Abstract:

Objective To screen the active components of Tongluo Tangtai Power（TLTT） in the treatment of diabetic peripheral neuropathy（DPN），predict the action targets and signaling pathways by network pharmacology，and to explore its mechanism. Methods The Traditional Chinese Medicine System Pharmacological Analysis Platform （TCMSP） was used to collect the main chemical components and action targets of TLTT；Genecard Database was used to retrieve the proteins associated with DPN； the protein-protein interaction（PPI） network was constructed by STRING Database and network visualization software Cytoscape3.9.1； pathway enrichment analysis and composition-target docking were analyzed by the Kyoto Encyclopedia of Genes and Genomes （KEGG） and molecular docking technique. Thirty SD rats were divided into control group， mecobalamin group， and TLTT group， and there were 10 rats in each group.The rats were given mecobalamin and TLTT by gavage to make the drug-containing serum； one stain of RSC96 Schwann cells was resuscitated；control group， high glucose model group， mecobalamin group， and TLTT group were set up；then cell counting method was used to detect the survival rates of Schwann cells in various groups； Western blotting method was used to detect the expression levels of serine/threonine kinase 1（AKT1） and tumor suppressor gene TP53 proteins in the cells in various groups. Results There were 95 active compound components and 463 targets in TLTT for the treatment of DPN， 1 187 DPN-related proteins， and 137 drug-disease common targets.The Geno Ontology（GO） analysis，including biological processes， cell composition，and molecular function） results obtained 5 505， 466， and 791 results；the KEGG analysis obtained 253 results，suggesting that TLTT may played a therapeutic role by regulating the phosphatidyl inositol 3 kinase/protein kinase B （PI3K-Akt） signaling pathway， liquid shear stress and atherosclerosis， advanced glycosylation end products and their receptors （AGE-RAGE），mitosolysis-activated protein kinase （MAPK） singling pathways and so on；the molecular docking results showed that TLTT acted on AKT1，TP53，tumor necrosis factor（TNF），epidermal growth factor receptor（EGFR），and other core targets by some core components such as quercetin，sterol，beta-sitosterol， kaempferol， ivy saponin，and so on. The CCK-8 results showed that compared with control group，the survival rate of the cells in high glucose model group was significantly decreased（P<0.05）；compared with high glucose model group，the viability of the cells in TLTT group was significantly increased （P<0.05）.The Western blotting results showed that compared with control group， the expression level of AKT1 the cells in high glucose model group was significantly decreased（P<0.05）， and the expression level of TP53 protein was significantly increased （P<0.05）；compared with high glucose model group， the expression level of AKT1 protein in the cells in TLTT group was significantly increased（P<0.05）， and the expression level of TP53 protein was significantly decreased（P<0.05）. Conclusion The main active components of TLTT， such as quercetin， may promote the survival of the Schwann cells， increase the expression level of AKT1 protein and decrease the expression level of TP53 protein by targeting PI3K-Akt and other signaling pathways， so as to play a role in the treatment of DPN.

Key words: Tongluo Tangtai Power, Diabetic peripheral neuropathy, Network pharmacology, Molecular docking, Schwann cell