Atopic dermatitis (AD) is a common skin disease characterized by pruritus, eczematous skin lesions, and a chronically relapsing course.2) The pathogenesis of AD is multifactorial, and genetically determined immunologic aberrations are thought to play an important role in it. The mechanisms involved in disease development are incompletely understood, but mite antigen is thought to be one of the pathogens because patients have elevated serum levels of immunoglobulin-E (IgE) against the allergen.3) There is some evidence that T-cell responses to the allergen are crucial for AD aggravation. 4) It has been accepted that topical steroid therapy is crucial for AD management, but they cannot be used for long periods because of frequent side effects. Steroid therapy can improve topical cutaneous symptoms, but cannot completely cure the disease. Many patients therefore choose to explore complementary/alternative medicines including herbal medicine.5) Traditional Chinese medicine (TCM) and traditional Japanese medicine (Kampo) have been receiving increasing attention as alternative sources of treatment for chronic diseases, including AD. TCM is believed to have the potential to treat patients holistically by supporting the patient's selfhealing power.6,7) However, the dearth of scientific evidence of TCM has restricted its polular use.A murine strain, NC, is a well-known animal model for AD and has been extensively used to elucidate AD pathogenesis and development. NC mice spontaneously develop ADlike eczematous skin lesions with IgE hyperproduction when raised under conventional conditions, but not under specific pathogen-free conditions.8) It was revealed that environmental antigens such as Dermatophagoides farinae (Df) were involved in the pathogenesis of AD-like symptoms in NC mice. Repeated extraneous injections of the antigen to NC mice caused severe and settled dermatitis, which could then be used as a model to evaluate new pharmaceutics for AD treatment. 9-11)We evaluated the effect of bakumijiogan (BJG) on the AD model induced by repeated Df-antigen injections in NC/Jic mice. BJG is a modified herbal formula of rokumigan. Rokumigan consists of six crude drugs (Table 1) and is a basic formula used to treat kidney-yin deficiency, which according to the TCM theory is a condition characterized by tidal fever, spontaneous sweating, dizziness, tinnitus, spermatorrhea (in males), and sexual intercourse in dream (in famales). Six crude drugs contained in rokumigan and two additional crude drugs, ophiopogon tuber (bakumondo in Japanese, B) and schisandra fruit (gomishi in Japanese, G), constitute BJG (Table 1). In the TCM theory, the targeted conditions for BLG use include deficiency of lung-kidney-yin, reversed flow of qi, tidal fever, and night sweats. BJG has therefore been given to patients with asthma, AD, or systemic lupus erythematosus. 12) MATERIALS AND METHODS Preparation of Herbal FormulasAll crude drugs in the Japanese Pharmacopoeia XV 13) were purchased from Tsumura Co. Ltd. (Tokyo). The composition of BJG and ...

Ethenzamide (ETZ), an antipyretic analgesic categorized as a non-steroidal anti-inflammatory drug (NSAID), is widely used as an over-the-counter (OTC) drug in combination with other NSAIDs. However, its site of action and mechanism underlying its analgesic action have not yet been fully elucidated. In this study, we performed in vitro pharmacological assays to identify the mechanism underlying the analgesic action of ETZ, and also conducted the rat formalin test to investigate its analgesic effect and site of action.Of the 85 receptors, ion channels, transporters and enzymes tested, we found that ETZ binds to the 5-hydroxytryptamine (5HT) 2B receptor in concentration-dependent manner with modest inhibitory effects on monoamine oxidase-A and transient potential vanilloid 1 channel. The 5HT 2B receptor antagonist activity of ETZ was also confirmed in a cellular functional assay. Furthermore, the drug exerted no inhibitory effects on cycrooxygenase-1 and -2. In the rat formalin test, oral administration of ETZ significantly reduced the nociceptive responses of the second phase and also the number of c-Fos-expressing cells in the spinal dorsal horn, in a dose-dependent manner. Moreover, intrathecal administration of ETZ significantly reduced the nociceptive responses. These results suggest that the analgesic effect of ETZ is exerted at least in the spinal cord, and the effect would be attributed to multiple mechanisms of action including 5HT 2B receptor blockade.