Systematically Explore the Absorbed Constituents and Metabolites in Rat Serum and Urine after Oral Administration and the Potential Mechanisms of <i>Anemarrhenae Rhizoma</i> Against T2DM by Serum Pharmacochemistry Combined with Network Pharmacology

Anemarrhenae Rhizoma (AR), a classical and common traditional Chinese medicine (TCM) herbal, has been broadly used to treat type 2 diabetes mellitus (T2DM) and its complication s in combination with other herbs. Although the hypoglycemic effectiveness of AR has been confirmed in clinic, the chemical constituents responsible for bioactivity of AR in vivo and their potential mechanism of action were still unknown. In this research, A strategy integrated serum pharmacochemistry based on ultra hgh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS) with network pharmacology was applied to identify the absorbed prototype constituents and metabolites of AR in the rat serum and urine after oral administration, as well as investigate anti-T2DM mechanism of AR. As a result, 70 absorbed prototype constituents and 11 metabolites were unambiguously or tentatively identified and further subjected to the pharmacological network construction. 141 therapeutic targets and 18 T2DM-related signaling pathways of the 24 representative absorbed components were collected and generated a components-targets-pathways network. Afterward, 5 key active components and 17 hub targets were identified in terms of the degree values, and the selected key constituents docked excellent with the hub targets. Therefore, the core targets corresponding pathways such as PI3K-Akt, MAPKs, NF-κB, Jak-STAT, etc, were probably closely related to the anti-T2DM effects of AR. It is the first time that the combination of serum pharmacochemistry and network pharmacology were used to perform a systematical investigation on the functional materials basis of AR and its pharmacological mechanisms, which provides a sound scientific evidence for further pharmacology and bioactive material research on AR development.