Abstract
Psoriasis, which affects approximately 1–3% of the population worldwide, is a chronic inflammatory skin disorder characterized by epidermal keratinocytes hyperproliferation, abnormal differentiation, and inflammatory infiltration. Decrease in keratinocyte apoptosis is a specific pathogenic phenomenon in psoriasis. Chinese herbs have been used for the treatment of psoriasis in China showing promising effect in clinical trials. A traditional Chinese medicine has relatively fewer side effects with longer remission time and lower recurrence rate. The extract of Rubia cordifolia L. (EA) was previously found by us to induce HaCaT keratinocytes apoptosis. In this study we identified one of the components in Rubia cordifolia L., the anthraquinone precursor 1,4-dihydroxy-2-naphthoic acid (DHNA), induces HaCaT keratinocytes apoptosis through G0/G1 cell cycle arrest. We have also demonstrated that DHNA acts through both caspase-dependent and caspase-independent pathways. Besides, cytotoxicity and IL-1α release assays indicate that DHNA causes less irritation problems than dithranol, which is commonly employed to treat psoriasis in many countries. Since DHNA possesses similar apoptotic effects on keratinocytes as dithranol but causes less irritation, DHNA therefore constitutes a promising alternative agent for treating psoriasis. Our studies also provide an insight on the potential of using EA and DHNA, alternatively, as a safe and effective treatment modality for psoriasis.
Highlights
Psoriasis, affecting 1–3% of the population worldwide [1], is a common chronic immune disorder characterized by thickened red plaques with an overlying silver-white scale
Antibodies for Bcl-2, Bcl-xL, p21, p27, Cyclin D1, Cdk2, β-actin were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA); antibodies for caspase-3/7/ 8/9, poly (ADP-ribose) polymerase (PARP), Bid, Fas, Fas-associated death domain (FADD), Cyclin A/D3, Cdk4/6, apoptosis inducing factor (AIF) and endonuclease G (endoG) were from Cell Signaling Technologies (Beverly, MA, USA)
Increased levels of CXCL9/MIG, CXCL10/IP-10, CXCL11/I-TAC [24], and RANTES/CCL5 [26] synthesized by keratinocytes in psoriasis lesions as well as the BRAK/CXCL14 that are upregulated in nonlesional skin of psoriasis patients [24], may activate and initiate the migration of mononuclear leukocytes/T cells/monocytes to the psoriatic lesions
Summary
Psoriasis, affecting 1–3% of the population worldwide [1], is a common chronic immune disorder characterized by thickened red plaques with an overlying silver-white scale. The most common type of psoriasis is psoriasis vulgaris which accounts for 90% of the cases [2]. Affecting both sexes and people of all ages; psoriasis causes significant impacts on the quality of life [3]. Conventional treatments of psoriasis such as topical, phototherapy, and systemic treatment are based on severity of disease. Since an estimated 75% of psoriatic patients have mild-to-moderate disease, topical treatments remain the most widely used [1]. With recent introduction of biological agents, the estimated cost can range from US $13000 to 30000/patient annually [6]
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