Immunomodulatory Effect of Shakuyaku (Paeoniae Radix) Extract and Its Use for Preventing Inflammatory Bowel Disease

ABSTRACT Aim Shakuyaku, the root of Paeonia lactiflora , has been used as a traditional medicine for its anti‐inflammatory properties, and paeoniflorin is recognized as its major bioactive monoterpene glycoside responsible for this activity. In this study, we examined the systemic pharmacological effects of Shakuyaku extract through transcriptomic analysis of multiple tissues collected from mice treated with the extract. Methods We performed bulk RNA sequencing on multiple tissues (brain, heart, intestine, kidney, liver, lung, and spleen) collected from mice treated with Shakuyaku extract to investigate its systemic pharmacological effects. To evaluate the preventive effect of Shakuyaku extract on inflammatory bowel disease, mice were pretreated with the extract and subsequently challenged with dextran sodium sulfate (DSS), which induces colitis in mice. Results Bulk RNA sequencing of multiple tissues from mice treated with Shakuyaku extract revealed significant changes in gene expression, particularly in the colon, and highlighted its anti‐inflammatory effects by downregulating the IL‐17/TNF‐α axis, which is critical for the onset of inflammatory bowel disease. In the DSS‐induced colitis model, pretreatment with Shakuyaku extract significantly prevented loss of body weight, reduced disease activity index scores, and improved macroscopic pathology. Mechanistically, treatment with Shakuyaku extract significantly suppressed the upregulation of proinflammatory cytokine mRNAs and reduced the infiltration of neutrophils and inflammatory macrophages in the colons of DSS‐treated mice. Conclusion These results indicate that Shakuyaku extract exerts preventive effects against inflammatory bowel disease through its anti‐inflammatory and immunomodulatory activities.