Skip to main content

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


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.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Data Availability

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


  1. Forbes JM, Cooper ME (2013) Mechanisms of diabetic complications. Physiol Rev 93(1):137–188.

    CAS  Article  PubMed  Google Scholar 

  2. Balaji R, Duraisamy R, Kumar M (2019) Complications of diabetes mellitus: a review. Drug Invent Today 12(1):98–103

    Google Scholar 

  3. Milella L, Milazzo S, De Leo M et al (2016) α-Glucosidase and α-amylase inhibitors from Arcytophyllum thymifolium. J Nat Prod 79(8):2104–2112.

    CAS  Article  PubMed  Google Scholar 

  4. Tamrakar AK, Maurya CK, Rai AK (2014) PTP1B inhibitors for type 2 diabetes treatment: a patent review (2011–2014). Expert Opin Ther Pat 24(10):1101–1115.

    CAS  Article  PubMed  Google Scholar 

  5. Ferhati X, Matassini C, Fabbrini MG et al (2019) Dual targeting of PTP1B and glucosidases with new bifunctional iminosugar inhibitors to address type 2 diabetes. Bioorg Chem 87:534–549.

    CAS  Article  PubMed  Google Scholar 

  6. Hossain U, Das AK, Ghosh S, Sil PC (2020) An overview on the role of bioactive α-glucosidase inhibitors in ameliorating diabetic complications. Food Chem 145:111738.

  7. Mahmood N (2016) A review of α-amylase inhibitors on weight loss and glycemic control in pathological state such as obesity and diabetes. Comp Clin Path 25(6):1253–1264.

    CAS  Article  Google Scholar 

  8. Mendes NF, Castro G, Guadagnini D et al (2017) Knocking down amygdalar PTP1B in diet-induced obese rats improves insulin signaling/action, decreases adiposity and may alter anxiety behavior. Metabolism 70:1–11.

    CAS  Article  PubMed  Google Scholar 

  9. Abrahão SA, Pereira RGFA, de Sousa RV, Lima AR, Crema GP, Barros BS (2013) Influence of coffee brew in metabolic syndrome and type 2 diabetes. Plant Foods Hum Nutr 68(2):184–189.

    CAS  Article  PubMed  Google Scholar 

  10. Carmelo Luna FJ, Mendoza Wilson AM, Balandrán Quintana RR (2020) Antiradical and chelating ability of (+)-catechin, procyanidin B1, and a procyanidin-rich fraction isolated from brown sorghum bran. Nova Scientia 12(24).

  11. Dudek MK, Gliński VB, Davey MH, Sliva D, Kaźmierski S, Gliński JA (2017) Trimeric and tetrameric A-type procyanidins from peanut skins. J Nat Prod 80(2):415–426.

    CAS  Article  PubMed  Google Scholar 

  12. Liu M, Xie H, Ma Y et al (2020) High performance liquid chromatography and metabolomics analysis of tannase metabolism of gallic acid and gallates in tea leaves. J Agric Food Chem 68(17):4946–4954.

    CAS  Article  PubMed  Google Scholar 

  13. Rue EA, Rush MD, van Breemen RB (2018) Procyanidins: a comprehensive review encompassing structure elucidation via mass spectrometry. Phytochem Rev 17(1):1–16.

    CAS  Article  PubMed  Google Scholar 

  14. Bhupathiraju SN, Pan A, Manson JE et al (2014) Changes in coffee intake and subsequent risk of type 2 diabetes: three large cohorts of US men and women. Diabetologia 57(7):1346–1354.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Jiawei F, Hairong L, Wang J et al (2021) Procyanidin B2 improves endothelial progenitor cell function and promotes wound healing in diabetic mice via activating Nrf2. J Cell Mol Med 25(2):652–665.

    CAS  Article  Google Scholar 

  16. Chen Y, Tang S, Chen Y et al (2019) Structure-activity relationship of procyanidins on advanced glycation end products formation and corresponding mechanisms. Food Chem 272:679–687.

    CAS  Article  PubMed  Google Scholar 

  17. Punia BS, Kyle D, Manoj K et al (2022) A comprehensive review on lotus seeds (Nelumbo nucifera Gaertn.): nutritional composition, health-related bioactive properties, and industrial applications. J Funct Foods 89:104937.

  18. Xiao J-S, Xie B-J, Cao Y-P et al (2012) Characterization of oligomeric procyanidins and identification of quercetin glucuronide from lotus (Nelumbo nucifera Gaertn.) seedpod. J Agric Food Chem 60(11):2825–2829.

