Medical Attributes of Humulus lupulus - Hops

By Michelle Wakeley and Michael Ryan
Wilkes University, Wilkes-Barre, PA

July, 2011

Humulus lupulus (common hop) is a perennial herbaceous vine of the Cannabaceae (hemp family).  The species is native to Europe, Asia, and North America (Chadwick et al. 2006; Al-Mamun et al. 2009).  Humulus lupulus dies back to a rhizome in the winter and generates shoots each spring.  Plants live between 10 and 20 years (Duke 1998).  Each summer, the plants produce resinous, cone-like strobiles with actinomorphic, light green, apetalous, wind pollinated flowers with a short calyx (Gleason and Cronquist 1963; Duke 1998).  Hops is currently cultivated largely in Japan, as well as throughout the northern hemisphere.  However, its sensitive photoperiod prohibits growth in the southern hemisphere (Al-Mamun et al. 2009).

Historically, the strobiles of H. lupulus have been used by the beer industry to add bitter flavor to the beverage thanks to concentrations of phenolic flavonoids (Overk et al. 2005, Al-Mumun et al. 2009).  The strobiles have also been used as a preservative in sausages by the Germans (Duke 1998).


Hops has been used as an herbal remedy for centuries to treat numerous disorders.  Historically, it has been used for the treatment of anxiety and insomnia in both the U.S. and Europe (Chadwick 2006), and is reputed to have an antimicrobial ability similar to other species in the Cannabaceae (Duke 1998).  The strobiles of the hops plant have been used since 1953 as a potential estrogen replacement (Overk 2005).  Further, the extracts from H. lupulus have emerged as major constituents of commercial breast enhancement preparations (Nikolic 2007).   In addition to their traditional uses, H. lupulus has been shown within the past decade to be effective in suppressing human cancer cell growth, especially in the case of colon cancers (Chung 2009).


The medicinal uses of the hops plant result from the presence of a handful of chemicals found throughout the plant.  The strobiles of the hops plant possess a powerful phytoestrogen, 8-prenylnarignenin (PN-8) (Overk et al. 2005, Bowe et al. 2008).  The medicinally active chemical isoxanthohumol is also found in hops (Overk et al. 2008).  The bitter flavor used in beer making results from humulone and lupulone production, as well as xanthohumol (Al-Mumun et al. 2009, Lee et al. 2011). H. lupulus has also recently been implicated as a major producer of oligomeric mixtures of proanthocyanidins, and additionally contain xanthohumol and proanthocyanidins (Chung et al. 2009, Deeb et al. 2010). 


PN-8 is perhaps the most heavily investigated medicinally significant component in H. lupulus (Overk et al. 2005).  This compound has been largely explored as an alternative to hormone therapy as a treatment for menopause symptoms (Overk et. al. 2008).  PN-8 was shown to associate with estrogen receptors in a variety of estrogenic assays (Overk et al. 2005).  In a rat model, it reduced simulated hot flashes (Bowe et al. 2006), but had a potentially adverse estrogenic effect by increasing uterus weight (Overk et al. 2008).  Interestingly, the results of 8-PN on uterus weight were not reproducible when whole H. lupulus extract was administered instead of the purified compound alone (Overk et al. 2008). 


H. lupulus is also shown promise as an anti-inflammatory.  A combination in vitro / in vivo study using mice with collagen induced arthritis fed Rho iso-alpha acids (RIAA) harvested from hops plants decreased the joint swelling and arthritis index by selectively inhibiting the NF-kappa-B pathway (a protein complex found in nearly all types of cells which regulates immune response to stress), while not affecting phosphorylation pathways including ERK1/2 (extracellular signal regulated kinases, common MAP kinases), p38 (a class of phosphorylating enzymes) and JNK (c-Jun N-terminal kinases, common MAP kinases) (Konda et al. 2009). Additionally, a study of the chalcone derivative xanthohumol in mouse cells proved it to be effective in inhibiting the production of inflammatory mediators acting on microglial BV2 cells using NRF2 (a protein complex similar to NF-kappa-B) signaling (Lee et al. 2011).


Regarding recent claims that hops effectively treats cancer cells, in vitro studies of the common hops constituents xanthohumol and proanthocyanidins both show anti-carcinogenic properties.  Xanthohumol was shown to promote apoptosis in prostate cancer cells of humans (Deeb et al. 2010), while the proanthocyanidins derived from H. lupulus decrease the viability of cancer cells by mediating formation of H2O2 within the cells, and inducing changes in a cell's actin cytoskeleton (Chung et al. 2009).  Since cancer cells proliferate more frequently than healthy cells, an inability to produce the spindle apparatus inhibits the growth of tumors, but has minimal effect on healthy tissue.


Ethanolic and CO2 extracts of H. lupulus have been shown in vivo to have a sedating effect.  In tests of CO2 extracts of hops containing alpha-acids, mice experienced an increase in phenobarbital induced sleeping time and a decrease in core body temperature without having an anxiolytic effect or inducing a loss of motor activity (Zanoli et al. 2005, Schiller 2006).


