Hop extracts and their utilizations: perspectives based on the last 10 years of research

Rosa, Raul Santiago; Lannes, Suzana Caetano da Silva

doi:10.1590/s2175-97902024e23905

Raul Santiago Rosa ^**Correspondence: R. S. Rosa. E-mail: raul.rosa@usp.br .

was responsible for the idea, literature search, draft, analysis, and bibliometric mapping

Department of Biochemical-Pharmaceutical Technology, Faculty of Pharmaceutical Sciences of University of São Paulo, São Paulo, São Paulo, Brazil

https://orcid.org/0000-0003-3164-5568

Suzana Caetano da Silva Lannes S. C. da S. Lannes. E-mail: scslan@usp.br .

was responsible for critically reviewing the work and suggestions of exclusion criteria

Department of Biochemical-Pharmaceutical Technology, Faculty of Pharmaceutical Sciences of University of São Paulo, São Paulo, São Paulo, Brazil

https://orcid.org/0000-0002-4481-7376

*Correspondence: R. S. Rosa. E-mail: raul.rosa@usp.br .

S. C. da S. Lannes. E-mail: scslan@usp.br .

Competing interests The authors have no competing interests to declare that are relevant to the content of this article.

Application	Technology	Effect
Bread	Extraction in water or milk at 90-95°C	Increases strength and quality of flours low in gluten. (Sokolova, 2021 Sokolova N. Effect of hop extracts on rheological properties of wheat dough. IOP Conf Ser Mater Sci Eng. 2021; 1031: 012097. https://doi.org/10.1088/1757-899X/1031/1/012097 . https://doi.org/10.1088/1757-899X/1031/1... )
Bread and heterofermentative bread (sourdough)	Aqueous extract (boil, 1h)	Increase in polyphenol content, antioxidant activity and total amino acids.
Bread and heterofermentative bread (sourdough)	Aqueous extract (boil, 1h)	Change in the taste and color of the crust (Nionelli et al. , 2018 Nionelli L, Pontonio E, Gobbetti M, Rizzello CG. Use of hop extract as antifungal ingredient for bread making and selection of autochthonous resistant starters for sourdough fermentation. Int J Food Microbiol. 2018; 266: 173–82. https://doi.org/10.1016/j.ijfoodmicro.2017.12.002 . https://doi.org/10.1016/j.ijfoodmicro.20... )
Bread with rice bran and heterofermentative bread (sourdough)	Aqueous extract (water boiled for 6 hours then room temperature)	Increased antioxidant activity and total polyphenols in conjunction with rice bran. (Irakli et al. , 2019 Irakli M, Mygdalia A, Chatzopoulou P, Katsantonis D. Impact of the combination of sourdough fermentation and hop extract addition on baking properties, antioxidant capacity and phenolics bioaccessibility of rice bran-enhanced bread. Food Chem. 2019; 285: 231–9. https://doi.org/10.1016/j.foodchem.2019.01.145 . https://doi.org/10.1016/j.foodchem.2019.... )
Lamb patty	Extraction in 2g/50ml boiling H2O and dispersion in natura (hop powder) unfiltered.	Increased antioxidant activity; reduction of lipid and protein oxidation; increased color stability during storage (Villalobos-Delgado et al. , 2015 Villalobos-Delgado LH, Caro I, Blanco C, Bodas R, Andrés S, Giráldez FJ, et al. Effect of the addition of hop (infusion or powder) on the oxidative stability of lean lamb patties during storage. Small Rumin. Res. 2015; 125: 73–80. https://doi.org/10.1016/J.SMALLRUMRES.2015.02.008 . https://doi.org/10.1016/J.SMALLRUMRES.20... )
Bread and heterofermentative bread (sourdough)	Aqueous extract (boil, 1h)	Significant inhibition of: A . parasiticus , P . carneum , P . polonicum , P . paneum , P . chermesinum , A . niger , and P . roqueforti . (Nionelli et al. , 2018 Nionelli L, Pontonio E, Gobbetti M, Rizzello CG. Use of hop extract as antifungal ingredient for bread making and selection of autochthonous resistant starters for sourdough fermentation. Int J Food Microbiol. 2018; 266: 173–82. https://doi.org/10.1016/j.ijfoodmicro.2017.12.002 . https://doi.org/10.1016/j.ijfoodmicro.20... )
Food/breads	Solid-liquid extraction of hop seeds in 80:20 methanol:water	Polyphenols with inhibition of B. cereus, L. monocytogenes, E. faecalis, E. coli, Salmonella typhimurium and fungus Penicillium (Alonso-Esteban et al. , 2019 Alonso-Esteban JI, Pinela J, Barros L, Ćirić A, Soković M, Calhelha RC, et al. Phenolic composition and antioxidant, antimicrobial and cytotoxic properties of hop (Humulus lupulus L.) Seeds. Ind Crops Prod. 2019; 134: 154–9. https://doi.org/10.1016/j.indcrop.2019.04.001 . https://doi.org/10.1016/j.indcrop.2019.0... )
Chicken	Aqueous extract (boil 2g/L 30min)	Significant reduction (p < 0.05) in lactic bacteria count and Brochothrix thermosphacta without taste change (NIETO et al. , 2020)
Food	Ethyl acetate, ethanol or methanol extract from supercritical CO2 extraction residues	Moderate inhibition of Fusarium and Staphylococcus (Bartmańska et al. , ( 2018 Bartmańska A, Wałecka-Zacharska E, Tronina T, Popłoński J, Sordon S, Brzezowska E, et al. Antimicrobial Properties of Spent Hops Extracts, Flavonoids Isolated Therefrom, and Their Derivatives. Molecules. 2018; 23. https://doi.org/10.3390/MOLECULES23082059 . https://doi.org/10.3390/MOLECULES2308205... )).
Food and crops	Extraction of essential oils by Clevenger apparatus	Activity against Sitophilus granarius (PAVENTI et al. , 2020).
Food and crops	Xanthohumol extract	Activity against pests such as the Varroa destructor mite (DEGRANDI-HOFFMAN et al. , 2012) and various insects (AYDIN et al. , 2017)
Package	Chitosan silica film with 0.3% beta acids	Improvement in markers of oxidative and microbiological stability (TIAN et al. , 2021).

