Basic and clinical evaluation of Juzen-taiho-to usedin atopic dermatitis

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15590607
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General internal medicine (including Psychosomatic medicine)
• Research Institution: Meijo University
• Principal Investigator: OGIHARA Yukio Meijo University, Faculty of Pharmacy, Professor, 薬学部, 教授 (70080166)
• Co-Investigator(Kenkyū-buntansha): NOSE Mitsuhiko Nagoya City University, Graduate School of Pharmaceutical Sciences, Assistant professor, 薬学研究科, 講師 (60228327)
• Project Period (FY): 2003 – 2004
• Keywords: atopic dermatitis / Kampo medicine / Juzen-taiho-to / NC mice / 2.4.6-trinitrochlorobenzene / regulatory T cell

Research Abstract

Atopic dermatitis (AD) is an acute, subacute or chronic pruritus dermatitis with other findings, such as xerosis, excoriations and lichenification, often occurring in person with asthma, allergic rhinoconjunctivitis, contact urticaria or with a family of the same. Itching and dryness of the skin are the cardinal symptoms the morphology of the lesions is the same as in other eczemas. More than 80% of the patients with AD have elevated levels of serum IgE with specificity to various environmental allergens to which they also demonstrated immediate-type skin reactions.
The mainstay of therapy for AD remains topical steroids. However, there is no single treatment that is effective to completely cure the symptoms of AD in all patients at the present. Recently the immunosuppressive agents are also available but still not enough. Therefore, a variety of therapies are used for the treatment, including Kampo medicines in Japan. Kampo medicines are clinically and widely used for allergic and infl ammatory diseases but unfortunately their pharmacological properties and mechanisms of immunopharmacological actions are still not fully understood.
In our study, we investigated the effects of these Kampo medicines on the onset and symptoms of AD model, induced by repeated application of 2,4,6-trinitrochlorobenzene in NC/Jic mice. We found that Juzen-taiho-to (JTT) significantly suppressed the symptoms and progress of AD-like dermatitis. Topical application of TNCB on ears once a week for 7 weeks gradually caused chronic edema with atopic dermatitis-like symptoms such as hemorrhage, excoriation, erosion and scaling. Serum total IgE level was also increased and massive invasion of activated mononuclear cells in epidermis and massive infiltration of eosinophils and neutrophils in dermis were histologically observed. Oral administration of JTT significantly suppressed the ear edema and progression of atopic dermatitis-like symptoms. It also reduced the increase of serum total IgE level and the infiltration of mononuclear cells in epidermis and eosinophils in dermis. In cervical lymph nodes, T cell ratio and CD4/CD8 ratio were significantly reduced in the control group but JTT improved their reduction, suggesting that JTT suppressed the traffic of lymphocytes from the draining lymph nodes into inflammatory lesion. RT-PCR analysis revealed that JTT suppressed the increase of mRNA expressions of IL-4 and IFNγ in cervical lymph nodes and TNFα, IL-1β, IL-4, eotaxin and CCR3 in ears, supporting the histological and flow-cytometric analysis. Furthermore, adoptive transfer experiments suggested that regulatory property might be involved in the suppressive actions of JTT in this chronic dermatitis. In conclusion, JTT could be regarded as a useful remedy for atopic dermatitis.

Research Products

• [Journal Article] Sho-saiko-to and Saiko-keishi-to, the traditional Chinese and Japanese herbal medicines, altered hepatic drug-metabolizing enzymes in mice and rats when administered orally for long time (2003)
  • Author(s): Nose, M., Tamura, M., Ryu, N., Mizukami, H., Ogihara, Y.
  • Journal Title: Journal of Pharmacy and Pharmacology 50 Pages: 1419-1426
  • Description: 「研究成果報告書概要(和文)」より