A few adverse reactions have been noted resulting from the use of compounds isolated from hops.  One such concern is that H. lupulus can cause drug-drug interactions with the numerous drugs metabolized by Pregnane X receptor (a nuclear receptor which senses foreign toxic substances, then up regulate necessary proteins for detoxification) (Teocico et al. 2008).  Further, the effect of PN-8 on increased uterus weight is a major concern if it is to be a consistently used alternative to hormone replacement therapy (Overk et al. 2008).


In general, H. lupulus and its constituents show promise in a variety of different medical applications.  Xanthohumol is an anti-inflammatory and anti-carcinogen.  PN-8 is, to quote Zanoli (2008), " of the most potent phytoestrogens isolated until now,", and is a promising treatment for menopause symptoms, and the extracts have even been shown to work as a light sedative.  While the mechanisms by which hops acts in the body have a great deal more to be explored, this simple plant to treat some of the great challenges in medicine today.

Literature Cited

Al-Mamun M., K. Goto, S. Chiba, & H. Sano. 2009. Responses of plasma acetate metabolism to hop (Humulus lupulus L.) in sheep. Int J Biol Sci 5(3):287-92.


Bowe J., X.F. Li, J. Kinsey-Jones, et al. 2006. The hop phytoestrogen, 8-prenylnaringenin, reverses the ovariectomy-induced rise in skin temperature in an animal model of menopausal hot flushes. J Endocrinol 191(2):399-405.


Chadwick L.R., G.F. Pauli, & N.R. Farnsworth. 2006. The pharmacognosy of Humulus lupulus L. (hops) with an emphasis on estrogenic properties. Phytomedicine 13(1-2):119-31.


Chung W. G., C.L. Miranda, J.F. Stevens, & C.S. Maier. 2009. Hop proanthocyanidins induce apoptosis, protein carbonylation, and cytoskeleton disorganization in human colorectal adenocarcinoma cells via reactive oxygen species. Food Chem Toxicol 47(4):827-836.


Deeb, D., X. Gao, H. Jiang, A.S. Arbab, S.A. Dulchavsky, & S.C. Gautam. 2010. Growth inhibitory and apoptosis-inducing effects of xanthohumol, a prenylated chalone present in hops, in human prostate cancer cells. Anticancer Research 30(9):3333-3339.


Duke, J. A. 1998. Humulus lupulus L..  Purdue University Center for New Crops and Plants Products.


Gleason, H. A. & A. Cronquist. 1963. Manual of Vascular Plants of Northeastern United States and Adjacent Canada. D. Van Nostrand Company, New York. p. 255.


Konda, V.R., A. Desai, G. Darland, J.S. Bland, & M.L. Tripp. 2009. Rho iso-alpha acids from hops inhibit the GSK-3/NF-kappaB pathway and reduce inflammatory markers associated with bone and cartilage degradation. J Inflamm (Lond) 6:26.


Lee, I.S., J. Lim, J. Gal, J.C. Kang, H.J. Kim, B.Y. Kang, & H. J. Choi.  2011. Anti-inflammatory activity of xanthohumol involves heme oxygenase-1 induction via NRF2-ARE signaling in microglial BV2 cells. Neurochemistry International 58(2):153-160.


Nikolic, D., Y. Li, L.R. Chadwick, & R.B. van Breemen. 2006. In vitro studies of intestinal permeability and hepatic and intestinal metabolism of 8-prenylnaringenin, a potent phytoestrogen from hops (Humulus lupulus L.). Pharm Res 23(5):864-872.


Overk, C.R., J. Guo, L. R. Chadwick, D.D. Lantvit, A. Minassi, G. Appendino, S.N. Chen, D.C. Lankin, N. R. Farnsworth, G.F. Pauli et al. 2008. In vivo estrogenic comparisons of Trifolium pratense (red clover), Humulus lupulus (hops), and the pure compounds isoxanthohumol and 8-prenylnaringenin. Chem Biol Interact 176(1):30-9.


Overk, C.R., P. Yao, L.R. Chadwick et al. 2005. Comparison of the in vitro estrogenic activities of compounds from hops (Humulus lupulus) and red clover (Trifolium pratense). J Agric Food Chem 53(16):6246-6253.


Schiller, H., A. Forster, C. Vonhoff, M. Hegger, A. Biller, H. Winterhoff. 2006. Sedating effects of Humulus lupulus L. extracts. Phytomedicine 13: 535-41.


Teotico D.G., J.J. Bischof, L. Peng, S.A. Kliewer, & M.R. Redinbo. 2008. Structural basis of human pregnane X receptor activation by the hops constituent colupulone. Mol Pharmacol 74(6):1512-20.


Zanoli P., M. Rivasi, M. Zavatti, F. Brusiani, & M. Baraldi. 2005. New insight in the neuropharmacological activity of Humulus lupulus L. J Ethnopharmacol. 102: 102-6.


Zanoli P., & M. Zavatti.  2008. Pharmacognostic and pharmacological profile of Humulus lupulus L. J Ethnopharmacol. 116: 383-96.

This paper was developed as part of the BIO 368 - Medical Botany course offered at Wilkes University during the summer of 1999. Course instructor was Kenneth M. Klemow, Ph.D. ( The information contained herein is based on published sources, and is made available for academic purposes only. No warrantees, expressed or implied, are made about the medical usefulness or dangers associated with the plant species in question.

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