Atopic dermatitis (AD) is a common inflammatory skin disease with recurring episodes of itching and a chronic relapsing course. Current treatment options for AD include topical agents, such as ...topical corticosteroids and oral antiallergic drugs. Providing effective long-term treatment is sometimes difficult due to the chronic, relapsing nature of AD; therefore, there is a need to identify better therapeutic options with minimal side effects that are well tolerated over the variable course of the disease. Traditional herbal medicine, also known as Kampo medicine in Japan, has a long history and plays a role in the prevention and treatment of various diseases, including AD. Some Kampo medicines are useful for treating inflammatory skin diseases, and there has been increased interest in using Kampo medicine to develop new therapeutic agents for AD. Standard Kampo formulas for AD are effective in removing the symptoms of “Netsu Sho,” “Ketsu-Kyo,” “Ki-Kyo,” and “O-Ketsu.” This paper discusses the efficacy of Kampo medicines in treating AD. Knowledge of the mechanisms of action of Kampo medicines will result in greater choices of pharmacotherapeutic agents for AD.
Intra‐cellular reactive nitrogen/oxygen species and apoptosis play important roles in ultraviolet (UV)‐induced inflammatory responses in the skin. Astaxanthin (AST), a xanthophyll carotenoid, ...exhibits diverse clinical benefits. The protective effects of AST against UV‐induced apoptosis were investigated in the present study. Astaxanthin (5 μm) caused a significant decrease in the protein content and the mRNA levels of inducible nitric oxide (iNOS) and cyclooxygenase (COX)‐2, and decreased the release of prostaglandin E2 from HaCaT keratinocytes after UVB (20 mJ/cm2) or UVC (5 mJ/cm2) irradiation. No significant protective effects against UV‐induced reactive oxygen species (ROS) were observed in AST‐pretreated cells. Astaxanthin caused a significant inhibition of UV‐irradiation‐induced apoptosis, as evidence by a DNA fragmentation assay. Furthermore, we found that the treatment with AST caused a reduction in the UVB‐ or UVC‐induced protein and mRNA expression of macrophage migration inhibitory factor (MIF), IL‐1β and TNF‐α in HaCaT keratinocytes. These results suggest that AST effectively protects against UV‐induced inflammation by decreasing iNOS and COX‐2, and thereby inhibiting the apoptosis of keratinocytes.
9,10-Phenanthrenequinone (9,10-PQ), a polycyclic aromatic hydrocarbon that is present in air pollutants, such as diesel exhaust gas and PM2.5, causes the production of excess reactive oxygen species. ...9,10-PQ was recently shown to induce the activation of epidermal growth factor receptor (EGFR) by inhibiting protein tyrosine phosphatase 1B. In the present study, we focused on the non-canonical regulation of EGFR, including negative feedback and internalization. In contrast to previous findings, 9,10-PQ inhibited the constitutive tyrosine phosphorylation of EGFR via the mitogen-activated protein extracellular kinase (MEK)/extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Thr-669 in EGFR-overexpressing A431 and MDA-MB-468 cells. In addition, 9,10-PQ induced the clathrin-mediated endocytosis of EGFR via the p38 phosphorylation of Ser-1015 in HeLa and A549 cells. These results revealed that 9,10-PQ strongly induced the non-canonical regulation of EGFR by activating mitogen-activated protein kinase (MAPK).
Ultraviolet irradiation (UV) exposure is the leading factor underlying the development of skin malignancies. D‐dopachrome tautomerase (D‐DT), a functional homolog of macrophage migration inhibitory ...factor (MIF), has functional similarities to MIF. However, its role, unlike the role of MIF in photocarcinogenesis, is unknown. We therefore explored the role of D‐DT in photocarcinogenesis by developing D‐DT transgenic (D‐DT Tg) mice and provided a research model for future studies targeting D‐DT. Chronic UVB exposure accelerated tumor development in D‐DT Tg mice compared with wild‐type (WT) mice, with a higher incidence of tumors observed in D‐DT Tg mice than in WT mice. In D‐DT Tg irradiated mouse keratinocytes, the p53, PUMA, and Bax expression was lower than that in WT mice. These results indicate that D‐DT Tg overexpression confers prevention against UVB‐induced apoptosis in keratinocytes. Taken together, these findings support D‐DT as a functionally important cytokine in photocarcinogenesis and potential therapeutic target for the prevention of photocarcinogenesis.
Contact dermatitis is produced by external skin exposure to an allergen, but sometimes a systemically administered allergen may reach the skin and remain concentrated there with the aid of the ...circulatory system, leading to the production of systemic contact dermatitis (SCD). Metals such as nickel, cobalt, chromium, and zinc are ubiquitous in our environment. Metal allergy may result in allergic contact dermatitis and also SCD. Systemic reactions, such as hand dermatitis or generalized eczematous reactions, can occur due to dietary nickel or cobalt ingestion. Zinc-containing dental fillings can induce oral lichen planus, palmoplantar pustulosis, and maculopapular rash. A diagnosis of sensitivity to metal is established by epicutaneous patch testing and oral metal challenge with metals such as nickel, cobalt, chromium, and zinc. In vitro tests, such as the lymphocyte stimulating test (LST), have some advantages over patch testing to diagnose allergic contact dermatitis. Additionally, the determination of the production of several cytokines by primary peripheral blood mononuclear cell cultures is a potentially promising in vitro method for the discrimination of metal allergies, including SCD, as compared with the LST.
Ultraviolet (UV) radiation elicits melanogenesis and pigmentation in the skin. Apigenin (4′,5,7‐trihydroxyflavone AGN) is a plant flavone contained in various herbs, fruits, and vegetables. We herein ...investigated antimelanogenic properties of AGN and the molecular mechanisms of the action of AGN. In UVB‐treated mice, AGN inhibited cutaneous hyperpigmentation and macrophage migration inhibitory factor (MIF) expression as a melanogenesis‐related key factor. In mouse keratinocytes, AGN inhibited the expression of MIF and also the related factors (e.g., stem cell factor and proteinase‐activated receptor 2) induced by MIF. In addition to ellagic acid as a casein kinase II (CK2) inhibitor, AGN suppressed CK2 enzymatic activity and UVB‐induced CK2 expression and subsequent phosphorylation of IκB and MIF expression. These results suggest that AGN inhibits UVB‐induced hyperpigmentation through the regulation of CK2‐mediated MIF expression in keratinocytes.
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