Skip to main content
Log in

Kinetics Analysis of the Inhibitory Effects of Alpha-Glucosidase and Identification of Compounds from Ganoderma lipsiense Mycelium

  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

The studies on natural compounds to diabetes mellitus treatment have been increasing in recent years. Research suggests that natural components can inhibit alpha-glucosidase activities, an important strategy in the management of blood glucose levels. In this work, for the first time in the literature, the compounds produced by Ganoderma lipsiense extracts were identified and evaluated on the inhibitory effect of these on alpha-glucosidase activity. Four phenolic compounds were identified by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) to crude extract from G. lipsiense grown in red rice medium (RCE) and synthetic medium (SCE), being syringic acid identified in both extracts. Gas chromatography-mass spectrometry (GC-MS) analysis showed fatty acids and their derivatives, terpene, steroid, niacin, and nitrogen compounds to SCE, while RCE was rich in fatty acids and their derivatives. Both extracts demonstrated alpha-glucosidase inhibition (RCE IC50 = 0.269 ± 8.25 mg mL−1; SCE IC50 = 0.218 ± 9.67 mg mL−1), and the purified hexane fraction of RCE (RHEX) demonstrated the highest inhibition of enzyme (81.1%). Studies on kinetic inhibition showed competitive inhibition mode to RCE, while SCE showed uncompetitive inhibition mode. Although the inhibitory effects of RCE and SCE were satisfactory, the present findings identified some unpublished compounds to G. lipsiense in the literature with important therapeutic properties.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Yin, Z., Zhang, W., Feng, F., Zhang, Y., & Kang, W. (2014). α-Glucosidase inhibitors isolated from medicinal plants. Food Science and Human Wellness, 3, 136–174. https://doi.org/10.1016/j.fshw.2014.11.003.

    Article  Google Scholar 

  2. Del Valle, P., Martínez, A. L., Figueroa, M., Raja, H. A., & Mata, R. (2016). Alkaloids from the fungus Penicillium spathulatum as α-glucosidase inhibitors. Planta Medica, 82(14), 1286–1294. https://doi.org/10.1055/s-0042-111393.

    Article  CAS  PubMed  Google Scholar 

  3. Wang, K., Bao, L., Ma, K., Zhang, J., Chen, B., Han, J., Ren, J., Luo, H., & Liu, H. (2017). A novel class of α-glucosidase and HMG-CoA reductase inhibitors from Ganoderma leucocontextum and the anti-diabetic properties of ganomycin I in KK-Ay mice. European Journal of Medicinal Chemistry, 127, 1035–1046. https://doi.org/10.1016/j.ejmech.2016.11.015.

    Article  CAS  PubMed  Google Scholar 

  4. Ouassou, H., Zahidi, T., Bouknana, S., Bouhrim, M., Mekhfi, H., Ziyyat, A., Legssyer, A., Aziz, M., & Bnouham, M. (2018). Inhibition of α-glucosidase, intestinal glucose absorption, and antidiabetic properties by Caralluma europaea. Evidence-based Complementary and Alternative Medicine, 2018, 1–8. https://doi.org/10.1155/2018/9589472.

    Article  Google Scholar 

  5. Amiri, B., Hosseini, N. S., Taktaz, F., Amini, K., Rahmani, M., Amiri, M., Sadrjavadi, K., Jangholi, A., & Esmaeili, S. (2019). Inhibitory effects of selected antibiotics on the activities of α-amylase and α-glucosidase: in-vitro, in-vivo and theoretical studies. European Journal of Pharmaceutical Sciences, 138, 105040. https://doi.org/10.1016/j.ejps.2019.105040.

    Article  CAS  PubMed  Google Scholar 

  6. Esmaeili, S., Azizian, S., Shahmoradi, B., Moradi, S., Shahlaei, M., & Khodarahmi, R. (2019). Dipyridamole inhibits α-amylase/α-glucosidase at sub-micromolar concentrations; in-vitro, in-vivo and theoretical studies. Bioorganic Chemistry, 88, 102972. https://doi.org/10.1016/j.bioorg.2019.102972.

