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Rapid discovery of potential ADR compounds from injection of total saponins from Panax notoginseng using data-independent acquisition untargeted metabolomics

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Abstract

Injection of total saponins from Panax notoginseng (ISPN) is a modern preparation derived from traditional Chinese medicine (TCM) and is widely applied in the treatment of cardiovascular, cerebrovascular, ophthalmology, and endocrine system diseases. With the increase in the clinical application of ISPN, its adverse drug reactions (ADRs) and related safety issues have attracted much attention. In the present study, a data-independent acquisition (DIA) strategy was proposed to comprehensively characterize the saponins contained in ISPN based on the ultra-high-performance liquid chromatography/quadrupole-Orbitrap MS (UHPLC/Q-Orbitrap MS) platform. As many as 276 saponins were detected, and 250 compounds were identified or tentatively identified based on the retention times and MS/MS data. Furthermore, a metabolomic strategy was utilized to discover the discriminative saponins between normal and ADR batches. The results showed that six saponins, including ginsenoside Rh4, ginsenoside Rk3, ginsenoside Rg5, ginsenoside Rk1, ginsenoside Rg6, and 20(S)-ginsenoside Rh2, were significantly different between the two groups. According to cytotoxicity analysis and degranulation detection of RBL-2H3 cells, ginsenoside Rg5, ginsenoside Rk1, and 20(S)-ginsenoside Rh2 were considered the potential compounds responsible for clinical ADRs, ultimately. In addition, the quantitative analysis showed that the content of these three compounds in ISPN samples with ADRs was generally higher than that in samples without ADRs. This study demonstrated that it is advisable to screen out potential markers related to ADRs for developing the quality standard of ISPN by the integration of untargeted metabolomic analysis and cell biology study, and thus reduce its ADRs in the clinic.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request. Original material is also available upon request.

Code availability

MS-DIAL is an open-source software and readily available to the public.

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Acknowledgements

Many thanks for sampling supportment from The Guangxi Wuzhou Pharmaceutical (Group) Co., Ltd. (Wuzhou, China).

Funding

This study was supported by Important Drug Development Fund, Ministry of Science and Technology of China (2019ZX09201005-002-007), Tianjin Municipal Education Commission Research Project (2017KJ128), and Tianjin Committee of Science and Technology, China (20ZYJDJC00120).

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Authors and Affiliations

  1. State Key Laboratory of Component-based Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, Jinghai District, Tianjin, 301617, People’s Republic of China

    Chenxi Wang, Xu Pang, Tongtong Zhu, Yi Zhang, Tao Wang & Lifeng Han

  2. Beijing Key Laboratory of TCM Basic Research on Prevention and Treatment of Major Disease, Experimental Research Center, China Academy of Chinese Medical Sciences, 16 Nanxiao Road, Dongzhimen, Beijing, 100700, People’s Republic of China

    Shuhua Ma

  3. Guangxi Wuzhou Pharmaceutical (Group) Co., LTD., No.1 Industrial Avenue, Wuzhou Industrial Park, Guangxi, 543002, People’s Republic of China

    Yunfei Liang & Xing Lan

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  1. Chenxi Wang
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Chenxi Wang and Xu Pang contributed equally to this work.

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Wang, C., Pang, X., Zhu, T. et al. Rapid discovery of potential ADR compounds from injection of total saponins from Panax notoginseng using data-independent acquisition untargeted metabolomics. Anal Bioanal Chem 414, 1081–1093 (2022). https://doi.org/10.1007/s00216-021-03734-5

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