Exploring the therapeutic effects of Zingiberis Rhizoma Preparatum (Pao-Jiang) against DSS-induced ulcerative colitis in mice by metabolomics-guided analysis

Abstract

Zingiberis Rhizoma Recens (Sheng-Jiang) is a kind of edible and medicinal plant resource in China. Both Zingiberis Rhizoma Recens and its dried form, Zingiberis Rhizome (Gan-Jiang), have been widely used in traditional Chinese medicine prescriptions for the treatment of digestive disease. Based on traditional Chinese medicine (TCM) theory, the heat-processed product of Zingiberis Rhizome, Zingiberis Rhizoma Preparatum (Pao-Jiang) is more effective in arresting bleeding and alleviating pain, which is suitable for relieving the classic symptoms of ulcerative colitis (UC), a chronic relapsing idiopathic inflammation of the gastrointestinal tract. In present study, the pharmacological evaluation combined with metabolomics-guided analysis were applied to explore the intestinal protective effects and mechanism of Pao-Jiang on dextran sulfate sodium (DSS)-induced colitis mouse model. The pathological and biochemical tests showed that the water and alcohol extracts of Gan-Jiang and Pao-Jiang could reduce the disease activity index (DAI) and colon tissue damage, inhibit the secretion of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and leukocyte-mediated interleukin-1β and 6 (IL-1β and IL-6), and alleviate abnormal histopathological changes of UC mice in various degrees. The alcohol extracts of Pao-Jiang showed relatively better effects. Untargeted and targeted metabolomic profiling revealed that the alcohol extracts of Pao-Jiang can significantly reverse the UC induced metabolic perturbations, especially focuses on bile acids metabolism, eicosanoids and phospholipids metabolism. Furthermore, comparative chemical profiling and molecular docking analysis indicated that the contents of shogaols and gingerdiones in Pao-Jiang increased after heating processing and may contribute to the regulatory effects of bile acid synthesis and transport by interacting with CYP7A1, BSEP and IBABP, and promote the anti-inflammatory effects. This study expands our knowledge about potential function of Gan-Jiang and Pao-Jiang, and are of significance for providing insights into the scientific connotation of traditional Chinese medicine processing methods.