Identification of Q-Markers from Hedan Tablet by employing "spider-web" mode and taking compounds' hepatotoxicity into account

Danni Wang; Jiamin Ding; Xiafei Feng; Xin Chai; Jing Yang; Chunlei Liu; Yingzi Zeng; Wanhui Zhou; Yuefei Wang

doi:10.1016/j.chmed.2021.08.007

Identification of Q-Markers from Hedan Tablet by employing "spider-web" mode and taking compounds' hepatotoxicity into account

Chin Herb Med. 2022 Aug 29;14(4):612-621. doi: 10.1016/j.chmed.2021.08.007. eCollection 2022 Oct.

Authors

Danni Wang¹, Jiamin Ding¹, Xiafei Feng², Xin Chai¹, Jing Yang¹, Chunlei Liu³, Yingzi Zeng³, Wanhui Zhou³, Yuefei Wang¹

Affiliations

¹ State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
² Foreign Language College, Donghua University, Shanghai 201620, China.
³ Shandong Wohua Pharmaceutical Technology Co., Ltd., Weifang 261000, China.

Abstract

Objective: Due to the complicated compounds and the synergistic effect of multi-compounds, the quality control and assessment of Chinese materia medica (CMM) encounters a great challenge about how to identify the key compounds, which are directly correlated with its efficacy and safety. On the guidance of study on quality marker (Q-Marker), identification of Q-Markers was performed from Hedan Tablet (HDT) by the aid of the "spider-web" mode and hepatotoxicity evaluation derived from our previous researches and literatures.

Methods: By the established ultra performance liquid chromatography with photodiode array detector (UPLC-PDA) method, online UPLC-DPPH· and offline antioxidant assay, 21 candidate compounds of HDT were systematically investigated and comprehensively evaluated by the "spider-web" mode for them properties of Q-Marker based on "content-stability-activity". In addition, the Q-Markers related with hepatotoxicity based on our previous researches and literatures were identified.

Results: Salvianolic acid B (SaB), quercetin-3-O-glucuronide (Qug), isoquercitrin (IQ) and hyperoside (Hyp) were adopted as the preferable Q-Markers of HDT according to the shaded area (A) of tested compounds in "spider-web" mode. Psoralen (Ps), isopsoralen (IP), psoralenoside (PO) and isopsoralenoside (IPO) were also strongly recommended as Q-Markers closely related with safety by considering hepatotoxicity of the accumulated Ps and IP and conversion between glycoside (PO and IPO) and aglycone (Ps and IP).

Conclusion: This study provided scientific evidence for quality control and assessment of HDT, and also provided a meaningful reference for application of Q-Markers in CMM.

Keywords: Hedan Tablet; Q-Markers; hepatotoxicity; quality control; “Spider-web” mode.