Cepharanthine: A Therapeutic Potential Candidate for Psoriasis

Dear Editor:

Psoriasis vulgaris is a recurrent inflammatory cutaneous disease that involves approximately 3% of the population worldwide. ¹ It is typically characterized by erythematous scaly plaques over elbows, knees, scalp, and buttocks. ²

The histology of psoriatic skin is characterized by abnormal epidermal hyperproliferation, dermal angiogenesis, and marked infiltration of inflammatory cells. ³

Psoriasis lesions contain prominent neutrophil aggregation, ⁴ and emergence of neutrophils in the stratum corneum is a defining feature of this disorder. ⁵

Notably, genetic, immunohistochemical, and pharmacologic studies support a prominent role for nuclear factor kappa B (NFκB) pathway in psoriasis pathogenesis. ⁶

Interleukin (IL)-8 is a chemotactic cytokine for all known types of migratory immune cells. High production of IL-8 and/or its receptors has been proven in patients with psoriasis. ⁷

Interestingly, vascular endothelial growth factor (VEGF) mediates neovascularization consequent to binding to VEGF receptors, and it is upregulated in psoriatics. ⁸

It has been documented that the level of nitric oxide (NO) is increased in psoriasis, and researchers have suggested a role for NO in immunopathogenesis of psoriasis. ⁹

Importantly, tumor necrosis factor (TNF)-α has been clarified to be a pivotal pro-inflammatory cytokine in psoriasis disorder. ¹⁰ On the other hand, anti-TNF blockers are able to change the physiopathologic pathway of this disease. ¹¹

It merits note that IL-1β ¹² and IL-6 are thought to play a critical role in psoriasis. Genetic polymorphisms related to IL-6 genes have demonstrated a special pattern of association with psoriasis that could have a potential effect on disease counseling and handling. ¹³

Tekin et al. evaluated the oxidized low-density lipoprotein aggregation in psoriatic cutaneous lesions. They demonstrated that lipid peroxidation mediated by free radicals is one of the important causes of cell membrane destruction and cell damage in psoriasis. ¹⁴

Cepharanthine (CEP) is a biscoclaurine alkaloid extracted from the plant Stephania cepharantha Hayata. ^15,16 It has been extensively used in Japan for the treatment of a wide variety of inflammatory diseases and alopecia aerata and also is considered to have no serious side-effects. ¹⁷

An in vitro study conducted by Murakami and colleagues showed that cepharanthine suppresses the functions of activated neutrophils such as neutrophil elastase release, oxygen radical generation, and neutrophil aggregation. ¹⁸

Importantly, studies have revealed that CEP could inhibit the expression of NFκB, IL-8, VEGF, as well as NO. ^19,20 It is noteworthy that CEP has been recognized to have a protective effect against some of the responses mediated by pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6, and lipid peroxidation. ^16,19

To conclude, because of the potential capability of CEP to suppress neutrophil activation and expression of NFκB, IL-8, VEGF, and NO and also interaction with cytokines such as TNF-α, IL-1β, IL-6, as well as lipid peroxidation, topical CEP might have potential therapeutic advantages as a novel candidate in the treatment of skin psoriasis.

This explanation should serve to motivate colleagues to conduct clinical investigations on this subject. Finally, given the safety of cepharanthine, the authors recommend its topical utility as monotherapy or in combination with corticosteroid therapy in psoriasis.