Application	Technology	Effect
Chicken	Addition of extract with 30 mg of beta acids / kg of food	Reduction of radical formation in the meat and increase of oxidative stability in general (Zawadzki et al. , ( 2018 Zawadzki A, Alloo C, Grossi AB, do Nascimento ESP, Almeida LC, Bogusz Junior S, et al. Effect of hop β-acids as dietary supplement for broiler chickens on meat composition and redox stability. Food Res Int. 2018; 105: 210–20. https://doi.org/10.1016/J.FOODRES.2017.10.072 . https://doi.org/10.1016/J.FOODRES.2017.1... ))
Chicken	Addition of 30-60mg of beta acids in microencapsulated form per kg of food.	Effect similar to zinc bacitracin as a performance enhancer by increasing the feed conversion ratio (Bortoluzzi et al. , ( 2015 Bortoluzzi C, Menten JFM, Pereira R, Fagundes NS, Napty GS, Pedroso AA, et al. Hops β-acids and zinc bacitracin affect the performance and intestinal microbiota of broilers challenged with Eimeria acervulina and Eimeria tenella. Anim Feed Sci Technol. 2015; 207: 181–9. https://doi.org/10.1016/J.ANIFEEDSCI.2015.06.006 . https://doi.org/10.1016/J.ANIFEEDSCI.201... ))
Swine	Addition of up to 360mg of microencapsulated beta acids per kg of food	Feed efficiency gain similar to colistin (Sbardella et al. , 2016) increase in protein content, decrease in fat content and increase in fat oxidative stability (Sbardella et al. , ( 2018 Sbardella M, Racanicci AMC, Gois FD, de Lima CB, Migotto DL, Costa LB, et al. Effects of dietary hop (Humulus lupulus L.) β-acids on quality attributes, composition and oxidative stability of pork meat. J Sci Food Agric. 2018; 98: 2385–92. https://doi.org/10.1002/JSFA.8730 . https://doi.org/10.1002/JSFA.8730... ))
Chicken	Additive containing extracted and modified hops.	Gut microbiota modulation, reduction of injury caused by C. perfringens and growth promoter similar to bacitricin (Vecchi et al. , 2021)
Swine	Pure beta acids obtained by extract purification with supercritical CO2	Activity against methicillin-resistant S. aureus in skin infections in vivo (Sleha et al. , ( 2021 Sleha R, Radochova V, Malis J, Mikyska A, Houska M, Krofta K, et al. Strong Antimicrobial and Healing Effects of Beta-Acids from Hops in Methicillin-Resistant Staphylococcus aureus-Infected External Wounds In Vivo. Antibiotics. 2021, Vol 10, Page 708 2021; 10: 708. https://doi.org/10.3390/ANTIBIOTICS10060708 . https://doi.org/10.3390/ANTIBIOTICS10060... )) and in vitro (Bogdanova et al. , 2018a)
Swine	Purified xanthohumol in intramuscular application 25mg/kg every 3 days.	Therapeutic effect in piglets infected with porcine reproductive and respiratory syndrome virus (Liu et al. , 2019b)
Ruminant	Methanolic extract with alpha and beta acids (49 and 38mg/g, respectively)	Rumen microbiota modulation and reduction in methane emission (Narvaez, Wang, Mcallister, 2013)
Ruminant	Beta acid extract by supercritical CO2 or tetra-hydro-iso-alpha-acids	Reduction of methane emission from Methanobrevibacter ruminantium comparable to metronidazole (Blaxland, Watkins, Baillie, ( 2021 Blaxland JA, Watkins AJ, Baillie LWJ. The Ability of Hop Extracts to Reduce the Methane Production of Methanobrevibacter ruminantium. Archaea. 2021; 2021. https://doi.org/10.1155/2021/5510063 . https://doi.org/10.1155/2021/5510063... ))

