Cardamonin Inhibits Oxazolone-Induced Atopic Dermatitis by the Induction of NRF2 and the Inhibition of Th2 Cytokine Production

Abstract

The skin is constantly exposed to various types of chemical stresses that challenge the immune cells, leading to the activation of T cell-mediated hypersensitivity reactions including atopic dermatitis. Previous studies have demonstrated that a variety of natural compounds are effective against development of atopic dermatitis by modulating immune responses. Cardamonin is a natural compound abundantly found in cardamom spices and many other medicinal plant species. In the present study, we attempted to examine whether cardamonin could inhibit oxazolone-induced atopic dermatitis in vivo. Our results show that topical application of cardamonin onto the ear of mice suppressed oxazolone-induced inflammation in the ear and hyperplasia in the spleen. Cardamonin also inhibited oxazolone-induced destruction of connective tissues and subsequent infiltration of mast cells into the skin. In addition, we found that the production of Th2 cytokines is negatively regulated by NRF2, and the induction of NRF2 by cardamonin contributed to suppressing oxazolone-induced Th2 cytokine production and oxidative damages in vivo. Together, our results demonstrate that cardamonin is a promising natural compound, which might be effective for treatment of atopic dermatitis.

Aryl hydrocarbon receptor/nuclear factor E2‐related factor 2 (AHR/NRF2) signalling: A novel therapeutic target for atopic dermatitis

“…65 NRF2 activation exhibits suppressive effects on Th2 cytokines (IL-13, IL-33 and IL-1β) in mouse fibroblasts, but the mechanism is not fully understood. 66 Rectifying this imbalance in the Th2 and AHR axis can rescue epidermal barrier function through AHR-mediated EDC activation and have therapeutic potential for AD. 32,36…”

“…Asthma, a closely related atopic disease to AD, was shown to be attenuated by AHR activation via polarization macrophages to an M2 anti‐inflammatory phenotype in a mouse model 65 . NRF2 activation exhibits suppressive effects on Th2 cytokines (IL‐13, IL‐33 and IL‐1β) in mouse fibroblasts, but the mechanism is not fully understood 66 . Rectifying this imbalance in the Th2 and AHR axis can rescue epidermal barrier function through AHR‐mediated EDC activation and have therapeutic potential for AD 32,36 …”

Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery

“…Cardamonin (CAR), a flavone exclusively found in Alpinia plant, has demonstrated potential in reducing oxidative stress via regulating Nrf2 signaling. It is noteworthy that CAR activates Nrf2 signaling that is of importance in reducing Th2 cytokine generation and preventing dermatitis [103]. In vivo experiment on mice demonstrates that CAR alleviates myocardial contractile dysfunction via enhancing Nrf2 expression [104].…”

The Role of KEAP1-NRF2 System in Atopic Dermatitis and Psoriasis

“…A naturally occurring flavone chrysin derivative inhibited the NF-κB and JAK2/STAT1 signaling pathways in LPS-activated macrophages [ 72 ]. Cardamonin, a natural compound abundantly found in cardamom species, inhibited Th2 cytokines production in mouse AD skin [ 73 ].…”