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. 2022 Mar 1:16:571-586.
doi: 10.2147/DDDT.S351100. eCollection 2022.

Alleviating Aspirin-Induced Gastric Injury by Binding Aspirin to β-Lactoglobulin

Jin Chen #  1 , Min Gong #  1 , Zhuo Huang  1 , Fang Wang  2 , Yajing Wang  3 , Zuquan Hu  1 , Zhu Zeng  1 , Yun Wang  2
Affiliations

Alleviating Aspirin-Induced Gastric Injury by Binding Aspirin to β-Lactoglobulin

Jin Chen et al. Drug Des Devel Ther. .

Abstract

Purpose: Gastric injury is a major issue for long-term administration of aspirin. In this work, we tried to explore the possibility of using BLG to alleviate aspirin-induced gastric injury, because of excellent abilities of BLG in loading drug molecules.

Methods: Various spectroscopic techniques and molecular docking methods were applied to investigate the interaction mechanism between BLG and aspirin. Animal experiments were performed to figure out the effects of taking aspirin-BLG on the stomach.

Results: Our results demonstrate that aspirin could bind with BLG to form stable aspirin-BLG complex (the binding constant Kb = 2.051 × 103 M-1). The formation process is endothermic (∆H>0) and the main acting force is hydrophobic force. Our data also show that the aspirin-BLG complex is formed with a higher affinity in simulated gastric fluid and could remain stable for several hours, which might arise from its special binding mode under acidic condition and the resistance of BLG to gastric digestion. Furthermore, animal models (rats with aspirin-induced gastric damage) were built. The results of animal experiments reveal that the oral administration of aspirin-BLG could cause less damage to gastric tissue, and it also hardly triggers obvious inflammatory responses.

Conclusion: This study would contribute to an in-depth understanding of the interaction mechanism between BLG and aspirin. It is reasonable to believe that using BLG to bind with aspirin would be a potential way to alleviate the aspirin-induced gastric injury.

Keywords: aspirin; beta-lactoglobulin; gastric injury; molecular docking; static quenching.

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Conflict of interest statement

The authors have no conflicts of interest for this work to declare.

Figures

None
Graphical abstract
Figure 1
Figure 1
(A) Fluorescence emission spectra of BLG (5 μM) in presence of different concentrations of aspirin (A = 0, B = 200, C = 600, D = 1000, E = 1200, F = 1400, G = 1600, H = 1800, and I = 2000 μM). (B) Modified Stern-Volmer plots of BLG (5 μM) interaction with different concentrations of aspirin. (C) Overlaps of the fluorescence emission spectra of BLG (5 μM) and the UV-vis absorbance spectra of aspirin (1000 μM). (D) Circular dichroism spectra of BLG (5 μM) in the absence and presence of aspirin at 37 °C. (E) ANS emission of BLG (5 μM) upon increasing concentrations of aspirin (A = 0, B = 400, C = 800, D = 1200, E = 1600 and F = 2000 μM) at 37 °C; the inset is the wavelength values of emission maxima. All solutions were prepared with PBS solution at pH=7.4.
Figure 2
Figure 2
(A) The curves of log [(F0-F)/F] vs log[C] of BLG interaction with aspirin at pH 7.4. (B) Molecular docking analysis of aspirin-BLG complex at pH 7.4.
Figure 3
Figure 3
(A) The F/F0 values of BLG (5 μM) interaction with different concentrations of aspirin in PBS solution and simulated gastric fluid at 37 °C for 40 min. (B) The F/F0 values of BLG (10 μM) interaction with aspirin (0, 800, 1200 and 1600 μM) in simulated gastric fluid at 37 °C for different times.
Figure 4
Figure 4
(A) Molecular docking analysis of aspirin-BLG complex at pH 2.0. (B) Representative SDS-PAGE patterns of samples obtained by digesting BLG in simulated gastric fluid for different times. (C) The gray values obtained from the SDS-PAGE patterns.
Figure 5
Figure 5
Representative morphological photographs of gastric tissues from the rats of different groups: (A) PBS group; (B) aspirin group, arrows indicate hemorrhagic streaks on the mucosal surface; (C) aspirin-BLG group. Representative hematoxylin-eosin staining images of gastric tissues from the rats of different groups: (D) PBS group; (E) aspirin group, arrows indicate disruption and erosion of gastric mucosa; (F) aspirin-BLG group, arrows indicate slightly shredded mucosal surface epithelium.
Figure 6
Figure 6
qRT-PCR analysis for the genes expression levels of pro-inflammatory cytokines in gastric tissues: (A) TNF-α; (B) IL-1β.
See this image and copyright information in PMC

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