We previously reported that hexahydro-beta-
acids (HBAs), reduced derivatives of beta-
acids (BA) from hop (Humulus lupulus L.), displayed more potent anti-inflammatory activity than BA in
lipopolysaccharide-stimulated murine macrophages. In this study, we investigated the effects and underlying molecular mechanisms of hexahydro-β-
acids (HBAs) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated mouse skin
inflammation and in the two-stage
carcinogenesis model. Female ICR mice pretreated with HBA at 1 and 10 μg significantly reduced ear
edema, epidermal
hyperplasia, and infiltration of inflammatory cells caused by TPA. Molecular analysis exhibited that HBA suppressed iNOS, COX-2, and
ornithine decarboxylase (ODC)
protein and gene expression through interfering with
mitogen-activated protein kinases (MAPKs) and phosphatidylinositiol 3-kinase (PI3K)/Akt signaling as well as the activation of
transcription factor NF-κB. Furthermore, application of HBA (1 and 10 μg) prior to each TPA treatment (17.2 ± 0.9
tumors/mouse) resulted in the significant reduction of
tumor multiplicity (5.1 ± 1.2, P < 0.01 and 2.3 ± 1.2, P < 0.001, respectively) in 7,12-dimethyl-benzanthracene (DMBA)-initiated mouse skin. The
tumor incidence was significantly lowered to 75% (P < 0.05) and 58.7% (P < 0.01) by HBA pretreatment, respectively, and significantly reduced the
tumor weight (0.34 ± 0.14 g, P < 0.01 and 0.09 ± 0.10 g, P < 0.001, respectively) as compared to DMBA/TPA-induced
tumors (0.76 ± 0.04 g).