Mi Hwa Han

Inhibition of atopic dermatitis by topical application of silymarin in NC/Nga mice.

Silymarin has been known to inhibit chemical-induced irritant contact dermatitis. In the present study, we report that topical application of silymarin suppresses dust mite extract (DPE)-induced atopic dermatitis (AD) in NC/Nga mice. Repeated topical application of ears with DPE caused AD-like skin lesions in NC/Nga mice. However, silymarin reduced AD-like skin lesions in these mice, resulting in decreased ear swelling and leukocyte infiltration into the ear. Moreover, our results showed that mast cell infiltration into the ear was suppressed by silymarin treatment in DPE-treated NC/Nga mice. Silymarin also reduced plasma level of IL-4 and IgE in these mice. Further study demonstrated that the mRNA expression of IL-4 was increased and that of IFN-gamma was decreased by DPE treatment in the ears of NC/Nga mice. However, DPE-induced changes in IL-4 and IFN-gamma mRNA expression were reversed by silymarin. DPE-induced increase in TNF-alpha mRNA expression was also suppressed by silymarin treatment. The results presented in this report suggest that silymarin might be beneficial for the treatment of AD.

Inhibition of atopic dermatitis-like skin lesions by topical application of a novel ceramide derivative, K6PC-9p, in NC/Nga mice.

Abstract:  Atopic dermatitis (AD) is a chronic inflammatory skin disease that commonly begins in childhood. K6PC‐9p (N‐(Ethyl dihydrogenphosphate)‐2‐hexyl‐3‐oxo‐decanamide) is a synthetic ceramide derivative of PC‐9S (N‐Ethanol‐2‐mirystyl‐3‐oxo‐staramide), which was known to be effective in atopic patients. In this study, we examined the effect of topical application of K6PC‐9p on skin inflammation and AD‐like skin lesions in mouse models. K6PC‐9p dose‐dependently inhibited phorbol ester‐induced increase in ear thickness in BALB/c mice. Moreover, topical application of K6PC‐9p suppressed dust mite extract‐induced AD‐like skin lesions in NC/Nga mice. Histopathological analysis revealed that both ear swelling and leucocyte infiltration were suppressed by K6PC‐9p treatment. K6PC‐9p also suppressed IL‐4 and TNF‐α expression in the ears and mast cell infiltration into the ears in NC/Nga mice. Further study demonstrated that K6PC‐9p inhibited ConA‐induced IL‐4 secretion and LPS‐induced macrophage activation. Taken together, our results showed that topical application of K6PC‐9p exerts beneficial effects in animal model of skin inflammation and AD, suggesting that K6PC‐9p might be a promising topical agent for the treatment of inflammatory skin diseases.

Antiinflammatory activity of methanol extract isolated from stem bark of Magnolia kobus

The present study reports the antiinflammatory activity of a methanol extract isolated from the stem bark of Magnolia kobus (MK). MK potently inhibited lipopolysaccharide (LPS)‐induced production of nitric oxide and interleukin‐1β (IL‐1β) in RAW 264.7 cells, a murine macrophage‐like cell line. The secretion of tumor necrosis factor‐α (TNF‐α) was also suppressed in LPS‐stimulated RAW 264.7 cells although the magnitude of inhibition was weaker than that of nitric oxide and IL‐1β. The mRNA expressions of inducible nitric oxide synthase (iNOS), IL‐1β and TNF‐α were also suppressed by MK in LPS‐stimulated RAW 264.7 cells. Further study demonstrated that LPS‐induced DNA binding of AP‐1 and phosphorylation of c‐jun N‐terminal kinase (JNK) were inhibited by MK treatment in RAW 264.7 cells, whereas phosphorylation of p38 mitogen‐activated protein kinase was unaffected. Moreover, topical application of MK suppressed ear swelling in 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced skin inflammation model. Collectively, these results suggest that MK exerts antiinflammatory effects in vitro and in vivo and this might be mediated, at least in part, by blocking AP‐1 and JNK activation. Copyright

Inhibition of skin inflammation and atopic dermatitis by topical application of a novel ceramide derivative, K112PC-5, in mice

PC-9S (N-Ethanol-2-mirystyl-3-oxo-stearamide) is a synthetic ceramide and has been known to be effective in atopic and psoriatic patients. K112PC-5 (2-Acetyl-N-(1,3-dihydroxyisopropyl)-tetradecanamide) is a novel ceramide derivative of PC-9S. In the present study, we examined the effect of K112PC-5 on macrophage and T lymphocyte function in primary macrophages and splenocytes, respectively, as well as the effect of topical application of K112PC-5 on skin inflammation and atopic dermatitis (AD) in mouse models. K112PC-5 inhibited lipopolysaccharide-induced nitrite generation in mouse peritoneal macrophages in a dose-dependent manner. However, K112PC-5 did not affect concanavalin A-induced proliferation, interleukin (IL)-2 secretion and IL-4 secretion in mouse splenocytes. In addition, K112PC-5 significantly suppressed the increase in phorbol ester-induced ear thickness in BALB/c mice. Further study demonstrated that topical application of K112PC-5 also inhibited AD induced by extracts of dust mites, Dermatophagoides pteronyssinus and Dermatophagoides farinae, in NC/Nga mice. Taken together, these results showed that K112PC-5 exerted an anti-inflammatory effect both in vitro and in vivo and proved to be beneficial in an animal model of AD. Our results suggest that K112PC-5 might be beneficial as a topical agent for the treatment of AD.