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Effect of ellagitannin metabolites ellagic acid and urolithins A-D on the non-enzymatic glycation of human serum albumin and inhibiting mechanisms

Chunyan Penga, Wenna Zhoua, Xing Xiea,b(), Feiyan Lua, Linju Xua, Qinghui Wena, Zongcai Tua,c, Lu Zhanga()
National R&D Center of Freshwater Fish Processing, College of Life Science, Jiangxi Normal University, Nanchang 330022, China
College of Health, Jiangxi Normal University, Nanchang 330022, China
State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China

Peer review under responsibility of Beijing Academy of Food Sciences.

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Abstract

Effect of ellagitannins gut microbiota metabolites ellagic acid (EA) and urolithin A-urolithin D (UroA-UroD) on human serum albumin (HSA) glycation were firstly evaluated in this research. The inhibition mechanisms were investigated by methylglyoxal (MGO) trapping and radical scavenging ability assays, docking studies and nano LC-orbitrap-MS/MS technology. Results indicated that the inhibition of urolithins on HSA glycation was highly positive correlated with the number of phenolic hydroxy groups. Addition of UroD and EA could effectively enhance the content of free amino group, suppress dicarbonyl compounds and advanced glycation end-products (AGEs) formation, alleviated tryptophan and protein oxidation, inhibited HSA amyloid-like aggregation. They could also trap MGO and scavenge 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH·) and 2,2’-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid free radical (ABTS+·). Molecular docking indicated that EA and UroA-UroD interact with HSA mainly through hydrogen bound and hydrophobic interaction, among which 2 or 3 hydrogen bonds were formed. The number of glycation sites were reduced from 11 to 10, 10, 7, and 10, respectively, when 90 μmol/L of EA, UroA, UroC and UroD were added. However, weak inhibition was observed on UroA and UroB. These findings can provide scientific evidence for the application of ellagitannins-rich foods in alleviating diabetic complications.

Keywords

Ellagitannin metabolitesHuman serum albuminNon-enzymatic glycation

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Food Science and Human Wellness
Volume 14 Issue 5,
May 2025
Article number: 9250107
DOI: 10.26599/FSHW.2024.9250107
Cite this article:
Peng C, Zhou W, Xie X, et al. Effect of ellagitannin metabolites ellagic acid and urolithins A-D on the non-enzymatic glycation of human serum albumin and inhibiting mechanisms. Food Science and Human Wellness, 2025, 14(5): 9250107. https://doi.org/10.26599/FSHW.2024.9250107
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Glycation peptides and glycation sites identified in G-HSA with and without EA, UroA, UroB, UroC, and UroD.

No.Native peptidePeptide locationGlycated peptideSequence*Glycated site
Note: * Red K indicates the glycated sites.
G-HSA without compound
1499.98734+123−138540.50044+NECFLQHKDDNPNLPRLys130
2554.91233+185−198608.92943+YKAAFTECCQAADKLys186
3387.45384+299−310468.47994+LKECCEKPLLEKLys300; Lys305
4653.31162+301−310734.33792+ECCEKPLLEKLys305
5399.85613+338−347453.87373+DVCKNYAEAKLys341
6489.57373+497−508543.59123+VTKCCTESLVNRLys499
7430.92123+549−558484.93843+KQTALVELVKLys549; Lys558
8500.54803+585−597554.56523+ADDKETCFAEEGKLys588
9543.24623+585−598597.26353+ADDKETCFAEEGKKLys588
10407.68604+585−598488.71224+ADDKETCFAEEGKKLys588; Lys597
11400.18443+589−598454.20183+ETCFAEEGKKLys597
12571.34972+598−609652.37632+KLVAASQAALGLLys598
G-HSA with EA
1409.53903+35−44463.55673+FKDLGEENFKLys36
2666.31453+123−138720.33143+NECFLQHKDDNPNLPRLys130
3879.41133+118−138933.43023+QEPERNECFLQHKDDNPNLPRLys130
4559.67555+139−161592.08655+LVRPEVDVMCTAFHDNEETFLKKLys161
5516.26983+299−310570.28703+LKECCEKPLLEKLys300
6399.85633+338−347453.87403+DVCKNYAEAKLys341
7547.31673+438−452601.33413+KVPQVSTPTLVEVSRLys438
8376.90323+549−558484.93843+KQTALVELVKLys549; Lys558
9500.54783+585−597554.56513+ADDKETCFAEEGKLys588
10400.18423+589−598454.20183+ETCFAEEGKKLys597
11407.68614+585−598488.71254+ADDKETCFAEEGKKLys588; Lys597
G-HSA with UroA
1528.05025+118−138560.46085+QEPERNECFLQHKDDNPNLPRLys130
2352.53333+161−168406.55113+KYLYEIARLys161
3554.91223+185−198608.92983+YKAAFTECCQAADKLys186
4708.99963+187−205763.01753+AAFTECCQAADKAACLLPKLys198
5435.87633+301−310489.89373+ECCEKPLLEKLys305
6489.57333+497−508543.59113+VTKCCTESLVNRLys499
7376.90313+549−558430.92083+KQTALVELVKLys549
8500.54733+585−597554.56503+ADDKETCFAEEGKLys588
9543.24613+585−598651.28113+ADDKETCFAEEGKKLys588; Lys597
10571.35002+598−609652.37652+KLVAASQAALGLLys598
G-HSA with UroB
1666.31413+123−138720.33063+NECFLQHKDDNPNLPRLys130
2554.91263+185−198608.92973+YKAAFTECCQAADKLys186
3380.44854+206−219420.96154+LDELRDEGKASSAKLys214
4418.22273+247−257472.24013+FPKAEFAEVSKLys249
5550.96903+250−264604.98683+AEFAEVSKLVTDLTKLys257
6387.45354+299−310427.96654+LKECCEKPLLEKLys300
7547.31653+438−452601.33443+KVPQVSTPTLVEVSRLys438
8376.90323+549−558484.93873+KQTALVELVKLys549; Lys558
9500.54723+585−597554.56453+ADDKETCFAEEGKLys588
10407.68624+585−598488.71274+ADDKETCFAEEGKKLys588; Lys597
G-HSA with UroC
1666.31343+123−138720.33113+NECFLQHKDDNPNLPRLys130
2506.92883+206−219560.94663+LDELRDEGKASSAKLys214
3516.26893+299−310570.28633+LKECCEKPLLEKLys300
4376.90333+549−558484.93823+KQTALVELVKLys549; Lys558
5614.30853+566−581668.32603+EQLKAVMDDFAAFVEKLys569
6407.68574+585−598448.19884+ADDKETCFAEEGKKLys588
7500.54803+585−597554.56533+ADDKETCFAEEGKLys588
G-HSA with UroD
1409.53883+35−44463.55653+FKDLGEENFKLys36
2683.12425+76−105715.53485+TCVADESAENCDKSLHTLFGDKLCTVATLRLys88
3666.31313+123−138720.33073+NECFLQHKDDNPNLPRLys130
4559.67495+139−161592.08535+LVRPEVDVMCTAFHDNEETFLKKLys160
5609.99223+199−214664.00853+AACLLPKLDELRDEGKLys205
6825.94962+250−264906.97582+AEFAEVSKLVTDLTKLys257
7435.87593+301−310489.89343+ECCEKPLLEKLys305
8599.28082+338−347680.30712+DVCKNYAEAKLys341
9376.90323+549−558430.92083+KQTALVELVKLys549
10500.54713+585−597554.56453+ADDKETCFAEEGKLys588