The Effects of Indigo naturalis on the Desmosemal Proteins in Psoriasis

The efficacy of indigo naturalis in treating psoriasis has been validated in our clinical studies. Indigo naturalis has also been demonstrated to regulate hyperproliferation and abnormal differentiation in epithelial keratinocytes, as well as aid in the recovery of impaired epidermal barrier function. The impairment of epidermal barrier function may occur subsequent to disorders of the adherens junctions and desmosomes. Desmosomes provide strength and rigidity to cells and contribute to tissue morphogenesis and certain cellular processes. Our preliminary studies using cDNAmicroarray technique to identify the gene expression in epidermal keratinocytes treated by indigo naturalis showed numerous genes were promoted, such as involucrin, desmoglein, tight junction protein and plakophilin, etc. In addition, we also found that the expression of desmoglein 1(DSG1), junctional plakoglobin (JUP), and plakophilin 1 (PKP1) in psoriatic skin lesions are lower than normal. This three-year study aims to construct in vitro models using epidermal keratinocytes and further investigate the pharmacology of indigo naturalis in desomosal proteins. We will also identify the active components of indigo naturalis and investigate the pharmacological mechanism of the active components. In the first year, we will compare the expression of desmosomal proteins, such as DSP、DSG1、JUP、PKP in psoriatic lesions before and after indigo naturalis treatment using immunofluorescence analysis. The gene expression of desmosome related proteins in epidermal keratinocytes treated with indigo naturalis will also be assayed by in vitro models. In the second year, we will identify the active components’ effect on the expression of desmosomal proteins and investigate their pharmacology, as well as investigate the synergistic effects of different components. In the third year, we will identify the signaling pathway of desmosomal protein expression in indigo naturalis-treated cells using specific kinase inhibitors and investigate the related mechanisms using siRNA technology. We expect indigo naturalis may have multiple active components which regulate the expression of desmosomal proteins in epidermal keratinocytes. Each active component may regulate gene expression of desmosomal proteins through different signaling pathways. The results of this study should improve our understanding of the pharmacologic mechanism and active components of indigo naturalis in psoriatic treatment and suggest applications in the treatment of other dermatosis in the future.

Project ID:PC10007-1162
External Project ID:NSC100-2320-B182-024