  19. Ling Z-Q, Xie B-J, Yang E-L (2005) Isolation, characterization, and determination of antioxidative activity of oligomeric procyanidins from the seedpod of Nelumbo nucifera Gaertn. J Agric Food Chem 53(7):2441–2445.

    CAS  Article  PubMed  Google Scholar 

  20. Xiao J-S, Liu L, Wu H et al (2008) Rapid preparation of procyanidins B2 and C1 from granny smith apples by using low pressure column chromatography and identification of their oligomeric procyanidins. J Agric Food Chem 56(6):2096–2101.

    CAS  Article  PubMed  Google Scholar 

  21. Rodríguez-Pérez C, García-Villanova B, Guerra-Hernández E et al (2019) Grape seeds proanthocyanidins: an overview of in vivo bioactivity in animal models. Nutrients 11(10):2435.

  22. Wei M, Chai WM, Yang Q et al (2017) Novel insights into the inhibitory effect and mechanism of proanthocyanidins from Pyracantha fortuneana fruit on α-glucosidase. J Food Sci 82(10):2260–2268.

    CAS  Article  PubMed  Google Scholar 

  23. Zhou P, Zhang L, Li W et al (2018) In vitro evaluation of the anti-digestion and antioxidant effects of grape seed procyanidins according to their degrees of polymerization. J Funct Foods 49:85–95.

    CAS  Article  Google Scholar 

  24. Gu Y, Hurst WJ, Stuart DA, Lambert JD (2011) Inhibition of key digestive enzymes by cocoa extracts and procyanidins. J Agric Food Chem 59(10):5305–5311.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. Chiba S (1997) Molecular mechanism in α-glucosidase and glucoamylase. Biosci Biotechnol Biochem 61(8):1233–1239.

    CAS  Article  PubMed  Google Scholar 

  26. Kong F, Qin Y, Su Z et al (2018) Optimization of extraction of hypoglycemic ingredients from grape seeds and evaluation of α-glucosidase and α-amylase inhibitory effects in vitro. J Food Sci 83(5):1422–1429.

    CAS  Article  PubMed  Google Scholar 

  27. Cao J, Yan S, Xiao Y et al (2022) Number of galloyl moiety and intramolecular bonds in galloyl-based polyphenols affect their interaction with alpha-glucosidase. Food Chem 367:129846.

    CAS  Article  PubMed  Google Scholar 

  28. Soares S, Mateus N, De Freitas V (2007) Interaction of different polyphenols with bovine serum albumin (BSA) and human salivary α-amylase (HSA) by fluorescence quenching. J Agric Food Chem 55(16):6726–6735.

    CAS  Article  PubMed  Google Scholar 

  29. Sun L, Song Y, Chen Y et al (2021) The galloyl moiety enhances the inhibitory activity of catechins and theaflavins against α-glucosidase by increasing the polyphenol-enzyme binding interactions. Food Funct 12(1):215–229.

    CAS  Article  PubMed  Google Scholar 

  30. Siebert KJ, Troukhanova NV, Lynn PY (1996) Nature of polyphenol-protein interactions. J Agric Food Chem 44(1):80–85.

    CAS  Article  Google Scholar 

  31. Gonçalves R, Mateus N, De Freitas V (2011) Inhibition of α-amylase activity by condensed tannins. Food Chem 125(2):665–672.

    CAS  Article  Google Scholar 

  32. Li M, Jia X, Yang J et al (2012) Effect of tannic acid on properties of soybean (Glycine max) seed ferritin: a model for interaction between naturally-occurring components in foodstuffs. Food Chem 133(2):410–415.

    CAS  Article  PubMed  Google Scholar 

  33. Wu H, Zeng W, Chen L et al (2018) Integrated multi-spectroscopic and molecular docking techniques to probe the interaction mechanism between maltase and 1-deoxynojirimycin, an α-glucosidase inhibitor. Int J Biol Macromol 114:1194–1202.

    CAS  Article  PubMed  Google Scholar 

  34. Kovalev IS, Taniya OS, Kopchuk DS et al (2018) 1-Hydroxypyrene-based micelle-forming sensors for the visual detection of RDX/TNG/PETN-based bomb plots in water. New J Chem 42(24):9864–19871.

    Article  Google Scholar 

  35. Dai T, Li T, He X et al (2020) Analysis of inhibitory interaction between epigallocatechin gallate and alpha-glucosidase: a spectroscopy and molecular simulation study. Spectrochim Acta Part A: Mol Biomol Spectrosc 230:118023.

    CAS  Article  Google Scholar 

Download references


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

Author information

Authors and Affiliations



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.

Corresponding author

Correspondence to Junsong Xiao.

Ethics declarations

Ethics Approval

Not applicable.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Conflict of Interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information


(PDF 218 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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).

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


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