Based on network pharmacology and molecular docking techniques to predict the material basis and toxicity mechanism of Chuanlianzi（Toosendan Fructus）hepatotoxicity and to validate the reducing effects after processing in combination with in vivo and in vitro experiments.

The toxic components and targets of Chuanlianzi（Toosendan Fructus）were collected using the systematic pharmacology analysis platform of traditional Chinese medicine（TCMSP）and the Swiss Target Prediction database，respectively. Liver injury related targets were obtained through GeneCards and OMIM databases. After the common targets were screened by Venny diagram，PPI analysis was carried out by STRING database，and enrichment analysis on GO function and KEGG pathway were conducted to predict their possible toxicity mechanisms. Molecular docking validation and visualization of key components of Chuanlianzi（Toosendan Fructus）hepatotoxicity with key protein binding sites and binding effects were performed using AutoDockTools and PyMOL software. In vivo experiments were conducted to compare the magnitude of acute hepatotoxicity of different processed products of Chuanlianzi（Toosendan Fructus）in mice by detecting the viability of alanine aminotransferase（ALT）and aspartate aminotransferase（AST）in serum and observing the pathologic morphology of liver tissues with HE staining method and to determine the levels of superoxide dismutase（SOD），malondialdehyde（MDA），glutathione（GSH），and glutathione peroxidase（GSH-P_X）and analyzed the reasons for the differences in the hepatotoxicity of different processed products of Chuanlianzi（Toosendan Fructus）in mice from the perspective of oxidative damage.

Network pharmacology showed that Chuanlianzi（Toosendan Fructus）hepatotoxicity components were melianone，Toosendanin and Nimbolin A，and its core targets for liver injury were TP53，IL-6 and CASP3. GO enrichment was analyzed to the biological processes，such as positive regulation of transcription and gene expression，negative regulation of the apoptotic process，and inflammatory response，cellular components，such as extracellular region，outer mitochondrial membrane，mitochondria，protein binding，protein homodimerization activity，enzyme binding and other molecular functions. KEGG pathway analysis screened TNF，PI3K-Akt，IL-17，HIF-1，apoptosis and other key signaling pathways of Chuanlianzi（Toosendan Fructus）-induced hepatotoxicity. The molecular docking results showed that the main toxic components of Chuanlianzi（Toosendan Fructus）could bind well to the core targets. In vivo experimental results showed that compared with the raw Chuanlianzi（Toosendan Fructus），the vinegar-processing，stir-frying to brown and salt-processing products all significantly reduced the activities of ALT and AST in the serum of mice（P<0.05），and the wine-processing product showed a significant increase in both ALT and AST. HE staining showed that the vinegar-processing product，stir-frying to brown and salt-processing products reduced the infiltration of inflammatory cells in the liver tissues and apoptosis of hepatocytes of mice，which suggested that Chuanlianzi（Toosendan Fructus）had the effect of alleviating liver injury after processing. This suggested that Chuanlianzi（Toosendan Fructus）had the effect of reducing liver injury，but the hepatotoxicity of the wine-processing product was greater than that of the raw product. This result suggested that the mechanism of liver toxicity induced by raw Chuanlianzi（Toosendan Fructus）in mice was related to the disruption of their antioxidant defense system，reduced ability to scavenge free radicals and subsequent excessive accumulation of free radicals in the body，which induced cell membrane lipid peroxidation.

The vinegar-processing，stir-frying to brown and salt-processing products may reduce hepatotoxicity by altering the effects of Chuanlianzi（Toosendan Fructus）on hepatotoxic targets such as TP53，IL-6 and CASP3，reducing inflammatory responses and inhibition of cell membrane lipid peroxidation，but the wine-processing product is more toxic and should be avoided in clinical practice.