The Anti-inflammatory And Antipruritic Effects Of Genistein And Its Molecular Mechanisms

When human body is exposed to various external stimuli,itching is caused by the afferent nerve fibers of the primary sensory nerve.This behavior is usually considered as a mild harmful stimulus.In the physiological sense,itching can also cause people to produce self-protection mechanisms.For example,when people’s skin contacted with irritating substances,it will arouse people’s spontaneous scratching behavior,which will make people quickly avoid the outside world sustained damage in a short time.Allergic contact dermatitis(ACD)is a chronic recurrent inflammatory skin disease.The accompanying itching lasts for a long time and is difficult to heal.In addition,the use of drug intervention to treat the disease will repeat itself which seriously affected people’s quality of life and physical and mental health.The mechanism of pruritus is extremely complex.It is generally believed that when skin tissue is stimulated by harmful external factors,immune cells such as epithelial cells,mast cells,dendritic cells,neutrophils,and macrophages are activated and release a variety of inflammatory mediators,such as TSLP,Histamin,5-HT,CXCL9,TSLP,TNF-α,IL-1β and IL-6,all of which may induce allergic itching.Genistein is one of the main components of soy-based foods,which has been reported potentially to treat obesity,cancer,osteoporosis and cardiovascular diseases.Recently,genistein has been shown therapeutic effects on some chronic skin diseases,but its underlying mechanisms remain unclear.This study explored the antipruritic and antiinflammatory mechanism of genistein,laying a foundation for further clinical research on the development of safer and more effective antipruritic drugs.This topic explores its potential pharmacological effects from in vivo animal experiments and in vitro cell experiments.Firstly,we conducted experiment to study the antipruritic effect of genistein on mice with contact allergic dermatitis induced by SADBE.The successfully immunized male mice were divided into five groups(8 in each group): model group,genistein lowdose group,genistein medium-dose group,genistein high-dose group,and dexamethasone positive control group.At the same time,eight mice treated with acetone alone were used as the normal control group.The results showed that genistein can significantly reduce the scratching number of mice and improve the degree of skin lesions in mice.Next,on the basis of determining the pharmacodynamics of genistein on allergic contact dermatitis,we further explored the molecular mechanism about genistein on ACD.This topic mainly explores the study of genistein on the peripheral mechanism involved in mouse pruritus.We stained the sections of the skin lesions and detected the expression of related inflammatory factors,as well as the phosphorylation of components in MAPK and JAK-STAT3 signaling pathways in the skin and dorsal root ganglions(DRGs).The result indicated that genistein significantly inhibited the increased expressions of pro-inflammatory factors in skin and peripheral blood,and down-regulated the levels of p-ERK,p-p38 and p-STAT3 in the skin and DRGs.In vitro cell experiments found that genistein can directly inhibit the phosphorylation of ERK and STAT3,thereby down-regulating the expression of cytokines and chemokines,and feedback down-regulating phospho-p38 in the Ha Ca T inflammatory cell model induced by TNF-α/IFN-γ.Further study on the effect of genistein on the MAPK pathway,after targeted silencing of the MAP2K2 or MAP2K4 gene in Ha Ca T cells by transfection,the results showed that the inhibitory effect of genistein-mediated MAPK pathway can be si MAP2K2 is reversed,but cannot be reversed by si MAP2K4.Altogether,our findings demonstrated that genistein exhibits good antipruritic and anti-inflammatory effects in ACD mice by inhibiting the production of proinflammatory cytokines and activation of the MAP2K2/ERK cell pathway,which makes genistein a potentially valuable treatment for skin conditions and systemic syndromes in the setting of ACD.This study confirmed the antipruritic effect of genistein on ACD,and dietary genistein supplementation may have a beneficial effect on the progression of ACD and other skin diseases related to chronic itching.