Yupingfeng granules (YPFG) were isolated from a traditional Chinese medicine (TCM) formulation composed of three herbs (Astragali Radix, Atractylodis Macrocephalae Rhizoma, and Saposhnikoviae Radix). This formulation is used in TCM to tonify qi, and it can help strengthen exterior and reduce sweating. Nevertheless, the active components of YPFG remain unclear. In this study, the chemical constituents of YPFG were systematically characterized by ultra-performance liquid chromatography coupled with electrospray ionization/ quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS). Fifty-eight compounds, namely, 20 flavonoids, 19 saponins, nine organic acids, four volatile coumarins, three lactones, one alkaloid, and two other components, were identified. In addition, the constituents of YPFG with the potential for in vivo bioactivities following oral administration were investigated in Sprague-Dawley rats. Thirteen compounds, namely, 11 flavonoid-related and 2 saponin-related components, were detected in rat plasma. After enriching flavonoids and saponins in YPFG by extraction, the extracts and YPFG were administrated to immunosuppressed rats, respectively. Plasma samples were analyzed by UPLC-ESI-Q-TOF-MS, and principal component analysis (PCA) confirmed that the extracts had similar effects to YPFG. This method could discover active ingredients in YPFG quickly and provide a scientific basis for quality control and mechanism research. K E Y W O R D S absorbed components in rat plasma, active components, chemical profiling, principal component analysis, UPLC-ESI-Q-TOF-MS, Yupingfeng granules 1 | INTRODUCTION Yupingfeng (YPF) has been used as an herbal medicine in China for centuries. YPF was first recorded in Dan xi xin fa, 1 which is an ancient book written by Zhenheng Zhu during the Yuan dynasty. YPF, composed of Astragali Radix, Atractylodis Macrocephalae Rhizoma, and Saposhnikoviae Radix, shows excellent activities including in tonifying qi, strengthening exterior, and reducing sweating. Clinically, YPF is often used to treat recurrent common cold, 2 asthmatic bronchitis, 3 allergic rhinitis, 4 and chronic urticaria, 5 all of which are often caused by immune disorders. Recent studies have shown that YPF granules (YPFG) can improve low thymus and spleen function caused by dexamethasone (Dex). Treatment with YPFG restored lymphocytic activity in Dex-treated mice back to the normal level and inhibited Dex-induced apoptosis of lymphocytes. YPFG mitigated the low levels of CD4(+)/CD8(+) caused by Dex and upregulated Dex
