Abstract
Chronic pruritus is a major and distressing symptom of many cutaneous diseases, however, the treatment remains a challenge in the clinic. The traditional Chinese-Japanese medicine (Kampo medicine) is a conservative and increasingly popular approach to treat chronic pruritus for both patients and medical providers. Yokukansankachimpihange (YKH), a Kampo formula has been demonstrated to be effective in the treatment of itching of atopic dermatitis in Japan although its pharmacological mechanism is unknown clearly. In an attempt to clarify its pharmacological actions, in this study, we focused on the inhibitory activity of YKH against neurite growth induced with nerve growth factor (NGF) in cultured rat dorsal root ganglion (DRG) neurons because epidermal hyperinnervation is deeply related to itch sensitization. YKH showed approximately 200-fold inhibitory activity against NGF-induced neurite growth than that of neurotropin (positive control), a drug used clinically for treatment of chronic pruritus. Moreover, it also found that Uncaria hook, Bupleurum root and their chemical constituents rhynchophylline, hirsutine, and saikosaponin a, d showed inhibitory activities against NGF-induced neurite growth, suggesting they should mainly contribute to the inhibitory activity of YKH. Further study on the effects of YKH against epidermal nerve density in “itch-scratch” animal models is under investigation.
Highlights
Chronic pruritus is a major and distressing symptom of many cutaneous diseases such as in atopic dermatitis (AD), psoriasis, eczema, urticarial, and xerosis, which has a significant impact on quality of life for patients
YKH consists of nine kinds of crude drugs, and we found that extracts of Uncaria hook ≥ Bupleurum root > Pinellia tuber showed inhibitory activities nerve growth factor (NGF)-induced neurite growth of cultured dorsal root ganglion (DRG) neurons without cytotoxicity at a concentration 100 μg/mL in a following screening assay in order to clarify which one is contribute to the inhibitory activity of YKH
The mechanisms which lead to pruritus and are not fully understood, recent advances have suggested that various peripheral and central mediators should play a role in the pathophysiology of pruritus
Summary
Chronic pruritus is a major and distressing symptom of many cutaneous diseases such as in atopic dermatitis (AD), psoriasis, eczema, urticarial, and xerosis, which has a significant impact on quality of life for patients. A Kampo formula, yokukansankachimpihange (YKH) has been demonstrated to be effective in the treatment of itching of AD [7,8] or chronic urticaria and xerotic eczema patients [9] with psychoneurotic symptoms such as insomnia in Japan, few know about its pharmacological mechanism. Significant cross-talk occurs among stratum corneum, keratinocytes, immune cells, and nerve fibers [12] The latter, in recent studies indicate that the density of epidermal sensory fibers is increased in AD and psoriasis, reduction in the fibers in animal models of AD and dry skin reduces scratching behavior, and suggesting that epidermal hyperinnervation is partly responsible for itch sensitization in cutaneous diseases. This study was focused on the inhibitory activity of YKH against NGF-induced neurite growth in cultured rat DRG neurons in an attempt to clarify its pharmacological actions, and to provide evidence that neurite growth inhibition contributes to better understanding YKH in anti-itching actions in comparison with a positive control neurotropin (NTP), a drug used clinically for treatment of chronic neuropathic pain and pruritus
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