    Article  CAS  PubMed  Google Scholar 

  7. Tomášová, P., Bugáňová, M., Pelantová, H., Holubová, M., Šedivá, B., Železná, B., Haluzík, M., Maletínská, L., Kuneš, J., & Kuzma, M. (2019). Metabolomics based on MS in mice with diet-induced obesity and type 2 diabetes mellitus: the effect of vildagliptin, metformin, and their combination. Applied Biochemistry and Biotechnology, 188(1), 165–184. https://doi.org/10.1007/s12010-018-2899-8.

    Article  CAS  PubMed  Google Scholar 

  8. Fatmawati, S., Shimizu, K., & Kondo, R. (2011). Ganoderol B: a potent α-glucosidase inhibitor isolated from the fruiting body of Ganoderma lucidum. Phytomedicine, 18(12), 1053–1055. https://doi.org/10.1016/j.phymed.2011.03.011.

    Article  CAS  PubMed  Google Scholar 

  9. Peng, X., Zhang, G., Liao, Y., & Gong, D. (2016). Inhibitory kinetics and mechanism of kaempferol on α-glucosidase. Food Chemistry, 190, 207–215. https://doi.org/10.1016/j.foodchem.2015.05.088.

    Article  CAS  PubMed  Google Scholar 

  10. Gou, L., Zhan, Y., Lee, J., Li, X., Lü, Z. R., Zhou, H. M., Lu, H., Wang, X. Y., Park, Y. D., & Yang, J. M. (2015). Effects of L-malic acid on alpha-glucosidase: Inhibition kinetics and computational molecular dynamics simulations. Applied Biochemistry and Biotechnology, 175(4), 2232–2245. https://doi.org/10.1007/s12010-014-1429-6.

    Article  CAS  PubMed  Google Scholar 

  11. Singh, B., Kaur, T., Kaur, S., Manhas, R. K., & Kaur, A. (2015). An alpha-glucosidase inhibitor from an endophytic Cladosporium sp. with potential as a biocontrol agent. Applied Biochemistry and Biotechnology, 175(4), 2020–2034. https://doi.org/10.1007/s12010-014-1325-0.

    Article  CAS  PubMed  Google Scholar 

  12. Majouli, K., Hlila, M. B., Hamdi, A., Flamini, G., Jannet, H. B., & Kenani, A. (2016). Antioxidant activity and α-glicosidase inhibition by essential oils from Hertia cheirifolia (L.). Industrial Crops and Products, 82, 23–28. https://doi.org/10.1016/j.indcrop.2015.12.015.

    Article  CAS  Google Scholar 

  13. Rouzbehan, S., Moein, S., Homaei, A., & Moein, M. R. (2017). Kinetics of a-glicosidase inhibition by different fractions of three species of Labiatae extracts: a new diabetes treatment model. Pharmaceutical Biology, 55(1), 1483–1488. https://doi.org/10.1080/13880209.2017.1306569.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ma, H. T., Hsieh, J. F., & Chen, S. T. (2015). Anti-diabetic effects of Ganoderma lucidum. Phytochemistry, 114, 109–113. https://doi.org/10.1016/j.phytochem.2015.02.017.

    Article  CAS  PubMed  Google Scholar 

  15. Aryaeian, N., Sedehi, S. K., & Arablou, T. (2017). Polyphenols and their effects on diabetes management: a review. Medical Journal of The Islamic Republic of Iran, 31, 134. https://doi.org/10.14196/mjiri.31.134.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Bühler, R. M. M., Müller, B. L., Moritz, D. E., Vendruscolo, F., Oliveira, D., & Ninow, J. L. (2015). Influence of light intensity on growth and pigment production by Monascus ruber in submerged fermentation. Applied Biochemistry and Biotechnology, 176(5), 1277–1289. https://doi.org/10.1007/s12010-015-1645-8.

    Article  CAS  PubMed  Google Scholar 

  17. Tel-Çayan, G., Öztürk, M., Duru, M. E., Rehman, M. U., Adhikari, A., Türkoglu, A., & Choudhary, M. I. (2015). Phytochemical investigation, antioxidant and anticholinesterase activities of Ganoderma adspersum. Industrial Crops and Products, 76, 749–754. https://doi.org/10.1016/j.indcrop.2015.07.042.

