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Inhibition of Three Diabetes-Related Enzymes by Procyanidins from Lotus (Nelumbo nucifera Gaertn.) Seedpods

Abstract

The inhibitory effects of procyanidins from lotus (Nelumbo nucifera Gaertn.) seedpods on the activities of α-amylase, α-glucosidase and protein tyrosine phosphatase 1B (PTP1B), were studied and compared with those of (+)-catechin, (−)-epicatechin, epigallocatechin gallate (EGCG), procyanidin dimer B2 and trimer C1. The results showed that Lotus procyanidin extract (LPE) significantly inhibited α-amylase, α-glucosidase and PTP1B with IC50 values of 5.5, 1.0, and 0.33 μg/mL, respectively. The inhibition increased with the degree of polymerization and the existence of galloyl or gallocatechin units. Kinetic analysis showed that LPE inhibited α-glucosidase activity in a mixed competitive and noncompetitive mode. Fluorescence quenching revealed that α-glucosidase interacted with LPE or EGCG in an apparent static mode, or the model of “sphere of action”. The apparent static (K) and bimolecular (kq) constants were 4375 M−1 and 4.375 × 1011 M−1 s−1, respectively, for LPE and 1195 M−1 and 1.195 × 1011 M−1 s−1, respectively, for EGCG. Molecular docking analysis provided further information on the interactions of (+)-catechin, (−)-epicatechin, EGCG, B2 and C1 with α-glucosidase. It is hypothesized that LPE may bind to multiple sites of the enzyme through hydrogen bonding and hydrophobic interactions, leading to conformational changes in the enzyme and thus inhibiting its activity. These findings first elucidate the inhibitory effect of LPE on diabetes-related enzymes and highlight the usefulness of LPE as a dietary supplement for the prophylaxis of diabetes.

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Data Availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This research was supported by the Beijing Natural Science Foundation (Grant No. 6212002).

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Contributions

Designed the experiments, Junsong Xiao; Performed the experiments, Jie Xiang; Performed the Molecular docking simulation, Raka Rifat Nowshin and Hua Wu; Performed the analysis of the enzymatic inhibition, Zhiqian Ding and Hua Wu; Performed visualization and analysis, Luocheng Zhang and Jie Xiang; Wrote and revised the paper, Junsong Xiao and Jie Xiang. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Junsong Xiao.

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Xiang, J., Raka, R.N., Zhang, L. et al. Inhibition of Three Diabetes-Related Enzymes by Procyanidins from Lotus (Nelumbo nucifera Gaertn.) Seedpods. Plant Foods Hum Nutr 77, 390–398 (2022). https://doi.org/10.1007/s11130-022-00987-y

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Keywords

  • Nelumbo nucifera Gaertn
  • Procyanidins
  • α-Amylase
  • α-Glucosidase
  • PTP1B
  • Molecular docking