Clinical Efficacy And Mechanism Of Traditional Chinese Medicine Foot Bath In The Treatment Of Chemotherapy-induced Peripheral Neuropathy By Taxane

Background: Taxane plays an anti-tumor effect by stabilizing microtubules,inhibiting the mitosis and trigger apoptosis of cancer cells,which effectively preventing the proliferation of cancer cells.It has been used in the treatment of breast cancer（BC）,ovarian cancer,lung cancer and other malignant tumors widely.Although,Taxane drugs are effective,the peripheral neurotoxicity caused by this drug affects the quality of life of patients seriously.Therefore,in this study,BC patients with chemotherapy induced peripheral neuropathy（CIPN）by taxane drug treatment in the Oncology Department of The First Hospital of Lanzhou University were given the self-designed Chinese medicine foot bath numbing formula in order to analyze which clinical effect.In addition,we explore the mechanism of improving CIPN by foot bath numbing formula through network pharmacology.Part 1 The Clinical Efficiency of Foot Bath Numbing Formula on the Treatment of CIPN by TaxaneObjective: To explore the clinical efficiency of Foot Bath Numbing Formula on the treatment of CIPN by Taxane.Methods: This study included BC patients who developed CIPN by taxane treatment from July 2021 to January 2022 in The First Hospital of Lanzhou University.They were randomly assigned to the mecobalamin group（treated by mecobalamin）,the combination group（treated by mecobalamin combine foot bath numbness prescription）,and the traditional Chinese medicine group（treated by foot bath numbness prescription）by digital method.The changes of CIPN grades before and after treatment（28 days）were observed.Meanwhile,the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale（EORTC QOL-C20）were evaluated to explore the quality of life of patients.Results: A total of 90 patients were included in this study,of which 2 patients in the mecobalamin group were excluded because they were not treated according to the experimental protocol,and 88 patients finally completed the experiment.The results showed that the CIPN grades in the three groups before treatment were mainly grade 2.After treatment,the CIPN grades in the combination group and the traditional Chinese medicine group were mainly grade 1,and the mecobalamin group was mainly grade 2,and the difference was statistically significant（p<0.05）.The effective rates in the combination group and the traditional Chinese medicine group were 76.7% and 73.3%respectively,which were significantly better than those in the mecobalamin group（46.4%）.However,there was no significant difference in the efficacy between the combined group and the traditional Chinese medicine group（p=0.944）.In addition,the quality of life of patients in the three groups was improved compared with the previous one（p<0.05）.Further analysis found that the quality of life of the combined group and the traditional Chinese medicine group was more significantly improved than that of the mecobalamin group（p<0.05）.In terms of security,only 2 patients had a small amount of rash（3.3%）,which could be relieved spontaneously after drug withdrawal,no obvious liver and kidney function damage was found in all patients.Conclusion: The foot bath numbing prescription can relieve the CIPN by Taxane effectively and improve the quality of life of patients significantly,which can be used as an optional solution for the treatment of CIPN.Part 2 Exploring the Mechanism of Foot Bath Numbing Formula in the Treatment of CIPNObjective: Using network pharmacology to explore the mechanism of foot bath numbing formula in the treatment of CIPN.Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP）was used to retrieve the main chemical components of all Chinese herbal medicines in the Chinese medicine Foot Bath Numb Prescription and to collect the corresponding targets.Gene Cards database,On-line Mendelian Inheritance in Man（OMIM）,and Pharmacogenomics Knowledgebase（Pharm Gkb）were used to collect CIPN disease targets.The intersection genes and the networks of "component-target" were built by R and Cytoscape software.The protein-protein interaction（PPI）network was built by String,and enrichment analysis for the core target and signaling pathways were analysed by R software finally.The corresponding targets of each herbal medicine in the Chinese herbal numbness formula were analyzed,and the signaling pathway and mechanism of action in the treatment of CIPN were explored.Results: Using the above method,125 active ingredients,214 drug targets,853 disease targets,and 88 intersection genes were finally obtained.PPI network analysis showed that the core proteins were AKT1,CASP3,VEGFA,IL6,and JUN."Ingredienttarget" network analysis showed that the core components were quercetin,luteolin,kaempferol,and β-carotene.GO enrichment analysis revealed 2205 functional items,including 28 cellular components,2042 biological processes,and 135 molecular functions,which mainly including nuclear receptor activity,ligand-activated transcription factor activity,ubiquitin-like protein ligase binding,cytokine activity,and nuclear hormone receptor binding etc.The KEGG pathway enrichment analysis has enriched a total of 176 It mainly involves signaling pathways such as PI3K-Akt,NFkappa B,MAPK and HIF-1.Conclusion: Through the analysis of network pharmacology,we found that the traditional Chinese medicine foot bath numbing formula acts on AKT1,CASP3,VEGFA,IL6,JUN and other targets through active ingredients such as quercetin,luteolin,kaempferol,and β-carotene.PI3K-Akt,NF-kappa B,MAPK and HIF-1 and other signaling pathways were regulated to achieve the effect of treating CIPN.