    Article  CAS  Google Scholar 

  18. Li, H. J., Zhang, D. H., Yue, T. H., Jiang, L. X., Yu, X., Zhao, P., Li, T., & Xu, J. W. (2016). Improved polysaccharide production in a submerged culture of Ganoderma lucidum by the heterologous expression of Vitreoscilla hemoglobin gene. Journal of Biotechnology, 10, 132–137. https://doi.org/10.1016/j.jbiotec.2015.11.011.

    Article  CAS  Google Scholar 

  19. Klupp, N. L., Kiat, H., Bensoussan, A., Steiner, G. Z., & Chang, D. H. (2016). A double-blind, randomised, placebo-controlled trial of Ganoderma lucidum for the treatment of cardiovascular risk factors of metabolic syndrome. Scientific Reports, 6. https://doi.org/10.1038/srep29540.

  20. Ma, K., Ren, J., Han, J., Bao, L., Li, L., Yao, Y., Sun, C., Zhou, B., Liu, H. (2014) Ganoboninketals A-C, antiplasmodial 3,4-seco-27-norlanostane triterpenes from Ganoderma boninense pat. Journal of Natural Products, 77, 1847–1852. https://doi.org/10.1021/np5002863, 8.

  21. Baby, S., Johnson, A. J., & Govindan, B. (2015). Secondary metabolites from Ganoderma. Phytochemistry, 114, 66–101. https://doi.org/10.1016/j.phytochem.2015.03.010.

    Article  CAS  PubMed  Google Scholar 

  22. Chan, W. K., Lam, D. T., Law, H. K., Wong, W. T., Koo, M. W., Lau, A. S., Lau, Y. L., & Chan, G. C. (2005). Ganoderma lucidum mycelium and spore extracts as natural adjuvants for immunotherapy. The Journal of Alternative and Complementary Medicine, 11, 1047–1057. https://doi.org/10.1089/acm.2005.11.1047.

    Article  PubMed  Google Scholar 

  23. Zárate-Chaves, C. A., Romero-Rodríguez, M. C., Niño-Arias, F. C., Robles-Camargo, J., Linares-Linares, M., Rodríguez-Bocanegra, M. X., & Gutiérrez-Rojas, I. (2013). Optimizing a culture medium for biomass and phenolic compounds production using Ganoderma lucidum. Brazilian Journal of Microbiology, 44(1), 215–223. https://doi.org/10.1590/S1517-83822013005000032.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Mishra, J., Joshi, A., Rajput, R., Singh, K., Bansal, A., & Misra, K. (2018). Phenolic rich fractions from mycelium and fruiting body of Ganoderma lucidum inhibit bacterial pathogens mediated by generation of reactive oxygen species and protein leakage and modulate hypoxic stress in HEK 293 cell line. Advances in Pharmacological Sciences, 17. https://doi.org/10.1155/2018/6285615.

  25. Rubel, R., Santos, L. F., Santa, H. S. D., Vandenberghe, L. P. S., Woiciechowski, A. L., Carvalho, J. C., Habu, S., Vítola, F. M. D., Augur, C., & Soccol, C. R. (2014). Analysis and glycosyl composition of the exopolysaccharide isolated from submerged fermentation of Ganoderma lucidum CG144. Acta Societatis Botanicorum Poloniae, 83, 239–241. https://doi.org/10.5586/asbp.2014.020.

    Article  Google Scholar 

  26. Costa, T. M., Kaufmann, V., Paganelli, C. J., Siebert, D. A., Micke, G. A., Alberton, M. D., Tavares, L. B. B., & De Oliveira, D. (2019). Kinetic identification of phenolic compounds and potential production of caffeic acid by Ganoderma lipsiense in solid-state fermentation. Bioprocess and Biosystems Engineering, 42(8), 1325–1332. https://doi.org/10.1007/s00449-019-02131-8.

