Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Oct 18;27(20):6995.
doi: 10.3390/molecules27206995.

Inhibitory Effects of Myriocin on Non-Enzymatic Glycation of Bovine Serum Albumin

Libo He  1 , Yang Liu  2 , Junling Xu  1 , Jingjing Li  1 , Guohua Cheng  1 , Jiaxiu Cai  1 , Jinye Dang  1 , Meng Yu  1 , Weiyan Wang  1 , Wei Duan  3 , Ke Liu  1
Affiliations

Inhibitory Effects of Myriocin on Non-Enzymatic Glycation of Bovine Serum Albumin

Libo He et al. Molecules. .

Abstract

Advanced glycation end products (AGEs) are the compounds produced by non-enzymatic glycation of proteins, which are involved in diabetic-related complications. To investigate the potential anti-glycation activity of Myriocin (Myr), a fungal metabolite of Cordyceps, the effect of Myr on the formation of AGEs resulted from the glycation of bovine serum albumin (BSA) and the interaction between Myr and BSA were studied by multiple spectroscopic techniques and computational simulations. We found that Myr inhibited the formation of AGEs at the end stage of glycation reaction and exhibited strong anti-fibrillation activity. Spectroscopic analysis revealed that Myr quenched the fluorescence of BSA in a static process, with the possible formation of a complex (approximate molar ratio of 1:1). The binding between BSA and Myr mainly depended on van der Waals interaction, hydrophobic interactions and hydrogen bond. The synchronous fluorescence and UV-visible (UV-vis) spectra results indicated that the conformation of BSA altered in the presence of Myr. The fluorescent probe displacement experiments and molecular docking suggested that Myr primarily bound to binding site 1 (subdomain IIA) of BSA. These findings demonstrate that Myr is a potential anti-glycation agent and provide a theoretical basis for the further functional research of Myr in the prevention and treatment of AGEs-related diseases.

Keywords: BSA; Myriocin; computational simulations; non-enzymatic glycation; spectroscopic techniques.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Effects of Myr on the glycation products formed in BSA-Glucose model at different stages. (A) Diagram of formation process of advanced glycation end products (AGEs). (B) Content of fructosamine generated at the early stage in BSA-glucose system incubated with Myriocin (Myr) or aminoguanidine (AG), measured by UV absorbance at 530 nm. (C) Inhibition rate of total AGEs generated at the end stage, measured by fluorescence emission at 440 nm with excitation at 350 nm. (D–G) Inhibition rates of different fluorescent AGEs including vesperlysine, crossline, argpyrimidine and pentosidine, measured by fluorescence at λex/λem of 350/405, 380/440, 320/380 and 335/385 nm, respectively. Data were expressed as mean ± SD (n = 3). ns > 0.05, * p < 0.05 and ** p < 0.01 compared with AG.
Figure 2
Figure 2
Effects of Myr on glycation-induced protein amyloid aggregation. (A) ThT fluorescence spectrometry analysis of amyloid-like fibrils in the presence and absence of Myr or AG (aminoguanidine, positive control). (B) The fluorescence microscopy analysis of amyloid-like fibrils in the absence and presence of Myr. *** p < 0.001 compared with native BSA. ### p < 0.001 compared with glycated BSA.
Figure 3
Figure 3
Effects of Myr on glycoxidation fluorescence products. Inhibition rates of formation of dityrosine (A), kynurenine (B) and N′-formyl-kynurenine (C), respectively, measured by fluorescence at 415, 480, and 434 nm with excitation at 330, 365, and 325 nm, respectively. Data were expressed as mean ± SD (n = 3). ns > 0.05, * p < 0.05, ** p < 0.01 and *** p < 0.001 compared with AG.
Figure 4
Figure 4
Fluorescence emission spectra of Myr-BSA system in 10 mM PBS (pH = 7.4) at 293 K. (A) Fluorescence emission spectra for BSA (2 μM) with Myr (0, 2, 4, 6, 8, 10 μM). (B) The fluorescence intensity of BSA at 340 nm in absence and presence of Myr (0–10 μM). (C) The Stern-Volmer plots of fluorescence quenching constant (Kq) for the Myr-BSA complexes at different temperatures. (D) The double logarithmic plots at different temperatures.
Figure 5
Figure 5
Effects of Myr on the conformation of BSA. (A,B) represent the synchronous fluorescence spectra of the interaction between Myr and BSA at Δλ = 15 nm and Δλ = 60 nm, respectively. (C) UV-vis absorption spectra of BSA in absence and presence of Myr (0, 2, 4, 6, 8, 10 μM).
Figure 6
Figure 6
The binding model between BSA and Myr. (A) Fluorescence intensity of BSA-Myr in presence of Met, War and Ibu; pH = 7.0, T = 298K, λex = 280 nm. (B) Binding constant plots of BSA-Myr in presence of Met, War and Ibu; λex = 280 nm. (C) The lowest binding free energy pose for Myr into the BSA site I: 3D view cartoon presentation (left) and the 2D schematic view of the binding interaction (right).
Figure 7
Figure 7
The results of 30 ns MD simulations. (A–C) represent the RMSD, Rg and RMSF values of the BSA and BSA-Myr systems, respectively. (D) Hydrogen bonds involved during the interaction between Myr and binding pocket residues of BSA.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Twarda-Clapa A., Olczak A., Białkowska A.M., Koziołkiewicz M. Advanced Glycation End-Products (AGEs): Formation, Chemistry, Classification, Receptors, and Diseases Related to AGEs. Cells. 2022;11:1312. doi: 10.3390/cells11081312. - DOI - PMC - PubMed
    1. Shen C.-Y., Lu C.-H., Wu C.-H., Li K.-J., Kuo Y.-M., Hsieh S.-C., Yu C.-L. The Development of Maillard Reaction, and Advanced Glycation End Product (AGE)-Receptor for AGE (RAGE) Signaling Inhibitors as Novel Therapeutic Strategies for Patients with AGE-Related Diseases. Molecules. 2020;25:5591. doi: 10.3390/molecules25235591. - DOI - PMC - PubMed
    1. Peppa M., Uribarri J., Vlassara H. Glucose, Advanced Glycation End Products, and Diabetes Complications: What Is New and What Works. Clin. Diabetes. 2003;21:186–187. doi: 10.2337/diaclin.21.4.186. - DOI
    1. Singh V.P., Bali A., Singh N., Jaggi A.S. Advanced Glycation End Products and Diabetic Complications. Korean J. Physiol. Pharmacol. 2014;18:1–14. doi: 10.4196/kjpp.2014.18.1.1. - DOI - PMC - PubMed
    1. Lv X., Lv G.-H., Dai G.-Y., Sun H.-M., Xu H.-Q. Food-advanced glycation end products aggravate the diabetic vascular complications via modulating the AGEs/RAGE pathway. Chin. J. Nat. Med. 2016;14:844–855. doi: 10.1016/S1875-5364(16)30101-7. - DOI - PubMed

LinkOut - more resources