Mechanism of Zizao Yangrong Formula in treating skin xerosis caused by anti-cancer targeted drugs
Objective To explore the molecular mechanism of Zizao Yangrong Decoction (ZYD) in treating skin xerosis caused by anti-cancer targeted drugs based on network pharmacological analysis and animal experiments. Methods Online databases were used to search for the corresponding targets of each single herb included in ZYD and skin xerosis and pruritus. The shared targets were analyzed and used to predict the possible effect pathways through pathway enrichment. Rat model consistent with patients' dry skin lesions by targeting drug gefitinib was established,and were divided into model group,positive control group and Chinese herb group,which were treated by normal saline,vitamin E cream,ZYD respectively. Compared with normal rat,the skin phenotype,histopathological changes,the expression of signal pathway-related proteins and inflammation factors were observed. Results Single herb of ZYD was screened out a total of 3125 predicted targets. Targeted drugs-induced skin xerosis which was accompanied by pruritus and caused by targeted drugs was screened out a total of 660 targets. 173 targets shared by ZYD and diseases were analyzed. Pathway enrichment showed that PI3K-Akt pathway might be the signal pathway of the effect of ZYD. Animal experiments showed that compared with normal group,rats in other groups developed target drug-related skin xerosis like lesion,scrab and desquamation. Compared with model group,the dryness of skin condition of rats in positive control group and experimental group were improved. The improvement of skin healing and hair growth in experimental group were better than that in positive control group. In the model group,Akt protein and p-Akt 308 protein were stained brown and the intensity was weak. Compared with the model group,Akt protein and p-Akt 308 protein in the Chinese herb group were brown,and the intensity was stronger than that in the positive control group,which was similar to that in the normal control group. There was no significant difference in the staining intensity of p-Akt 473 protein among the groups. Western blotting results:compared with the normal control group,the relative expression of p-Akt 308 protein in the skin tissue of Chinese medicine group was lower (P<0.05);compared with the model group,the relative expression of p-Akt 308 protein in the skin tissue of Chinese herb group was higher (P<0.05). There was no significant difference in the levels of inflammatory factors in skin tissue and serum among the groups (P>0.05). Conclusion Chinese herb ZYD might have a therapeutic effect on targeted drugs-associated skin xerosis by relieving inflammatory reaction and promoting skin recovery,in which Akt-related pathway might be involved.
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