Application	Technology	Effect
Obesity and dyslipidemia	Isolated xanthohumol supplemented in food for 12 days at concentrations of 30 and 60mg/kg/day	Decreasing dose-dependent effect of weight gain, plasma LDL and IL-6 concentration in mice (Miranda et al. , 2016 Miranda CL, Elias VD, Hay JJ, Choi J, Reed RL, Stevens JF. Xanthohumol improves dysfunctional glucose and lipid metabolism in diet-induced obese C57BL/6J mice. Arch Biochem Biophys. 2016; 599: 22–30. https://doi.org/10.1016/j.abb.2016.03.008 . https://doi.org/10.1016/j.abb.2016.03.00... ) Decreased hepatic weight gain, plasma triglycerides and increased fecal excretion in mice (Yui, Kiyofuji, Osada, 2014 Yui K, Kiyofuji A, Osada K. Effects of xanthohumol-rich extract from the hop on fatty acid metabolism in rats fed a high-fat diet. J Oleo Sci. 2014; 63: 159–68. https://doi.org/10.5650/JOS.ESS13136 . https://doi.org/10.5650/JOS.ESS13136... )
Obesity and dyslipidemia	Isolated xanthohumol supplemented at 0.05% in an atherosclerotic diet	Reduction of cholesterol accumulation in atherosclerotic regions by inhibiting esterified cholesterol transfer protein in mice (Hirata et al. , 2012 Hirata H, Yimin, Segawa S, Ozaki M, Kobayashi N, Shigyo T, et al. Xanthohumol prevents atherosclerosis by reducing arterial cholesterol content via CETP and apolipoprotein E in CETP-transgenic mice. PLoS One. 2012; 7. https://doi.org/10.1371/JOURNAL.PONE.0049415 . https://doi.org/10.1371/JOURNAL.PONE.004... )
Obesity and dyslipidemia	Isolated xanthohumol	Inhibitor of adipogenesis and induction of lipolysis partially via AMP-activated protein kinase (Samuels, Shashidharamurthy, Rayalam, 2018 Samuels JS, Shashidharamurthy R, Rayalam S. Novel anti-obesity effects of beer hops compound xanthohumol: role of AMPK signaling pathway. Nutr Metab (Lond). 2018; 15. https://doi.org/10.1186/S12986-018-0277-8 . https://doi.org/10.1186/S12986-018-0277-... ).
Diabetes and dyslipidemia	Xanthohumol 10mg/L + 8-prenylnaringenin 10mg/L	Reduced fat accumulation, increased insulin sensitivity, glucose tolerance, and improved lipid profile over control (Costa et al. , 2017 Costa R, Rodrigues I, Guardão L, Rocha-Rodrigues S, Silva C, Magalhães J, et al. Xanthohumol and 8-prenylnaringenin ameliorate diabetic-related metabolic dysfunctions in mice. J Nutr Biochem. 2017; 45: 39–47. https://doi.org/10.1016/J.JNUTBIO.2017.03.006 . https://doi.org/10.1016/J.JNUTBIO.2017.0... )
Obesity and dyslipidemia	Extract derived from brewer's wort production residue (humolinones and iso-humolinones)	Secretion of the gastrointestinal hormone cholecystokinin in vitro (Yamazaki et al. , 2019) and fat reduction in a double-blind clinical study (Morimoto-Kobayashi et al. , 2016)
Obesity and type II diabetes	Tetra-iso-alpha-acids with different chemical substitutions supplemented in the diet	Reduction in weight gain, normalization of insulin sensitivity markers, increase in plasma concentration of anti-inflammatory cytokines and reduction in the concentration of pro-inflammatory cytokines in mice (Everard et al. , 2012)
Obesity and diabetes	Different fractions of aqueous extract of hops supplemented in the diet at 2 and 5%	Reduction in adipose tissue gain, adipocyte diameter and decreased glucose tolerance (Sumiyoshi, Kimura, 2013 Sumiyoshi M, Kimura Y. Hop (Humulus lupulus L.) extract inhibits obesity in mice fed a high-fat diet over the long term. Br J Nutr. 2013; 109: 162–72. https://doi.org/10.1017/S000711451200061X . https://doi.org/10.1017/S000711451200061... ).
