Applications of Traditional Chinese Medicine on Psoriasis Treatment.

摘要

Psoriasis is a chronic inflammatory skin disorder that affects approximately 1-3% of the population worldwide. It is characterized by epidermal hyperplasia or abnormal differentiation, infiltration of leucocytes into the dermis and epidermis, dilation of blood vessels in dermis and inflammation. Evidence indicates keratinocytes contributed to the disease, and keratinocytes also participate in maintaining the chronically perpetuating immune response that sustains psoriasis. Decrease in keratinocytes apoptosis is suggested to be a specific pathogenic phenomenon, and induction of keratinocytes apoptosis have long been considered as an effective anti-psoriatic strategy.;Treatment of psoriasis is based on disease severity. Topical agents are predominantly for mild conditions; phototherapy for moderate conditions and systemic treatment or biological agents for severe cases. Topical treatment remains the most widely used method as an estimated 75% of psoriatic patients have mild to moderate disease. Chinese herbs have been used for the treatment of psoriasis in China, and studies showed their mechanism on treating psoriasis may through inhibition of keratinocyte proliferation and induction of apoptosis. Comparison studies also show that traditional Chinese medicine has relatively fewer side effects than western therapeutic agents, with a longer remission time and lower recurrence rate.;The extract of the root of Rubia cordifolia L. (Rubiae Radix et Rhizoma) was previously found to inhibit keratinocyte proliferation using a psoriasis-relevant HaCaT cells model. In this study, the ethyl acetate extract of the root of Rubia cordifolia L. (EA) was confirmed to induce apoptosis on HaCaT cell, and the antiproliferative effect of EA is more potent than the ethanol extract of the herb (EE) and is comparable to dithranol, an important and popular topical treatment for psoriasis among Europe countries. Besides, we identified one of the components in Rubia cordifolia L., 1,4-dihydroxy-2-naphthoic acid (DHNA), could induce HaCaT keratinocyte apoptosis through the death receptor and mitochondria mediated pathway as well as in a caspase independent manner using various assays such as morphological examination, annexin V-PI staining, cell cycle analysis, DNA fragmentation, TUNEL assay, immunofluorescence staining and Western blot analysis. Moreover, DHNA was found to induce keratinocyte differentiation in a preliminary study using the in vivo mouse tail model of psoriasis. Furthermore, results from in vitro (cell viability, IL-1α release) and in vivo (Draize animal skin irritation test) experiments suggested DHNA have less irritation problems than dithranol.;In summary, this study describes the apoptotic mechanism of EA and DHNA, as well as the irritation potential of DHNA using different human skin cells and animal model. These results suggest EA and DHNA have the potential to develop as safe and effective therapeutic alternative for the treatment of psoriasis. EA and DHNA can be used together in a sequential therapy, in which EA is effective in rapid clearing of psoriatic lesions as its potency is comparable to dithranol; whereas DHNA is better suited for the later maintenance therapy for its milder irritation effect compared with dithranol.