Study On The Mechanism Of Thymol In The Treatment Of Atopic Dermatitis And Psoriasis

Itch is caused by skin diseases such as atopic dermatitis,eczema,psoriasis,urticaria and xerosis.Itch is the unpleasant feeling that causes the desire to scratch,and the scratch caused by chronic itching can aggravate the skin damage.Itch and scratch can cause sleep loss and seriously affect the quality of life of patients.The treatment of chronic itch is still a clinical challenge.Because itch involves complex interactions between skin issue and immune cells,the exact mechanisms and target drugs for ACD and psoriasis are still unknown.At present,the clinical treatment for ACD includes local glucocorticoids,emollients,immunosuppressants,etc.The main treatment for psoriasis is to suppress the inflammatory response through biotherapy,including TNF-inhibitor,phototherapy form,calcineurin inhibitor,retinoic acid drug and immunosuppressant,etc.However,these methods are all accompanied by adverse reactions and drug dependence,and some of the treatment methods are expensive,making the treatment of ACD and psoriasis difficult.Thymus mongolicus Ronn is a perennial aromatic plant of the genus thyme in the labiaceae family,which is also known as thyme,ground pepper,and pepper.It tastes pungent,warm,little poison.Thymol contains many active ingredients,such as thyme phenol,catechol,flavonoids and glycosides and other polyphenols antioxidants,which has the effect of removing rheumatism and expelling cold.Thymol,also known as thymol,is a monoterpene phenol that is one of the most important dietary components of the thyme family.For centuries,it has been widely used in traditional medicine,and has set up a show with a variety of pharmacological properties,including antioxidants and radical scavenging,anti-inflammatory,analgesic,antispasmodic,antibacterial,antifungal,anti-corrosion and antitumor activity.However,there is no report of thyme phenol for atopic dermatitis and psoriasis treatments and corresponding mechanisms.To explore the therapeutic activity and potential pharmacological mechanism of thymol in treating these diseases,a model of atopic dermatitis induced by SADBE and a model of psoriasis induced by IMQ were established.In the SADBE model,thymol significantly reduced the number of spontaneous scratching in mice,reduced the levels of TNF-α、IL-1β、IL-4、IL-6 and IFN-γin serum and skin tissues,significantly alleviated the symptoms of skin barrier damage and the infiltration of mast cells into the dermis.In an in vitro model of macrophage inflammation induced by lipopolysaccharide（LPS）,thymol significantly inhibited the expression of p-P38 and p-Erk in the MAPK signaling pathway,and decreased the m RNA levels of inflammatory cytokines TNF-α、IL-1βand IL-6 in the downstream of the MAPK pathway.Therefore,it is concluded that thymol may regulate the expression of Th1/Th2 cytokines by blocking the MAPK signaling pathway in macrophages to exert its efficacy.Thymol has good anti-inflammatory and antipruritic effects and maybe a potential effective drug for the treatment of atopic dermatitis.In the IMQ model,thymol significantly reduced the number of spontaneous scratching in mice and had stronger anti-psoriasis effect than dexamethasone.Calcium imaging of neck DRG neurons showed that thymol activates trpm8-mediated Ca²⁺response.Besides,scratching results from Trpm8^-/-mice or pretreated with Trpm8 inhibitor RQ confirmed that thymol alleviates itch by stimulating Trpm8 in DRG neurons.Thymol can significantly relieve the symptoms of damaged skin barrier,epidermal thickness hyperplasia and infiltration of mast cells into the dermis in mice.Flow cytometry and immunofluorescence showed that thymol reduced the infiltration of dendritic cells（DCs）,neutrophils,and Th17 cells in psoriatic lesions.In addition,thymol significantly down-regulated the expression levels of the pro-inflammatory cytokines TNF-α,IL-17,IL-22,IL-23,IL-6,IL-1βand IFN-γin skin tissues and serum in the IMQ model.In short,thymol is effective in relieving itch induced by IMQ by activating the trpm8-mediated Ca²⁺response,and its anti-inflammatory effect is related with downregulating the infiltration of DCs,neutrophils,and Th17 cells in IMQ lesions and reducing the expression of various pro-inflammatory cytokines.In summary,thymol has a good therapeutic effect on atopic dermatitis and psoriasis by inhibiting the activation of itch and inflammation-related signaling pathways,reducing the activity of inflammatory immune cells and the expression of downstream inflammatory factors.Furthermore,thymol has the potential to be a clinically effective treatment for chronic itch due to its healthy and harmless natural source and its properties as a dietary supplement or pharmacological adjuvant.