Abstract: AIM: To analyze the mechanism of Jinhutongdan prescription in treating cholelithiasis based on network pharmacology and verify the pharmacological on the active target through animal experiments.  METHODS: (1) The active ingredients of Jinhutongdan recipe were obtained by TCMSP and UniPort. The targets of cholelithiasis treated with Jinhutongdan recipe were obtained by the targets of cholelithiasis related diseases through Genecards database and OMIM database and mapping them with the targets of active ingredients of drugs. Target protein interaction (PPI) network and active ingredients-target network were constructed by Cytoscape3.9.0 software and String database. Using Metascape database to complete GO function and KEGG pathway enrichment analysis, using Cytoscape3.9.0 software to build common target-signal pathway network. We carried out molecular docking by UCSF Chimera1.15 and Autodock-vina software. Top 6 targets ranked by degree value of PPI were selected for molecular docking to verify the binding activity. (2) Forty-eight guinea pigs were randomly divided into 4 groups (n=12), and the other 3 groups were made cholelithiasis model except blank group. Aspirin group and Jinhutongdan recipe group were calculate the stone-formation rate. Serum TNF-α level was detected by ELISA. RESULTS:  (1) 23 active ingredients acted on cholelithiasis through 23 common targets, including EGFR, CCND1, TP53, EGF, IL-6, etc. The KEGG pathway enrichment analysis showed that  13 pathways were related to cholelithiasis. TNF and Isorhamnetin, EGFR and Kaempferol, EGFR and Isorhamnetin, TP53 and beta-sitosterol showed strong binding activity. (2) Animal experiment results: The lithogenesis rate of the model group significantly higher than blank group (P<0.05); The lithogenesis rate of Jinhutongdan recipe was lower than other groups.The serum TNF-α was significantly increased in each group (P<0.01); Compared with  serum TNF-α content in Jinhutongdan group was significantly decreased. CONCLUSION: (1) Jinhutongdan recipe may play a role in the treatment of cholelithiasis by inhibiting inflammation, enhancing immunity,anti tumor, regulating cell proliferation and antioxidation. (2) Jinhutongdan recipe has therapeutic effect on model guinea pigs, the mechanism may be in inhibits inflammatory factors and alleviates inflammatory response by regulating TNF-α expression. 

Key words: network pharmacology, Jinhutongdan, cholelithiasis, TNF-α, anti-Inflammation, anti-tumor