Alzheimer's disease/neuroprotection	Isolated xanthohumol supplemented in food	Reduction of pro-inflammatory molecules in nervous tissue (Rancán et al. , 2017 Rancán L, Paredes SD, García I, Muñoz P, García C, López de Hontanar G, et al. Protective effect of xanthohumol against age-related brain damage. J Nutr Biochem. 2017; 49: 133–40. https://doi.org/10.1016/J.JNUTBIO.2017.07.011 . https://doi.org/10.1016/J.JNUTBIO.2017.0... )
Stroke/neuroprotection	Isolated xanthohumol in peritoneal application 0.2 and 0.4 mg/kg	Reduction of infarct size in induced ischemic stroke in treated groups (Yen et al. , 2012 Yen TL, Hsu CK, Lu WJ, Hsieh CY, Hsiao G, Chou DS, et al. Neuroprotective effects of xanthohumol, a prenylated flavonoid from hops (Humulus lupulus), in ischemic stroke of rats. J Agric Food Chem. 2012; 60: 1937–44. https://doi.org/10.1021/JF204909P . https://doi.org/10.1021/JF204909P... ).
Alzheimer's disease/neuroprotection	Xanthohumol in vitro	Reduction of oxidative stress, endoplasmic reticulum stress and chemoprotective effect against the development of Alzheimer's disease (Huang et al. , 2018).
Hepatoprotection	Xanthohumol supplemented in diet 1 mg/kg/day	Inflammation modulation and liver protector (Fernández-García et al. , 2019 Fernández-García C, Rancan L, Paredes SD, Montero C, de la Fuente M, Vara E, et al. Xanthohumol exerts protective effects in liver alterations associated with aging. Eur J Nutr. 2019; 58: 653–63. https://doi.org/10.1007/S00394-018-1657-6 . https://doi.org/10.1007/S00394-018-1657-... ).
Obesity-induced dementia	Iso-Alpha Acid Extract in diet	Reduction of neuronal loss and hippocampus atrophy (Ayabe et al. , 2018 Ayabe T, Ohya R, Kondo K, Ano Y. Iso-α-acids, bitter components of beer, prevent obesity-induced cognitive decline. Sci Rep. 2018; 8. https://doi.org/10.1038/S41598-018-23213-9 . https://doi.org/10.1038/S41598-018-23213... ) Reduced inflammation in the hippocampus and improved brain activity (Ano et al. , 2019 Ano Y, Yoshikawa M, Takaichi Y, Michikawa M, Uchida K, Nakayama H, et al. Iso-α-acids, bitter components in beer, suppress inflammatory responses and attenuate neural hyperactivation in the hippocampus. Front Pharmacol. 2019; 10: 81. https://doi.org/10.3389/FPHAR.2019.00081/BIBTEX . https://doi.org/10.3389/FPHAR.2019.00081... ).
Obesity-induced dementia	Extract derived from brewer's wort production residue (humolinones and iso-humolinones).	Improved verbal fluency and less mental fatigue than placebo in double-blind clinical trial (Fukuda et al. , 2020).
Anticancer	Isolated xanthohumol	Cytotoxicity and inhibition of proliferation in breast cancer cells (Kim; Lee; Moon, 2013). NF-kB inhibitor. Angiogenesis inhibition in pancreatic cancer (Saito et al. , 2018 Saito K, Matsuo Y, Imafuji H, Okubo T, Maeda Y, Sato T, et al. Xanthohumol inhibits angiogenesis by suppressing nuclear factor-κB activation in pancreatic cancer. Cancer Sci. 2018; 109: 132–40. https://doi.org/10.1111/CAS.13441 . https://doi.org/10.1111/CAS.13441... ).
Antiviral	Xanthohumol in peritoneal application	Reduction of liver damage and reduction of steatosis and fibrosis caused by hepatitis C virus (Yang et al. , 2013 Yang M, Li N, Li F, Zhu Q, Liu X, Han Q, et al. Xanthohumol, a main prenylated chalcone from hops, reduces liver damage and modulates oxidative reaction and apoptosis in hepatitis C virus infected Tupaia belangeri. Int Immunopharmacol. 2013; 16: 466–74. https://doi.org/10.1016/J.INTIMP.2013.04.029 . https://doi.org/10.1016/J.INTIMP.2013.04... )
