| Psoriasis is a normal chronic autoimmune skin disease.The clinical features present recurrent erythema and scales,usually throughout the whole body.The skin lesions are often accompanied by itch and ugly scar,which severely impairs the life quality of patients.However,the pathogenesis of this disease is not clear so far.It is seemed that as a chronic disease,immunocytes play an important role for a long time.It is widely accepted that psoriasis is closely related to the combined action of functionally dysregulated keratinocytes,innate immunocytes,activated T cells and some cytokines.Currently,the main therapeutics for psoriasis are immunosuppressive agents,UVB phototherapy or topical agents(steroids).New biological therapies are now under development but still fail to take place of traditional systemic agents,because of poor tolerance with the high expenses and frequent recurrences.This situation forces us to look for more efficient,safer,and more economic drugs for psoriasis.Artemisinin is a natural products derived from Artemisia annua L.,a kind of Chinese traditional herb.Artemisinin and its derivatives have high efficacy and low toxicity in treating malarial agents.More and more scientists are attracted to pay attention to its anti-inflammatory,anti-tumor,immunosuppressive effects with high security.But,it also has disadvantages of low oral bioavailability,which curbed its usage.So we started the studies on how to improve the water solubility and the bioavailability of artemisinin compounds by changing its formulation and structure,then we got a series of artemisinin derivatives.Among them,SM934 is well water-soluble with relatively low cytotoxicity,so we chose it as a drug candidate to treat psoriasis.In our study,we aim to explore the effects of SM934 on psoriasis in vivo and in vitro.In vivo,gel formulation of SM934 was prepared in advance,40 BALB/c mice were divided randomly into 5 groups,named: blank control group,gel matrix group,1% SM934 group,2% SM934 group,tretinoin group.Drug was used on the mouse tail twice a day,for 14 days totally.Then take about 2 cm dorsal skin from tail end.After HE staining,we observed the effects of SM934 on the formation of granular layer in mouse tail scale epidermis in a microscope,and counted the orthokeratosis.In a result,SM934 has a significant promoting effects on the formation of granular layer in mouse tail scale epidermis,and it also obviously promotes the keratinization of keratinocytes.The water soluble artemisinin derivative SM934 was proved of low toxicity on HaCaT cell by the CCK8 cell toxicity experiment.Clinically,patients with psoriasis had high level of IL-6,IL-8,K17,S100A8 in skin lesions and there was a positive correlation between the increase level of cytokines and the skin lesion severity.ELISA and RT-PCR experiments showed that HaCaT cells secreted high level of cytokine IL-6 stimulated by TNF-α and IFN-γ,also overexpressed CXCL5,IL-6,IL-8,K17,S100A8 under the inducement of TNF-α and IL-17.Meanwhile,SM934 significantly inhibited the expression of those cytokines,restraining the inflammatory responses related to HaCaT cells.In a conclusion: Experiments in vivo showed that SM934 could promote orthokeratosis,and facilitate the formation of granular layer cells.Experiments in vitro showed that SM934 could inhibit inflammatory response concerned with keratinocytes.So SM934 has certain potential therapeutic effects in the treatment of psoriasis.this research helps the further study of artemisinin derivatives to treat psoriasis. |
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