Comparison of anti-atopic dermatitis activities between DHMEQ and tacrolimus ointments in mouse model without stratum corneum.

This study is aimed to further investigate the anti-atopic dermatitis (AD) activities of dehydroxymethylepoxyquinomicin (DHMEQ) ointment and compare its effect with that of tacrolimus ointment based on the previous study that DHMEQ improves AD-like lesions. AD were induced by 2,4-dinitroclilorobenzene/oxazolone (DNCB/OX) repeatedly on the ears of BABL/C mice while medical tape was additionally used to disrupt stratum corneum in order to exacerbate the lesions. The mice were randomly divided into groups, which are normal, vehicle, DHMEQ (0.1%) and tacrolimus (0.1%). Those in the last two groups were externally applied with DHMEQ ointment and tacrolimus ointment, respectively. The results showed that both of them significantly improved dermatitis symptoms of DNCB/OX-induced AD-like lesions, such as redness, itching, weeping, scaling and thickening of the skin, while reducing epidermis thickness, dermis thickness and the number of mast cells as well, which were examined histopathologically. In contrast with DHMEQ, tacrolimus led to a significant decrease in body weight after long-term application. Both DHMEQ and tacrolimus suppress DNCB-induced increase of serum total IgE and attenuate expression of inflammatory factors IL-4, IL-6, IL-13, IL-1ß and interferon (IFN)-γ in the disrupted ear tissues. On the other hand, the mice applied with tacrolimus became obviously irritable, jumping up and down, and inflammatory exudation on the lesioned-skin surface of the mice was remarkably observed. Contrary to the side effects made by tacrolimus, DHMEQ didn't cause any adverse stimulus response. As a conclusion, DHMEQ is safer, milder and more suitable for long-term use than tacrolimus for the treatment of AD-like lesions.

Dehydroxymethylepoxyquinomicin suppresses atopic dermatitis-like lesions in a stratum corneum-removed murine model through NF-κB inhibition.

Background: Dehydroxymethylepoxyquinomicin (DHMEQ) is a specific and potent inhibitor of nuclear factor-kappa B (NF-κB) and has been shown to possess promising potential as an anti-inflammation including anti-atopic dermatitis (AD)-like skin lesions. Objective: To further evaluate the activity of DHMEQ in vivo modified AD-like lesion model in BALB/c mice and in vitro AD-like lesion cell model in human keratinocytes. Materials and methods: In this study, in vivo modified AD-like lesion model in BALB/c mice was chronically induced by the repetitive and alternative application of 2,4-dinitrochlorobenzene (DNCB) and oxazolone (OX) on ears, and stratum corneum of the ear skin was additionally stripped off with surgical tapes before each challenge with DNCB/OX. Moreover, in vitro AD-like lesion cell model in human keratinocytes (HaCaT) achieved by stimulating HaCaT cells with tumor necrosis factor (TNF)-α plus interferon (IFN)-γ was used to investigate mechanisms of the action. Results: The lesions derived from the stratum corneum-removed AD-like lesion model reaches to peak as well as DHMEQ arrives to its efficacy a week earlier than the data previously obtained from the common AD-like lesion model. Results showed that the drug reduced the ear thickness, epidermal thickness, mast cell infiltration, and gene expressions of interleukin (IL)-4, IL-13, and interferon (IFN)-γ in ear tissues. It significantly inhibited the expression of cytokines IL-6 and IL-1ß, chemokines thymus and activation-regulated chemokine (TARC)/CCL17, and macrophage-derived chemokine (MDC)/CCL22 in the stimulated HaCaT cells. Discussion and conclusion: This study indicated that the action of DHMEQ's anti-AD like lesions might be related to its inhibition on NF-κB.