Antiviral	Xanthohumol	Hepatitis C virus replication inhibition (Lou et al. , 2014 Lou S, Zheng YM, Liu SL, Qiu J, Han Q, Li N, et al. Inhibition of hepatitis C virus replication in vitro by xanthohumol, a natural product present in hops. Planta Med. 2014; 80: 171–6. https://doi.org/10.1055/S-0033-1360172 . https://doi.org/10.1055/S-0033-1360172... ) and protease inhibition related to coronavirus replication (Lin et al. , 2021 Lin Y, Zang R, Ma Y, Wang Z, Li L, Ding S, et al. Xanthohumol Is a Potent Pan-Inhibitor of Coronaviruses Targeting Main Protease. Int. J. Mol. Sci. 2021, Vol 22, Page 12134 2021; 22: 12134. https://doi.org/10.3390/IJMS222212134 . https://doi.org/10.3390/IJMS222212134... ).
Antibiotic	Xanthohumol	MIC and MIB similar to metronidazole in Clostridium difficile isolated from patients with nosocomial diarrhea (Cermak et al. , 2017 Cermak P, Olsovska J, Mikyska A, Dusek M, Kadleckova Z, Vanicek J, et al. Strong antimicrobial activity of xanthohumol and other derivatives from hops (Humulus lupulus L.) on gut anaerobic bacteria. APMIS. 2017; 125: 1033–8. https://doi.org/10.1111/apm.12747 . https://doi.org/10.1111/apm.12747... )
Antibiotic	Commercial extract of supercritical CO2, lupulone and xanthohumol.	Inhibition and reduction of Methicillin-resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci biofilm formation (Bogdanova et al. , 2018b).
Antibiotic	Hop alcoholic extract	Inhibition and reduction of biofilm formation in gram-positive bacteria related to antibiotic-resistant skin infections (Di Lodovico et al. , 2020 di Lodovico S, Menghini L, Ferrante C, Recchia E, Castro-Amorim J, Gameiro P, et al. Hop Extract: An Efficacious Antimicrobial and Anti-biofilm Agent Against Multidrug-Resistant Staphylococci Strains and Cutibacterium acnes. Front Microbiol. 2020; 11. https://doi.org/10.3389/fmicb.2020.01852 . https://doi.org/10.3389/fmicb.2020.01852... ).
Antibiotic	Hydroalcoholic extract of hop cones, leaves, stems and rhizomes further purified to concentrate xanthohumol, lupulone and deoxyxanthohumol	Antibiotic effect against Leishmania mexicana , Trypanosoma brucei and methicillin-resistant S. aureus (Bocquet et al. , 2019 Bocquet L, Sahpaz S, Bonneau N, Beaufay C, Mahieux S, Samaillie J, et al. Phenolic Compounds from Humulus lupulus as Natural Antimicrobial Products: New Weapons in the Fight against Methicillin Resistant Staphylococcus aureus, Leishmania mexicana and Trypanosoma brucei Strains. Molecules. 2019, Vol 24, Page 1024 2019; 24: 1024. https://doi.org/10.3390/MOLECULES24061024 . https://doi.org/10.3390/MOLECULES2406102... ).
Antioxidant	Extrato feito por partição hexano e metanol.	Fraction of hexane rich in alpha and beta acids inhibited lipid peroxidation (Kontek et al. , 2021 Kontek B, Jedrejek D, Oleszek W, Olas B. Antiradical and antioxidant activity in vitro of hops-derived extracts rich in bitter acids and xanthohumol. Ind Crops Prod. 2021; 161: 113208. https://doi.org/10.1016/j.indcrop.2020.113208 . https://doi.org/10.1016/j.indcrop.2020.1... ).
Control of disease vectors	Essential oil extract	Toxic for mosquitoes and molluscs vectors of diseases (Bedini et al. , 2016).

[1] *Correspondence: R. S. Rosa. E-mail: raul.rosa@usp.br .

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Hop extracts and their utilizations: perspectives based on the last 10 years of research

Abstract