Mushroom-Derived Compounds as Inhibitors of Advanced Glycation End-Products
Source abstract
Abstract
Mushrooms like Inonotus obliquus and Ganoderma lucidum show significant pharmacological promise. This review analyzes fungi as sources of natural inhibitors against Advanced Glycation End-products (AGEs)—key drivers of diabetes and neurodegeneration. We highlight that extracts from Lignosus rhinocerus and Auricularia auricula exhibit antiglycation potency (IC50 as low as 0.001 mg/mL) superior to aminoguanidine. Inhibitory effects are attributed to bioactive fractions including FYGL proteoglycans, uronic acid-rich polysaccharides, and fungal-specific metabolites like ergothioneine. These compounds act through multi-target mechanisms across the glycation cascade: competitive inhibition of Schiff base formation, trapping reactive dicarbonyls (e.g., methylglyoxal), transition metal chelation, and direct scavenging of reactive oxygen species (ROS). Furthermore, the review addresses the transition from in vitro potency to in vivo efficacy (RAGE pathway modulation), stability during food processing (UV-B irradiation), and critical safety issues regarding heavy metal bioaccumulation. Mushroom-derived inhibitors represent a sustainable therapeutic alternative to synthetic agents, offering broader protection against glycative stress. This synthesis provides a foundation for developing standardized mushroom-based nutraceuticals for managing AGE-related chronic disorders.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Advanced Glycation End Products research · Fungal Biology and Applications · Antioxidants, Aging, Portulaca oleracea
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Chemistry and Biochemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia
References (57)
Show source-provided references
1. Nutritional and medicinal importance of mushrooms10.5897/JMPR09.565 ↗
2. Inonotus obliquus—From folk medicine to clinical use10.1016/j.jtcme.2020.08.003 ↗
3. Fomitopsis officinalis mushroom ancient gold mine of functional components and biological activities for modern medicine10.4103/epj.epj_46_19 ↗
4. Medicinal potential of mycelium and fruiting bodies of an arboreal mushroom Fomitopsis officinalis in therapy of lifestyle diseases10.1038/s41598-020-76899-1 ↗
5. Ethnomycological use of Fomes fomentarius (L.) Fr. and Piptoporus betulinus (Bull.) P. Karst. in Transylvania, Romania10.1007/s10722-015-0335-2 ↗
6. Rašeta, M., Kebert, M., Pintać Šarac, D., Mišković, J., Berežni, S., Kulmány, Á.E., Zupkó, I., Karaman, M., and Jovanović-Šanta, S. (2025). Bioactive Potential of Balkan Fomes fomentarius Strains: Novel Insights into Comparative Mycochemical Composition and Antioxidant, Anti-Acetylcholinesterase, and Antiproliferative Activities. Microorganisms, 13.10.20944/preprints202504.0505.v1 ↗
7. European medicinal polypores—A modern view on traditional uses10.1016/j.jep.2014.04.030 ↗
8. Phase I/II study of a Ganoderma lucidum extract (Ganopofy) in patients with advanced cancer
9. Antibacterial and antiviral value of the genus Ganoderma P. Karst. species (Aphyllophoromycetideae): A review10.1615/InterJMedicMush.v5.i3.20 ↗
10. A Phase I/II study of Ling Zhi mushroom Ganoderma lucidum (W.Curt.:Fr.) Lloyd (Aphyllophoromycetideae) extract in patients with type II diabetes mellitus
11. Medicinal value of species of the family Agaricaceae cohn (higher Basidiomycetes) current stage of knowledge and future perspectives
12. Immunomodulatory activities of mushroom glucans and polysaccharide–protein complexes in animals and humans (a review)
13. Medicinal mushroom science: History, current status, future trends, and unsolved problems10.1615/IntJMedMushr.v12.i1.10 ↗
14. Cheung, P.C.K. (2008). Regulatory issues of mushrooms as functional foods and dietary supplements: Safety and efficacy. Mushrooms as Functional Foods, Wiley.10.1002/9780470367285 ↗
