Serum Metabolomics Coupled with Network Pharmacology Strategy to Explore Therapeutic Effects of Scutellaria Baicalensis Georgi on Diabetic Nephropathy

Abstract

Scutellaria baicalensis Georgi ( S. baicalensis ) is a traditional Chinese medicine that has been used in the treatment of diabetes for centuries. Although it has curative effects on diabetic nephropathy (DN), the critical role and mechanisms of S. baicalensis in the prevention and management of DN have not been fully elucidated. Thus, in the current study, metabolomics was integrated with a network pharmacology approach to explore the mechanisms of S. baicalensis against DN. To illustrate the metabolic alterations regulated by S. baicalensis during DN progression, an untargeted serum metabolomics approach using ultra-high- performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was developed. It revealed that 14 serum metabolic biomarkers identified in DN rats were partially reversed by S. baicalensis treatment, which was primarily involved in glycerophospholipid metabolism, arachidonic acid metabolism and retinol metabolism pathways, with 536 extended metabolite-target genes (M-T) interactions observed. Based on network pharmacology analysis, a total of 31 active compounds and 123 compound-target genes (C-T) interactions of S. baicalensis were identified. By integrating M-T with C-T co-network analysis, 18 shared genes were identified as hub targets against DN, including MAPK14, MPO, MMP9, FN1, NOS2 and CASP3, which primarily contributed to biological processes related to inflammatory responses. The molecular docking analysis further verified the interactions between the major active compounds and six predicted proteins encoded by the hub targets, indicating that S. baicalensis may function by targeting inflammatory responses process in DN. Overall, the current work yielded new insights into the molecular mechanisms of active compounds in the action of S. baicalensis against DN progression and suggested a strategy for clarifying the treatment mechanisms of traditional herbal medicines. An UHPLC-Q-TOF-MS based serum metabolomics analysis integrated with a network pharmacology approach was applied to explore the therapeutic mechanisms of Scutellaria baicalensis Georgi ( S. baicalensis ) against diabetic nephropathy. S. baicalensis was observed and verified to function by targeting oxidative stress and inflammatory responses process, thereby modulating renal injury induced by diabetic nephropathy.