and health benefits of xanthohumol, a natural product derived from hops and beer

Paulo J Magalhães ¹, Daniel O Carvalho, José M Cruz, Luís F Guido, Aquiles A Barros 2009 May;4(5): https://pubmed.ncbi.nlm.nih.gov/19445313/

In recent years, there has been a growing interest in phenolic compounds and their presumed role in the prevention of various degenerative diseases, such as cancer and cardiovascular diseases. Xanthohumol, a prenylated chalcone from hops and beer, is among the phenolic compounds which have received the most attention in recent years. This compound has a range of interesting biological properties that may have therapeutic utility. Based on the health-promoting properties of xanthohumol, the production of a beer enriched in this substance would be of huge interest to the brewing industry, for the benefits this could bring to consumer’s health. This paper reviews recent and important data with respect to the health benefits or biological activities of xanthohumol and beer. In addition, an overview of the chemistry and biotechnological aspects of xanthohumol is presented.

Xanthohumol microbiome and signature in healthy adults (the XMaS trial): a phase I triple-masked, placebo-controlled clinical trial

Ryan Bradley ¹, Blake O Langley ², Jennifer J Ryan ², John Phipps ², Douglas A Hanes ², Emily Stack ², Janet K Jansson ³, Thomas O Metz ³, Jan Frederik Stevens ⁴    . 2020 Oct 7;21; https://pubmed.ncbi.nlm.nih.gov/33028396/

Background: Natural products may provide a source for the discovery and development of adjunctive pharmacological interventions to modulate the inflammatory pathways contributing to chronic disease. Xanthohumol, a flavonoid from the hops plant (Humulus lupulus), has antioxidant and anti-inflammatory properties and may act as a prebiotic to the intestinal microbiota. Xanthohumol is not currently approved as a drug by the US Food and Drug Administration (FDA), but is available as a dietary supplement and ingredient in medical foods. To formally test the safety of xanthohumol, a phase I clinical trial (“XMaS”) was designed and approved under an Investigational New Drug application to the US FDA. The main objective is to examine the clinical safety and subjective tolerability of xanthohumol in healthy adults compared to placebo. Additional aims are to monitor biomarkers related to inflammation, gut permeability, bile acid metabolism, routes, and in vivo products of xanthohumol metabolism, and to evaluate xanthohumol’s impact on gut microbial composition.