1,4-dihydroxy-2-naphthoic Acid Induces Apoptosis in Human Keratinocyte: Potential Application for Psoriasis Treatment

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.

Retracted: MicroRNA‐181b negatively regulates the proliferation of human epidermal keratinocytes in psoriasis through targeting TLR4

“…The subgroup for this disease mainly includes psoriasis vulgaris (also called plaque psoriasis), pustular psoriasis, psoriatic arthritis and erythrodermic psoriasis clinically [3,4], characterized by excessive growth of the epidermal layer of the skin, chronic inflammation in the dermis and parakeratosis [5]. Currently, the aetiology of psoriasis is not fully understood, but genetics, cell apoptosis and proliferation, immunity, inflammation and neurotransmitters are reported to be involved [6][7][8]. Although typical medications of psoriasis involve retinoid acids [9], methotrexate [10], cyclosporine [11], compound glycyrrhizin [12], few of them have targeting effects because of the complexity of psoriasis.…”

Antiproliferation of keratinocytes and alleviation of psoriasis by the ethanol extract of Artemisia capillaris

“…Psoriatic keratinocytes are prone to resist against apoptosis, and it may be one of principal pathogenic mechanisms of psoriasis (Kaštelan et al, ). It was reported that the alleviation of psoriasis can be predicted from the apoptotic effects in HaCaT cells (Mok, Xie, Sham, Lin, & Cheng, ; Sun, Han, Zhao, Zhu, & Hu, ). The apoptotic effect of ACE was identified by the externalization of phosphatidylserine in HaCaT cells as shown in Figure b.…”

“…Cell cycle arrest assay was performed in HaCaT cells after incubating with ACE (Figure f). The antipsoriatic properties of natural products have been assessed by the cell cycle arrest assay in HaCaT cells (Mok et al, ; Tse, Cheng, Che, Zhao, & Lin, ). The apoptotic potential of ACE in HaCaT cells was evaluated by the alteration of subG0/G1 population percentage in cell cycle arrest assay (Mok et al, ).…”

“…The antipsoriatic properties of natural products have been assessed by the cell cycle arrest assay in HaCaT cells (Mok et al, ; Tse, Cheng, Che, Zhao, & Lin, ). The apoptotic potential of ACE in HaCaT cells was evaluated by the alteration of subG0/G1 population percentage in cell cycle arrest assay (Mok et al, ). The population percentage of subG0/G1 phase in ACE group was 2.2‐fold higher than that of control group ( p < .05).…”

FOS-like antigen 1 is highly expressed in human psoriasis tissues and promotes the growth of HaCaT cells in vitro

“…Apoptosis is the selective process of physiological cell deletion that regulates the balance between cell proliferation and cell death. The failure of apoptosis is considered to contribute to the development of certain human diseases, such as psoriasis, non-alcoholic fatty liver disease and acute myelogenous leukemia (22,23).…”