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Ligand-targeted fishing of α-glucosidase inhibitors from Tribulus terrestris L. based on chitosan-functionalized multi-walled carbon nanotubes with immobilized α-glucosidase

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Abstract

α-Glucosidase inhibitors in natural products are one of the promising drugs for the treatment of type 2 diabetes. However, due to the complexity of the matrix, it is challenging to comprehensibly clarify the specific pharmacodynamic substances. In this study, a novel high-throughput inhibitor screening strategy was established based on covalent binding of α-glucosidase on chitosan-functionalized multi-walled carbon nanotubes coupled with high-resolution mass spectrometry. The synthesized MWCNTs@CS@GA@α-Glu was characterized by TEM, SEM, FTIR, Raman, and TG. Performance studies showed that the microreactor exhibited stronger thermostability and pH tolerance than that of the free one while maintaining its inherent catalytic activity. Feasibility study applying a model mixture of known α-glucosidase ligand and non-ligands indicated the selectivity and specificity of the system. By integrating ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-QTOF-MS) with ion mobility mass spectrometry (IMS), 15 ligands were obtained and tentatively identified from Tribulus terrestris L., including 8 steroidal saponins, 4 flavonoids, and 3 alkaloids. These inhibitors were further validated by in vivo experiments and molecular docking simulation.

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Funding

This work was supported by the National Nature Science Foundation of China (No. 81273952) and the Science and the Youth Innovation Promotion Association of CAS (Grant No. 2019227).

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Authors and Affiliations

  1. State Key Laboratory of Electroanalytical Chemistry, National Center of Mass Spectrometry in Changchun and Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China

    Xin Meng, Hou Zong, Zhong Zheng, Junpeng Xing, Zhiqiang Liu, Fengrui Song & Shu Liu

  2. School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China

    Xin Meng, Fengrui Song & Shu Liu

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  1. Xin Meng
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  2. Hou Zong
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  3. Zhong Zheng
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Correspondence to Shu Liu.

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Animal experiments were approved by the Animal Ethics Committee of Changchun Institute of Applied Chemistry (approval number: 2021-39), and were performed in compliance with the NIH guide for the care and use of laboratory animals.

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Meng, X., Zong, H., Zheng, Z. et al. Ligand-targeted fishing of α-glucosidase inhibitors from Tribulus terrestris L. based on chitosan-functionalized multi-walled carbon nanotubes with immobilized α-glucosidase. Anal Bioanal Chem 415, 2677–2692 (2023). https://doi.org/10.1007/s00216-023-04666-y

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