###### Abstract  
_Cirsium japonicum_, a traditional herb, exhibits significant anti-inflammatory activity. However, the main components and potential mechanisms of _C. japonicum_ remain unclear. The aim of this study is to investigate the anti-inflammatory mechanism of _Cirsium japonicum_ through network pharmacology and cellular experiments. The effective components of and potential targets for the anti-inflammatory activity of _C. japonicum_ were identified using a traditional Chinese medicine systematic pharmacology database, the TCMSP analysis platform, and the GeneCards database. The drug-component-target-disease network diagram was constructed using Cytoscape 3.8.0 software, while the protein interaction network diagram was created using the STRING database and Cytoscape 3.8.0 software. Gene ontology (GO) enrichment and KEGG pathway enrichment analysis were carried out using the DAVID database. Molecular docking between key targets and active components was constructed with AutoDock 4.2 software to determine the best binding target. The results revealed that 14 active components of _C. japonicum_ targeted 171 anti-inflammatory proteins. GO function enrichment analysis yielded 173 items, while KEGG pathway enrichment analysis identified 48 signaling pathways related to inflammation regulation. Molecular docking showed a strong affinity of sitosterol, stigmasterol, and other components with key targets such as peroxisome proliferatorator-activated receptor \(\alpha\) recombinant protein (PPARA) and cyclooxygenase-2 (PTGS2). Vanillin, one active ingredient of _C. japonicum_, inhibited the release of lipopolysaccharideacharide (LPS)-induced inflammatory factors in RAW264.7 cells. These findings suggest that _C. japonicum_ may exert its anti-inflammatory effects by modulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signal pathway (PI3K-Akt) and apoptin signal pathway, highlighting the multi-component, multi-target, and multi-channel molecular mechanism underlying its anti-inflammatory properties. Finally, the anti-inflammatory effect of vanillin, an effective component of _C. japonicum_, was verified by cell experiments. This study provides a new understanding of the pharmacological mechanisms of _C. japonicum_ in the treatment of inflammatory conditions. _C. elegans_, _C. elegans_, _C. This plant has been the subject of some scientific investigation, particularly regarding its phytochemistry and potential health benefits. Several studies have demonstrated that the aqueous extract of _C. japonicum_ exhibits effective therapeutic potential against infectious jaundice and chronic hepatitis [7]. Additionally, it displays inhibitory activity against _Mycobacterium tuberculosis_, _Neisseria meningitidis_, _Mycobacterium diphtherie_, _Staphylococcus aureus_, _Mycobacterium typhi_, _Mycobacterium partayphi_, and _Mycobacterium anthracis_[8]. Furthermore, it has been found to ameliorate metabolic disorders associated with the steatohepatitis conditions induced by high-fat diets [9]. Aqueous, alkaline, and acidic alcoholic extracts of _C. japonicum_, as well as aqueous extracts of its leaves, have demonstrated antihypertensive effects [10]. Clinical reports have also documented the use of root tablets for hypertension treatment [11]. Additionally, _C. japonicum_ has been reported to enhance immunity, promote lipid metabolism, exhibit diuretic and hepatoprotective properties, enhance ethanol metabolizing enzyme activity, and reduce lipid peroxidation [12]. Furthermore, it also possesses anti-inflammatory, antioxidant, and antitumor activity [13; 14; 15]. Another study demonstrated that _C. japonicum_ flower has potent anti-cancer efficacy by inactivating Aktl in the phosphoinositide 3-kinase/Akt (PI3K/Akt) signaling pathway, which reduces the severity of inflammation in mice and inhibits the expression of apoptosis-related protein [16; 17]. However, the main components of _C. japonicum_ and the potential mechanisms of its anti-inflammatory activities remain unclear.