15. An overview on glycation: Molecular mechanisms, impact on proteins, pathogenesis, and inhibition10.1007/s12551-024-01188-4 ↗
16. Natural Products as a Source of Inspiration for Novel Inhibitors of Advanced Glycation Endproducts (AGEs) Formation10.1055/a-1527-7611 ↗
17. Naturally occurring inhibitors against the formation of advanced glycation end-products10.1039/c1fo10034c ↗
18. Reddy, V.P., Aryal, P., and Darkwah, E.K. (2022). Advanced Glycation End Products in Health and Disease. Microorganisms, 10.10.3390/microorganisms10091848 ↗
19. Importance of measuring products of non-enzymatic glycation of proteins10.1016/j.clinbiochem.2004.09.007 ↗
20. Twarda-Clapa, A., Olczak, A., Białkowska, A.M., and Koziołkiewicz, M. (2022). Advanced Glycation End-Products (AGEs): Formation, Chemistry, Classification, Receptors, and Diseases Related to AGEs. Cells, 11.10.3390/cells11081312 ↗
21. Advanced Glycation End Products (AGEs): Biochemistry, Signaling, Analytical Methods, and Epigenetic Effects
22. Chen, N., Wang, N., Fang, Q., Yu, Z., Hu, Y., Jin, J., and Yang, S. (2025). Inhibition effect of AGEs formation in vitro by the two novel peptides EDYGA and DLLCIC derived from Pelodiscus sinensis. Front. Nutr., 12.10.3389/fnut.2025.1537338 ↗
23. Recent development of plant products with anti-glycation activity: A review10.1039/C4RA14211J ↗
24. Effects of quercetin and l-ascorbic acid on heterocyclic amines and advanced glycation end products production in roasted eel and lipid-mediated inhibition mechanism analysis10.1016/j.foodchem.2024.138394 ↗
25. Novel advances in inhibiting advanced glycation end product formation using natural compounds10.1016/j.biopha.2021.111750 ↗
26. Mota, K.O., de Vasconcelos, C.M.L., Kirshenbaum, L.A., and Dhalla, N.S. (2025). The Role of Advanced Glycation End-Products in the Pathophysiology and Pharmacotherapy of Cardiovascular Disease. Int. J. Mol. Sci., 26.10.3390/ijms26157311 ↗
27. Evaluation in vitro of AGE-crosslinks breaking ability of rosmarinic acid
28. Resveratrol Inhibits AGEs-Induced Proliferation and Collagen Synthesis Activity in Vascular Smooth Muscle Cells from Stroke-Prone Spontaneously Hypertensive Rats10.1006/bbrc.2000.3097 ↗
29. Curcumin eliminates the effect of advanced glycation end-products (AGEs) on the divergent regulation of gene expression of receptors of AGEs by interrupting leptin signaling10.1038/labinvest.2014.42 ↗
30. Understanding the mechanism of non-enzymatic glycation inhibition by cinnamic acid: An in vitro interaction and molecular modelling study10.1039/C6RA12321J ↗
31. Inhibition of Advanced Glycation End Product Formation in Rat Tail Tendons by Polydatin and p-Coumaric acid: An In Vitro Study10.1007/s12010-021-03762-y ↗
32. Inhibitory effect of quercetin in the formation of advance glycation end products of human serum albumin: An in vitro and molecular interaction study10.1016/j.ijbiomac.2015.05.004 ↗
33. Effect of rosmarinic acid and carnosic acid on AGEs formation in vitro10.1016/j.foodchem.2016.11.056 ↗
34. Comparison of Protective Effects of Phenolic Acids on Protein Glycation of BSA Supported by In Vitro and Docking Studies10.1155/2023/9984618 ↗
35. Chugh, R.M., Mittal, P., Mp, N., Arora, T., Bhattacharya, T., Chopra, H., Cavalu, S., and Gautam, R.K. (2022). Fungal Mushrooms: A Natural Compound with Therapeutic Applications. Front. Pharmacol., 13.10.3389/fphar.2022.925387 ↗
36. Bhambri, A., Srivastava, M., Mahale, V.G., Mahale, S., and Karn, S.K. (2022). Mushrooms as Potential Sources of Active Metabolites and Medicines. Front. Microbiol., 13.10.3389/fmicb.2022.837266 ↗
37. Synergistic anti-glycation and antioxidant interaction among different mushroom extract combinations
