Drug Design, Development and Therapy (Mar 2023)
Therapeutic Mechanism of Baicalin in Experimental Colitis Analyzed Using Network Pharmacology and Metabolomics
Abstract
Qi Wu,1,* Xingxing Wu,1,* Mao Wang,2,* Kexin Liu,1 Yuge Li,1 Xiaoyu Ruan,1 Lin Qian,1 Lingchang Meng,3 Zhiting Sun,3 Lei Zhu,1 Jing Wu,3 Genglin Mu3 1Gastroenterology Department, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Ethics Committee, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3Institute of Chinese Medicine, Nanjing University, Nanjing Drum Tower Hospital, Drum Tower Clinical Medicine College of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Wu; Genglin Mu, Nanjing Drum Tower Hospital, Drum Tower Clinical Medicine College of the Nanjing University of Chinese Medicine, 321, Zhongshan Road, Nanjing, Jiangsu, People’s Republic of China, Tel +86 13451825475, Email [email protected]; [email protected]: Baicalin is an important active flavonoid isolated from the roots of Scutellaria baicalensis (S. baicalensis), a well-known traditional Chinese herb used in treating inflammatory bowel disease (IBD). The objectives of this study were to assess the potential benefit of baicalin in experimental colitis, as well as to investigate metabolic biomarkers of experimental colitis in conjunction with network pharmacology.Methods: Using a widely utilized network pharmacology technique, baicalin’s targets and pathways were predicted. Simultaneously, experimental colitis was induced by intrarectal administration of TNBS. Histopathology examinations were performed to confirm pathological changes. Plasma samples were examined by using an untargeted metabolomics technique based on ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) to screen differential metabolites and associated metabolic pathways. Additionally, network pharmacology and integrated analysis of metabolomics were used to identify the primary targets.Results: Through network pharmacology research, tumor necrosis factor (TNF), interleukin 6 (IL6), serine/threonine-protein kinase (AKT1), and other 7 proteins were found to be the main targets of baicalin against IBD. The untargeted metabolomics results showed that 47 metabolites in glycerophospholipids and sphingolipid metabolism were involved as key pathways in the experimental colitis model group. 19 metabolites, including Sphingomyelin (SM d42:2, SM d42:1, SM d34:1), Lysophosphatidic acids (LPA 18:4), 1-Palmitoylglycerophosphocholine, and 17(18)-EpETE were demonstrated as key metabolites for baicalin to exert effects. Moreover, udp-glucose ceramide glucosyltransferase (UGCG), sphingomyelin synthase 1 (SGMS1), and sphingosine kinase (SPHK1) were predicted as sphingolipids-linked targets of baicalin against experimental colitis by integrative analysis.Conclusion: Based on these results, it implies that sphingolipid metabolism and sphingolipid signaling pathway might be acted as therapeutic mechanism for baicalin against experimental colitis.Keywords: baicalin, inflammatory bowel disease, sphingolipid metabolism, metabolomics, network pharmacology, inflammation
