Pruritus is a dominant symptom of many dermatologic disorders (e.g., atopic dermatitis, contact dermatitis and urticaria), and is a frequent manifestation of several systemic diseases (e.g., chronic renal failure and cholestasis). Antihistaminic and anti-allergic drugs are generally prescribed for cutaneous pruritus. However, histamine is not considered to be the major pruritogen in atopic dermatitis, [1][2][3] because histamine H 1 receptor antagonists do not generally depress itch and scratch in patients. Thus, the mechanism of itch in atopic dermatitis is still unclear, and effective treatment is not established.Kampo formulas (traditional Chinese and Japanese herbal medicinal mixtures) are widely used in the clinical treatment of allergic and inflammatory dermatitis in Japan. In some cases, dermatitis improves after Kampo treatment, but the pharmacological characteristics and mechanisms of their action are obscure. Recently, 33 herbal medicines were screened for inhibitory effects on substance P (SP)-induced scratching in mice. 4) However, herbal medicines have not been screened for inhibitory effects on chronic itch-related responses.Previously, we established 5-HT-induced scratching in mice as an acute itch model. 5) 5-HT is pruritogenic in humans, and is suggested to be involved in some pruritic diseases. [6][7][8] We have shown that 5-HT elicits scratching of the treated skin by the hind paws in mice, and that the 5-HT-induced scratching has features similar to those of human itching. 5) The mechanisms of 5-HT-induced scratching may be different from those of SP-or histamine-induced scratching. 9) NC mice are claimed to be a model of atopic dermatitis. 10) When maintained for a long time in a conventional environment, the NC mouse spontaneously and frequently scratches its face, ears and rostral part of the back by the hind paws. 11) We have shown that the spontaneous scratching is thought to be a model of itch-related response in atopic dermatitis. 12) The purpose of the present study is to find new antipruritic herbal medicines that are also effective in treating chronic itch. We screened seven herbal medicines which have been used to treat dermatologic diseases, testing them on mouse models of itch.
MATERIALS AND METHODS
Plant MaterialsThe root of Angelica acutiloba and the root of Saposhnikovia divaricata were provided by the Toyama Medicinal Plant Research Center (Kamiichi, Japan). The fruits of Cnidium monnieri, the root of Cnidium officinale, the fruits of Forsythia suspense, the aerial part of Schizonepeta tenuifolia and the root of Sophora flavescens were purchased from Enjyudo (Toyama, Japan). Fifty grams of crude drugs were extracted three times with methanol (300 ml once, 200 ml twice) for 3 h. The decoctions were evaporated under reduced pressure and dried.Animals Male ICR mice (Japan SLC, Ltd., Shizuoka, Japan) at 4 to 6 weeks of age were used. NC/Jic mice (male, 4-7 months old) were kept for a long time under conventional conditions to induce chronic itch-related responses, as described. 1...