Ipomoea pes-caprae (L.) R. Br (Convolvulaceae) is a commonly used marine traditional Chinese medicine in the southern coastal areas of China. It has been widely used to treat rheumatoid arthritis, but its effective substances and antirheumatoid arthritis mechanism remain ambiguous. Hence, in this study, the chemical profile and absorbed ingredients of Ipomoea pes-caprae were elucidated by ultra-performance liquid chromatography-mass spectrometry. Moreover, targeted network pharmacology was used to clarify the mechanism of action of Ipomoea pes-caprae in treating rheumatoid arthritis. Finally, 23 compounds were identified in the aqueous extracts of Ipomoea pes-caprae and 12 absorbed ingredients were detected in rats' plasma. These 12 absorbed ingredients might be the essential effective substances of Ipomoea pes-caprae. The tissue distributions of 3 absorbed ingredients in rats were successfully analyzed. The targeted network pharmacological analysis results indicated that the regulation of inflammatory reaction, immune response, cell proliferation, and apoptosis were the critical mechanism of Ipomoea pes-caprae against rheumatoid arthritis. This study successfully clarified the effective substances and potential mechanisms of Ipomoea pes-caprae in treating rheumatoid arthritis. The results of this research could provide a valuable reference for further scientific research and clinical application.Article Related Abbreviations: AIA, adjuvant-induced arthritis; CFA, complete Freund's adjuvant; CYP450, cytochrome P450; FLSs, fibroblast-like synoviocytes; KEGG, Kyoto Encyclopedia of Genes and Genomes; RA, rheumatoid arthritis; TNF, tumor necrosis factor; UPLC Q-TOF-MS, ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry; UPLC-TQ-MS, ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry.

As an important Chinese medicine decoction, Wu‐tou decoction has been used to treat rheumatic arthritis for more than a thousand years. We previously reported that the Wu‐tou decoction could change the urinary and serum metabolites in adjuvant‐induced arthritis rats significantly. The purpose of this research was to confirm the potential biomarkers obtained by previous non‐targeted metabolomics study through quantitative analysis by liqui chromatography with tandem mass spectrometry, in the meantime, to further study the effective material basis of Wu‐tou decoction. Firstly, the important compounds in the tryptophan metabolism pathway, the arginine and proline metabolism pathway, the amino acid metabolism pathway, the tricarboxylic acid cycle, the vitamin B6 metabolism pathway, and the phenylalanine metabolism pathway, which were identified as potential biomarkers in previous study, were selected for quantitative analysis. Then the linearity, limit of detection, limit of quantification, selectivity, accuracy, precision, stability, recovery, and matrix effect of the quantitative method were examined. Finally, ten and eighteen metabolites were quantitatively analyzed in the serum and urine, respectively. The results showed that seven out of ten serum potential biomarkers and ten out of eighteen urine potential biomarkers were confirmed as real biomarkers. This research provides a powerful reference for the study on effective material basis of Wu‐tou decoction.