(R)-Humulone

Names

[ Name ]:
(R)-Humulone

[Synonym ]:
a-Bitter Acid
(R)-3,5,6-Trihydroxy-2-isovaleryl-4,6-bis-(3-methyl-but-2-enyl)-cyclohexa-2,4-dienon
2,4-Cyclohexadien-1-one, 3,5,6-trihydroxy-2-isovaleryl-4,6-bis(3-methyl-2-butenyl)-, (R)-(-)-
3,5,6β-Trihydroxy-2-isovaleryl-4,6α-bis(3-methyl-2-butenyl)-2,4-cyclohexadienon
Humulon
(6R)-3,5,6-trihydroxy-2-isovaleryl-4,6-bis(3-methylbut-2-enyl)cyclohexa-2,4-dienone
a-Lupulic Acid
2,4-Cyclohexadien-1-one, 3,5,6-trihydroxy-4,6-bis(3-methyl-2-buten-1-yl)-2-(3-methyl-1-oxobutyl)-, (6R)-
2,4-Cyclohexadien-1-one, 3,5,6-trihydroxy-4,6-bis(3-methyl-2-butenyl)-2-(3-methyl-1-oxobutyl)-, (R)-
(R)-2.3.6-Trihydroxy-1.3-bis-(3-methyl-buten-(2)-yl)-5-isovaleryl-cyclohexadien-(1.5)-on-(4)
α-Lupulic acid
(R)-3,5,6-trihydroxy-2-isovaleryl-4,6-bis-(3-methyl-but-2-enyl)-cyclohexa-2,4-dienone
(6R)-3,5,6-Trihydroxy-2-(3-methylbutanoyl)-4,6-bis(3-methyl-2-buten-1-yl)-2,4-cyclohexadien-1-one
Humulone,mixture of homologues
|A-Lupulic acid
2',3'-Dihydro-3'β,4',6'-trihydroxy-3'α,5'-bis(3-methyl-2-butenyl)-2'-oxoisovalerophenon
(R)-3,5,6-Trihydroxy-4,6-bis(3-methyl-2-butenyl)-2-(3-methyl-1-oxobutyl)-2,4-cyclohexadien-1-one
(6R)-3,5,6-Trihydroxy-2-(3-methylbutanoyl)-4,6-bis(3-methylbut-2-en-1-yl)cyclohexa-2,4-dien-1-one
|A-Bitter acid
Humulone
humulone, (R)-
α-Bitter acid

Biological Activity

[Description]:

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].

[Related Catalog]:

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Immunology/Inflammation >> COX

Signaling Pathways >> Membrane Transporter/Ion Channel >> GABA Receptor

Signaling Pathways >> Neuronal Signaling >> GABA Receptor

[Target]

COX-2

[In Vitro]

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].

[In Vivo]

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]. Animal Model: Male BALB/cAnNRj mice (9-11 weeks of age)[2] Dosage: 10 or 20 mg/kg Administration: IP; pre-treatment before sodium pentobarbital (35 mg/kg; i.p.) and ethanol (3.5 g/kg) Result: Significantly decreased the latency and prolonged the duration of sleep induced by pentobarbital at 20 mg/kg dose. These effects were not observed at a lower dose of 10 mg/kg. Showed no effect on the onset of sleep induced by ethanol, but significantly increased sleep duration dose-dependently.

[References]

[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.

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
571.4±50.0 °C at 760 mmHg

[ Melting Point ]:
65-66.5℃

[ Molecular Formula ]:
C₂₁H₃₀O₅

[ Molecular Weight ]:
362.460

[ Flash Point ]:
313.4±26.6 °C

[ Exact Mass ]:
362.209320

[ PSA ]:
94.83000

[ LogP ]:
5.14

[ Vapour Pressure ]:
0.0±3.6 mmHg at 25°C

[ Index of Refraction ]:
1.558

Safety Information

[ Hazard Codes ]:
Xi

[ WGK Germany ]:
3

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Related Compounds

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