Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 193, Issue -, Pages 1-8Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2022.09.028
Keywords
Anti -inflammation; Arachidonate 5-lipoxygenase; Leukotriene B 4; Malabaricone C; Psoriasis
Funding
- JSPS KAKENHI
- Japan Food Chemical Research Foundation (Osaka, Japan)
- Mitsui Sumitomo Insurance Welfare Foundation (Tokyo, Japan)
- Kieikai Research Foundation (Tokyo, Japan)
- [18K11134]
- [26750049]
Ask authors/readers for more resources
In this study, it was found that malabaricone C, a component of nutmeg, strongly inhibited the activity of 5-lipoxygenase, an enzyme involved in leukotriene biosynthesis. Furthermore, malabaricone C was shown to ameliorate psoriasis-like skin inflammation by decreasing the level of leukotriene B4.
As pro-inflammatory lipid mediators, leukotrienes have pathophysiological activities in several inflammatory diseases, including psoriasis. In the biosynthesis of leukotrienes from arachidonic acid, 5-lipoxygenase catalyzes the first two steps. In the present study, we showed that nutmeg (Myristica fragrans) strongly inhibited the catalytic activity of 5-lipoxygenase. To characterize the bioactive component(s) of nutmeg, we performed 5-lipoxygenase inhibitory activity-guided fractionation of aqueous ethanol extract of nutmeg, resulting in the isolation of malabaricone C having antioxidant activity. Malabaricone C exhibited potent competitive inhibition of 5lipoxygenase with an IC50 value of 0.2 mu M. In mice with imiquimod-induced psoriasis-like skin lesions, topical application of 2 mM malabaricone C significantly ameliorated hyperplasia and inflammatory cell infiltration, and suppressed the expression of the psoriasis-associated genes S100a9, Krt1, Il17a, and Il22. Lipid metabolome analysis of these psoriasis-like skin lesions showed that malabaricone C markedly decreased the level of leukotriene B4 but did not significantly increase the other pro-inflammatory lipid mediators. These findings suggest that malabaricone C decreases LTB4 by the 5-lipoxygenase inhibition and ameliorates the symptoms of psoriasis-like skin inflammation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available