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Plants provide a rich source of lead compounds for a variety of diseases. A novel approach combining phytochemistry and chemotaxis assays was developed and used to identify and study the mechanisms of action of the active compounds in F. japonica, a medicinal herb traditionally used to treat inflammation. Based on a bioactivity-guided purification strategy, two anthranoids, emodin and physcion, were identified from F. japonica. Spectroscopic techniques were used to characterize its crude extract, fractions and phytochemicals. The crude extract, chloroform fraction, and anthranoids of F. japonica significantly inhibited CXCR4-mediated chemotaxis. Mechanistic studies showed that emodin and physcion inhibited chemotaxis via inactivating the MEK/ERK pathway. Moreover, the crude extract and emodin could prevent or treat type 1 diabetes in non-obese diabetic (NOD) mice. This study illustrates the applicability of a combinational approach for the study of anti-inflammatory medicine and shows the potential of F. japonica and its anthranoids for anti-inflammatory therapy.