38. Yap, H.Y., Tan, N.H., Ng, S.T., Tan, C.S., and Fung, S.Y. (2018). Inhibition of Protein Glycation by Tiger Milk Mushroom [Lignosus rhinocerus (Cooke) Ryvarden] and Search for Potential Anti-diabetic Activity-Related Metabolic Pathways by Genomic and Transcriptomic Data Mining. Front. Pharmacol., 9.10.3389/fphar.2018.00103 ↗
39. Anti-glycated and antiradical activities in vitro of polysaccharides from Ganoderma capense10.4103/0973-1296.108132 ↗
40. Zhang, Y., Pan, Y., Li, J., Zhang, Z., He, Y., Yang, H., and Zhou, P. (2022). Inhibition on α-Glucosidase Activity and Non-Enzymatic Glycation by an Anti-Oxidative Proteoglycan from Ganoderma lucidum. Molecules, 27.10.3390/molecules27051457 ↗
41. Potential inhibitory effect of Auricularia auricula polysaccharide on advanced glycation end-products (AGEs)10.1016/j.ijbiomac.2024.129856 ↗
42. Hypoglycemic Effect of the Degraded Polysaccharides from the Wood Ear Medicinal Mushroom Auricularia auricula-judae (Agaricomycetes)10.1615/IntJMedMushrooms.2019032353 ↗
43. Inhibitory Effect of Bioassay-Guided Fractionation of Mushroom (Pleurotus ostreatus) Extract on Fructose-induced Glycated Hemoglobin and Aggregation in vitro10.5530/pres.15.4.082 ↗
44. Anti-glycation and antioxidant effects of Chaga mushroom decoction extracted with a fermentation medium10.3136/fstr.FSTR-D-22-00120 ↗
45. Fordjour, E., Manful, C.F., Javed, R., Galagedara, L.W., Cuss, C.W., Cheema, M., and Thomas, R. (2023). Chaga mushroom: A super-fungus with countless facets and untapped potential. Front. Pharmacol., 14.10.3389/fphar.2023.1273786 ↗
46. Lin, H., Lin, T.-Y., Lin, J.-A., Cheng, K.-C., Santoso, S.P., Chou, C.-H., and Hsieh, C.-W. (2021). Effect of Pholiota nameko Polysaccharides Inhibiting Methylglyoxal-Induced Glycation Damage In Vitro. Antioxidants, 10.10.3390/antiox10101589 ↗
47. Jovanović, J.A., Mihailović, M., Uskoković, A.S., Grdović, N., Dinić, S., Poznanović, G., Mujić, I., and Vidaković, M. (2017). Evaluation of the Antioxidant and Antiglycation Effects of Lactarius deterrimus and Castanea sativa Extracts on Hepatorenal Injury in Streptozotocin-Induced Diabetic Rats. Front. Pharmacol., 8.10.3389/fphar.2017.00793 ↗
48. Protein glycation inhibitors from the fruiting body of Phellinus linteus10.1248/bpb.31.1968 ↗
49. Chen, W., Tan, H., Liu, Q., Zheng, X., Zhang, H., Liu, Y., and Xu, L. (2019). A Review: The Bioactivities and Pharmacological Applications of Phellinus linteus. Molecules, 24.10.3390/molecules24101888 ↗
50. Pelletier, P., and Pageon, H. (2002). Use of Ergothioneine and/or Its Derivatives as an Anti-Glycation Agent. (0,042,438A1), U.S. Patent, Available online: https://patents.google.com/patent/US20020042438A1/en.
51. Preparation, characterization and antiglycation activities of the novel polysaccharides from Boletus snicus10.1016/j.ijbiomac.2016.07.014 ↗
52. Gallotti, F., and Lavelli, V. (2020). The Effect of UV Irradiation on Vitamin D2 Content and Antioxidant and Antiglycation Activities of Mushrooms. Foods, 9.10.3390/foods9081087 ↗
53. Prooxidant Activity of Polyphenols, Flavonoids, Anthocyanins and Carotenoids: Updated Review of Mechanisms and Catalyzing Metals10.1002/ptr.5643 ↗
54. Are polyphenols antioxidants or pro-oxidants? What do we learn from cell culture and in vivo studies?10.1016/j.abb.2008.01.028 ↗
55. Liuzzi, G.M., Petraglia, T., Latronico, T., Crescenzi, A., and Rossano, R. (2023). Antioxidant Compounds from Edible Mushrooms as Potential Candidates for Treating Age-Related Neurodegenerative Diseases. Nutrients, 15.10.3390/nu15081913 ↗
56. Food and human health applications of edible mushroom by-products10.1016/j.nbt.2024.03.003 ↗
57. Li, Y., Li, H., Yan, J., Wang, Z., Liu, J., Meng, J., Oz, F., Chen, J., Zeng, M., and Feng, C. (Food Front., 2025). Comparative Analysis of Intermediate and Advanced Maillard Reaction Products in Three Types of Commercial Edible Mushroom Products, Food Front., early view.10.1002/fft2.70183 ↗