Identifying The Mechanisms Of Tian Jing Yi Xue Decoction Against Drug Induced Liver Injury By Network Pharmacology

Background:With the gradual emergence of drug adverse reactions,drug induced liver injury,this global health problem is increasingly worthy of attention.For drug induced liver injury,Tian Jing Yi Xue Decoction has good clinical efficacy,however,its lurking mechanisms were unknown.Purpose:This experiment’s purpose is to explore the mechanisms and effective components of Tian Jing Yi Xue Decoction in the treatment of drug induced liver injury.Methods:Tian Jing Yi Xue Decoction was used to treat the model of H₂O₂induced Hep G2 cell injury and the CCl₄ induced liver injury in SD rats.HPLC-MS was used to qualitatively analyze the components of Tian Jing Yi Xue Decoction.Network pharmacology was used to predict the mechanisms and effective components of Tian Jing Yi Xue Decoction in the treatment of drug induced liver injury.Finally,（western blot、IHC、q RT-pcr、ELISA） experimental studies were used to verify the partial mechanisms of Tian Jing Yi Xue Decoction in the treatment of drug induced liver injury.Results:In the model of treating H₂O₂ induced Hep G2 cell injury by Tian Jing Yi Xue Decoction,2mg/m L of Tian Jing Yi Xue Decoction could significantly reduce the content of ALT,AST,ALP in the culture medium,which indicated that Tian Jing Yi Xue Decoction could effectively treat drug induced liver injury in vitro.In the model of treating CCl₄ induced liver injury in SD rats by Tian Jing Yi Xue Decoction,Tian Jing Yi Xue Decoction could significantly reduce the content of ALT,ALP,MDA and increase the content of SOD in the serum;at the same concentration（50mg/m L）,the results of HE staining and Masson staining further confirmed that the efficacy of Tian Jing Yi Xue Decoction in the treatment of drug induced liver injury was better than silymarin.Qualitative analysis by HPLC-MS,network pharmacology prediction,experimental studies’verification,step by step,proved that Tian Jing Yi Xue Decoction（77 effective components）played a role in treating drug induced liver injury by inhibiting the PI3K/AKT/m TOR signaling pathway and anti-inflammatory action,and speculated that the most important components of Tian Jing Yi Xue Decoction in the treatment of drug induced liver injury were quercetin,apigenin,luteolin,etc.Prospect:Due to the multi-components characteristics of Tian Jing Yi Xue Decoction,for drug induced liver injury,it may play roles in other signaling pathways（HIF-1 signaling pathway,Fox O signaling pathway,Prolactin signaling pathway,etc.）and other ways（response to hormone,regulation of mi RNA metabolic process,etc.）;it still has the potential to be used as the first choice drug（hepatitis B,liver cancer,etc.）or auxiliary drug（diabetes,hypertension,Alzheimer’s disease,etc.）in the face of other diseases or the complications of multiple diseases.