    Article  CAS  PubMed  Google Scholar 

  27. Zhipeng, Y., Yongguang, Y., Wenzhu, Z., Yiding, Y., Boqun, L., Jingbo, L., & Feng, C. (2011). Anti-diabetic activity peptides from albumin against α-glucosidase and α-amylase. Food Chemistry, 129, 1376–1382. https://doi.org/10.1016/j.foodchem.2012.06.088.

    Article  CAS  Google Scholar 

  28. Matsui, T., Ebuchi, S., Fujise, T., Abesundara, K. J., Doi, S., Yamada, H., & Matsumoto, K. (2004). Strong antihyperglycemic effects of water-soluble fraction of Brazilian propolis and its bioactive constituent, 3,4,5-tri-O-caffeoylquinic acid. Biological and Pharmaceutical Bulletin, 27(11), 1797–1803. https://doi.org/10.1248/bpb.27.1797.

    Article  CAS  PubMed  Google Scholar 

  29. Vongsak, B., Kongkiatpaiboon, S., Jaisamut, S., Machana, S., & Pattarapanich, C. (2015). In vitro alpha glucosidase inhibition and free-radical scavenging activity of propolis from Thai stingless bees in mangosteen orchard. Revista Brasileira de Farmacognosia, 25, 445–450. https://doi.org/10.1016/j.bjp.2015.07.004.

    Article  CAS  Google Scholar 

  30. Choi, J. H., & Kim, S. (2018). Mechanisms of attenuation of clot formation and acute thromboembolism by syringic acid in mice. Journal of Functional Foods, 43, 112–122. https://doi.org/10.1016/j.jff.2018.02.004.

    Article  CAS  Google Scholar 

  31. Rasouli, H., Hosseini-Ghazvini, S. M. B., Adibi, H., & Khodarahmi, R. (2017). Differential α-amylase/α-glucosidase inhibitory activities of plant-derived phenolic compounds: a virtual screening perspective for the treatment of obesity and diabetes. Food & Function, 8(5), 1942–1954. https://doi.org/10.1039/C7FO00220C.

    Article  CAS  Google Scholar 

  32. Chuyen, N. V., Kurata, T., Kato, H., & Fujimaki, M. (1982). Antimicrobial activity of Kumazasa (Sasa albo-marginata). Agricultural and Biological Chemistry, 46, 971–978. https://doi.org/10.1080/00021369.1982.10865185.

    Article  Google Scholar 

  33. BPDB: BIO-PESTICIDES DATABASE. University of Hertfordshire. Octenol. https://sitem.herts.ac.uk/aeru/bpdb/Reports/2063.htm. (Accessed 09 nov 2018).

  34. Shah, T. Z., Ali, A. B., Jafri, S. A., & Qazi, M. H. (2013). Effect of nicotinic acid (vitamin B3 or niacin) on the lipid profile of diabetic and non–diabetic rats. Pakistan Journal of Medical Science, 29, 1259–1264.

    Google Scholar 

  35. Awla, H. K., Kadir, J., Othman, R., Rashid, T. S., & Wong, M. Y. (2016). Bioactive compounds produced by Streptomyces sp. isolate UPMRS4 and antifungal activity against Pyricularia oryzae. American Journal of Plant Sciences, 7, 1077–1085. https://doi.org/10.4236/ajps.2016.77103.

    Article  CAS  Google Scholar 

  36. Ser, H. L., Palanisamy, U. D., Yin, W. F., Malek, S. N. A., Chan, K. G., & Goh, B. H. (2015). Presence of antioxidative agent, pyrrolo[1,2-a]pyrazine-1,4-dione, hexahydro- in newly isolated Streptomyces mangrovisoli sp. nov. Frontiers in Microbiology, 6. https://doi.org/10.3389/fmicb.2015.00854.

  37. Spanova, M., & Daum, G. (2011). Squalene—biochemistry, molecular biology, process biotechnology, and applications. European Journal of Lipid Science and Technology, 113, 1299–1320. https://doi.org/10.1002/ejlt.201100203.

