Revealing the potential pharmacological mechanism of traditional Chinese medicine by integrating metabolite profiling of a Q-marker and network pharmacology, prim-O-glucosylcimifugin as an example

Along with definite clinical effects, traditional Chinese medicine (TCM) has increasingly gained worldwide attention. Quality control marker (Q-marker) is always used to confirm the primary effects of herbs or TCM. Thus, the characterization of the metabolism features and subsequently induced effects are essential to reveal the functional consequences. In this work, a strategy by integrating metabolite profiling of a Q-marker and network pharmacology was proposed and applied to explore the potential function of herbs, and prim-O-glucosylcimifugin, the Q-marker of Radix Saposhnikoviae, was used as an example. As a result, 35 metabolites were characterized in rats' plasma, urine, feces, heart, liver, spleen, lung, kidney, and brain. Among them, M13/M17/M20/M23/M24/M28 were the primary metabolites, and 23 metabolites were reported for the first time. It was found that major metabolic pathways of prim-O-glucosylcimifugin were hydroxylation, dehydrogenation, hydrogenation and glucuronidation. In addition to the above metabolic reactions, methylation, hydrogenation, glycosylation, isomerization, sulfation, and other S-conjunctions were found in prim-O-glucosylcimifugin for the first time. Meanwhile, targets of prim-O-glucosylcimifugin and its major metabolites targeted additional 125 targets with functions of MAPK signaling pathway, proteoglycans in cancer, pathways in cancer, bladder cancer, colorectal cancer, serotonergic synapse and natural killer cell-mediated cytotoxicity. Among them, the depression of inflammation by MAPK signaling pathway might be the core mechanism for prim-O-glucosylcimifugin to treat respiratory tract infections. The above results provided vital information for understanding the metabolism and functional mechanism of prim-O-glucosylcimifugin in the treatment of respiratory tract infections, and a new insight for revealing the pharmacological mechanism of the complex system was also provided.