Humulone (α-Lupulic acid), a prenylated phloroglucinol derivative, is a potent cyclooxygenase-2 (COX-2) inhibitor. Humulone acts as a positive modulator of GABAA receptor at low micromolar concentrations. Humulone is an inhibitor of bone resorption. Humulone possesses antioxidant, anti-angiogenic and apoptosis-inducing properties[1][2][3].
Humulone (0.1, 1, 10, 100, 1000, 10000 nM; for 12 h) with with 10 ng/ml TNFα dose-dependently decreases the amount of released PGE2 with an IC50 of about 30 nM in MC3T3-E1 cells. Humulone reduces cyclooxygenase activity of the TNFK-treated cells[1]. Humulone (0.1-10000 nM; for 12 h) suppresses the TNFα-induced increase of cyclooxygenase-2 mRNA[1]. Humulone hardly affects the cyclooxygenase-1 activity below 10 μM, whereas inhibits the cyclooxygenase-2 activity with an IC50 of about 1.6 μM in MC3T3-E1 cells[1].
Humulone (10 or 20 mg/kg; IP; single dose) shortens sleep onset and increases the duration of sleep induced by pentobarbital and decreases the spontaneous locomotion in open field at 20 mg/kg[2]. Humulone (10 μmol; applied topically to the dorsal shaved area) pre-treatment significantly inhibited TPA (10 nmol)-induced COX-2 expression in Female ICR mice (6-7 weeks of age) skin[3]. Humulone (1, 10 μmol; applied topical; pre-treatment 30 min) suppresses TPA-induced NF-κB DNA binding. Humulone attenuates TPA-stimulated nuclear translocation of p65 and p50 subunit proteins of NF-κB[3].
[1]. K Yamamoto, et al. Suppression of cyclooxygenase-2 gene transcription by humulon of beer hop extract studied with reference to glucocorticoid. FEBS Lett. 2000 Jan 14;465(2-3):103-6.
[2]. Ali Y Benkherouf, et al. Humulone Modulation of GABA A Receptors and Its Role in Hops Sleep-Promoting Activity. Front Neurosci. 2020 Oct 14;14:594708.
[3]. Jung-Chul Lee, et al. Humulone inhibits phorbol ester-induced COX-2 expression in mouse skin by blocking activation of NF-kappaB and AP-1: IkappaB kinase and c-Jun-N-terminal kinase as respective potential upstream targets. Carcinogenesis. 2007 Jul;28(7):1491-8.