    Article  CAS  Google Scholar 

  38. Chen, J., Lu, W., Chen, H., Bian, X., & Yang, G. (2019). A new series of salicylic acid derivatives as non-saccharide α-glucosidase inhibitors and antioxidants. Biological and Pharmaceutical Bulletin, 42, 231–246. https://doi.org/10.1248/bpb.b18-00661.

    Article  CAS  PubMed  Google Scholar 

  39. Kang, M. G., Yi, S. H., & Lee, J. S. (2013). Production and characterization of a new α-glucosidase inhibitory peptide from Aspergillus oryzae N159-1. Mycobiology, 41(3), 149–154. https://doi.org/10.5941/MYCO.2013.41.3.149.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Jing, L., Zong, S., Li, J., Surhio, M. M., & Ye, M. (2016). Purification, structural features and inhibition activity on α-glicosidase of a novel polysaccharide from Lachnum YM406. Process Biochemistry, 51, 1706–1713. https://doi.org/10.1016/j.procbio.2016.08.007.

    Article  CAS  Google Scholar 

  41. Artanti, N., Tachibana, S., Kardono, L. B. S., & Sukiman, H. (2012). Isolation of α-glicosidase inhibitors produced by an endophytic fungus, Colletotrichum sp. TSC13 from Taxus sumatrana. Pakistan Journal of Medical Science, 15, 673–679. https://doi.org/10.3923/pjbs.2012.673.679.

    Article  Google Scholar 

  42. Su, C. H., Hsu, C. H., & Ng, L. T. (2013). Inhibitory potential of fatty acids on key enzymes related to type 2 diabetes. BioFactors, 39(4), 415–421. https://doi.org/10.1002/biof.1082.

    Article  CAS  PubMed  Google Scholar 

  43. Nguyen, T. H., & Kim, S. M. (2015). α-Glicosidase inhibitory activities of fatty acids purified from the internal organ of sea cucumber Stichopus japonicas. Journal of Food Science, 80, 841–847. https://doi.org/10.1111/1750-3841.12810.

    Article  CAS  Google Scholar 

  44. Sonam, K. S., & Guleria, S. (2017). Synergistic antioxidant activity of natural products. Annals of Pharmacology and Pharmaceutics, 2, 1–6.

    Google Scholar 

  45. Kim, S. D., & Nho, H. J. (2004). Isolation and characterization of alpha-glucosidase inhibitor from the fungus Ganoderma lucidum. Journal of Microbiology, 42, 223–227.

    CAS  Google Scholar 

  46. Dougall, I.G., Unitt, J. (2015) Evaluation of the biological activity of compounds: techniques and mechanism of action studies. Chapter 2; the practice of medicinal chemistry (fourth edition). Pages 15-43. https://doi.org/10.1016/B978-0-12-417205-0.00002-X.

  47. Eun, H.M. (1996) Enzymes and nucleic acids. Enzymology primer for recombinant DNA technology, chapter 1. Elsevier inc. all, 1996. https://doi.org/10.1016/B978-0-12-243740-3.X5000-5.

  48. Kumar, S., Narwal, S., Kumar, V., & Prakash, O. (2011). α-Glucosidase inhibitors from plants: a natural approach to treat diabetes. Pharmacognosy Reviews, 5, 19–29. https://doi.org/10.4103/0973-7847.79096.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors are grateful to the Coordination for the Improvement of Higher Education Personnel - (CAPES) Brazil - for the financial support (Code 001). Authors D. Oliveira and L.B.B. Tavares are fellowship holders of the National Council for Scientific and Technological Development (CNPq).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Débora de Oliveira.

Additional information

Publisher’s Note

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

Electronic Supplementary Material

ESM 1

(DOCX 177 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Costa, T.M., Mayer, D.A., Siebert, D.A. et al. Kinetics Analysis of the Inhibitory Effects of Alpha-Glucosidase and Identification of Compounds from Ganoderma lipsiense Mycelium. Appl Biochem Biotechnol 191, 996–1009 (2020). https://doi.org/10.1007/s12010-020-03239-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-020-03239-4

Keywords

Navigation