Hop acids, a family of bitter compounds derived from the hop plant (Humulus lupulus), have been reported to exert a wide range of effects, both in vitro and in vivo. They exhibit potential anticancer activity by inhibiting cell proliferation and angiogenesis, by inducing apoptosis, and by increasing the expression of cytochrome P450 detoxification enzymes. Furthermore, hop bitter acids are effective against inflammatory and metabolic disorders, which makes them challenging candidates for the treatment of diabetes mellitus, cardiovascular diseases, and metabolic syndrome. This review summarizes the current knowledge on hop bitter acids, including both phytochemical aspects, as well as the biological and pharmacological properties of these compounds.

Hop (Humulus lupulus L.) is an essential ingredient of beer, where it provides the typical bitter taste, but is also applied in traditional folk medicine for sedative and antibacterial purposes. In this study, we demonstrate and compare the anti-inflammatory effect of various classes of hop bitter acids (HBA), including alpha-acids (AA), beta-acids (BA), and iso-alpha-acids (IAA), in fibroblasts, which are important players in the inflammatory response. All three studied classes of HBA blocked the tumor necrosis factor alpha (TNF)-induced production of the cytokine IL6, and inhibited the transactivation of the pro-inflammatory transcription factors nuclear factor kappa B (NF-kappaB), activator protein-1 (AP-1), and cAMP-response element-binding protein (CREB). In this respect, the six-membered ring compounds AA and BA showed equal potency, whereas the five-membered ring compounds, IAA, were effective only when used at higher concentrations. Furthermore, with regard to the mechanism of NF-kappaB suppression, we excluded a possible role for glucocorticoid receptor alpha (GRalpha), peroxisome proliferators-activated receptor alpha/gamma (PPARalpha or PPARgamma), nuclear receptors (NRs) that are also known to inhibit inflammation by directly interfering with the activity of pro-inflammatory transcription factors. Interestingly, combining hop acids and selective agonists for GRalpha, PPARalpha, or PPARgamma resulted in additive inhibition of NF-kappaB activity after TNF treatment, which may open up new avenues for combinatorial anti-inflammatory strategies with fewer side effects. Finally, systemic administration of HBA efficiently inhibited acute local inflammation in vivo.

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Nuclear magnetic resonance ͑NMR͒ investigations of methyl tunneling in 2,5-dimethyl-1,3,4-thiadiazole are reported. The tunneling frequency ( t ϭ 3.39 MHz͒ was obtained using low field NMR spectroscopy. By means of rapid field cycling irradiation and relaxation measurements the probabilities of the absorption transitions, responsible for the spectral lines in the low field NMR spectra, can be quantified. The results obtained agree well with the calculated probabilities of rf induced transitions between the eigenstates of a methyl rotor with t ϭ 3.39 MHz. Measurements of the temperature dependence of t , the spin conversion time con and an analysis of the proton spin lattice relaxation time T 1 , the latter two revealing the correlation time c , enabled the study of the methyl group dynamics over a temperature range encompassing both the quantum mechanical and the classical regimes. The dynamical data can be explained well with a threefold hindering barrier of height V 3 /k B ϭ 1175 K and are compared with existing theoretical models.

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