A Novel System Strategy for Quality Marker Screen of Classical Prescriptions: Taking Yiguan Jian as a Case Study

Herbal prescriptions are notable for pleotropic efficacies induced by sophisticated constituents, which greatly challenge drug consistence in clinics. Traditional approaches to monitor quality fluctuations have absorbed detection techniques but fail to reflect pharmacological benefits of herbal products, hence calling an elevating view of quality marker (QM) for systematic monitoring with integrated multidisciplinary affairs. This study aimed to explore systems pharmacology-guided QMs of Yiguan Jian (YGJ) for improving multilayered quality control systems. The high throughput methods including chemoinformatic and compound-target based network pharmacology approaches were employed to discover those QMs of both specificity and evidence-supporting pharmacological properties. The filtrated QMs were deposited in Orbitrap mass spectrometry (MS) qualitative analysis and their contents were determined in a rapid electrospray ionization (ESI)- MS/MS analysis. The whole chemical profiles were analyzed by ultra pressure liquid chromatography (UPLC)- diode array detector (DAD) fingerprint analyses while the antioxidant abilities were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing ability of plasma (FRAP) assays. In the results, 13 QMs were qualitatively identified and quantified in YGJ samples. Among the QMs, 9 indicators were cyclooxygenase 2 (COX2) inhibitors with a range of half maximal inhibitory concentration (IC50) from 0.49 to 3.30 μM. Contributions of the 13 QMs to the total antioxidant properties were assessed, as 3 phenylpropanoid glucosides (Acteoside, Isoacteoside, and Echinacoside), and 1 flavonoid glucoside (Rutin) indicated their large benefits. The chemical profiles of 12 batches of YGJ samples were supervised by the UPLC-DAD fingerprint analysis. In this study, we established a comprehensive platform to determine systems pharmacology-supporting QMs of YGJ that were given specificity, compatibility, detective property, and bioactive ability. This study will present new insights on the holistic quality control system of herbal formulae and their pharmaceuticals in future.