Cellular And Molecular Mechanisms Of Qingpeng Ointment In Treating Acute And Chronic Dermatitis Pharmacology

Qingpeng ointment as a topical Tibetan medicine preparation,including Oxytropis,Yadahuang,Aconitum pendulum Busch,Myrobalan(stoned),emblic,benzoin,Kuanjinteng and artificial musk etc.In Tibetan medicine,Qingpeng ointment is beneficial for blood circulation,anti-inflammatory and acesodyne.It has curative effect on gout,rheumatism,rheumatoid arthritis and the joint swelling and pain,sore bruise,skin itching,eczema which caused by thermal "Gangba" and "Grasserie" disease and so on.Among them,the original intention of Grasserie disease not only refers to the general skin eczema,scabies and other lesions exudate.It actually slightly equivalent to the wet and dampness of Chinese medicine.Grasserie causes urticaria on the skin;in the joints can cause arthritis;in the viscera can cause visceral Grasserie ponding,visceral abscess and so on.Grasserie is found throughout the body and more on the skin and joints.Its nature is neither hot nor cold but cold and heat after the disease.The skin itching belongs to the "yellow water disease" category of Tibetan medicine,in Tibetan medicine that itchy skin is due to the occurrence of diet few,much,on the contrary and other abnormal changes due to the disorder,causing Grasserie become strong or weak and due to itchy skin pruritus.Tibetan medicine treatment of pruritus is based on the treatment of Grasserie disease.Allergic contact dermatitis(ACD)is a chronic,relapsing,inflammatory dermatosis.Dysfunction in Th cells and IgE is considered to be the most important factor in the pathogenesis of ACD.In this study,based on a large amount of literatures,we found that Qingpeng ointment has a clinically significant effect on the pruritus diseases and try to construct ACD model to explore the function of Qingpeng ointment to improve the pruritus degree of the disease.However,Qingpeng ointment in the treatment of allergic contact dermatitis mechanism of action has rarely been reported.Based on the network pharmacology,this study systematically studied the mechanism of Qingpeng ointment in the treatment of acute itch and allergic contact dermatitis caused by histamine at the carrier,molecular and genetic level supported by animal experiments.In this paper,we collected the compounds known by Qingpeng ointment in the medicinal materials of nine herbs for network pharmacological analysis,and based on the multidimensional information of disease-phenotype-gene-drug and based on network pharmacology,we can understand the disease or symptom from the chart,system and network type and biological molecules,the use of this "disease/syndrome phenotype-molecular network of ideas." Based on the platform of BATMAN-TCM,target prediction methods were used to predict the potential targets of TCM-based compounds based on similarity.The essence is to calculate the similarities by comparing their interactions with known drug targets and to rank potential drug target interactions.From the experimental results,we know that Qingpeng ointment may play a role through the NF-κB and MAPK pathways and achieve the purpose of improving skin diseases through the cytokines such as IL-4,IL-5 and TNF,We are validated from pharmacodynamic experiments.We build histamine-induced animal model of acute itching and SADBE-induced allergic contact dermatitis(ACD)model,through behavioral scratching observed Qingpeng ointment can play both the treatment of both itching.Qingpeng ointment can significantly inhibit the levels of IgE,histamine,TNF-α,IL-1β and IL-4 in mice induced by histamine in acute itch behavior test,and at the gene level can significantly inhibit the content of IL-4 and TSLP in the skin.Thus obtained Qingpeng ointment through the regulation of Th1 / Th2,with anti-inflammatory,anti-allergic and itching effect.To explore the mechanism of Qingpeng ointment in the treatment of allergic contact dermatitis,we explored the related pathways and cytokines provided by network pharmacology.On the basis of significantly improving the degree of pruritus in mice,it was found that Qingpeng ointment can reduce the level of serum cytokines such as IgE,IL-5 achieve anti-inflammatory effect.And at the gene level,Qingpeng ointment was found to be able to achieve antipruritic effect through transient ion channels such as TPRV1,TPRA1 and TRPV4 associated with itch,further study of itching molecules such as GRP,TSLP and MrgprA3 obtained Qingpeng ointment can significantly reduce these itch molecules In the skin or dorsal root ganglia(DRG)content,verify Qingpeng ointment itching efficacy.Western blotting confirmed that Qingpeng Ointment had a down-regulated effect on the phosphorylation of phosphorylated P38 and phosphorylated Erk in ACD mice,indicating that Qingpeng Ointment can improve the allergic contact dermatitis through the MAPK signaling pathway.In summary,the prescription of Tibetan medicine Qingpeng Ointment is unique in that it has a remarkable curative effect in the treatment of pruritus and is a kind of external medicine with anti-inflammatory,anti-allergic and anti-itch effects,which can not only avoid oral and systemic administration to the liver Kidney and other damage,but also through the antagonism and allergy and inflammation-related signaling pathways,interfering with inflammation-related immunologically active molecular pathway,blocking the sensory pathway associated with signaling molecules,so as to achieve the role of treatment.Through the study of its mechanism of action,it can provide ideas for new drugs for the treatment of pruritus diseases in the same kind and has good clinical application prospect.