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. 2022 Dec 5;11(12):2406.
doi: 10.3390/antiox11122406.

The Alleviation of Dextran Sulfate Sodium (DSS)-Induced Colitis Correlate with the log P Values of Food-Derived Electrophilic Compounds

Xiang-Rong Cheng  1   2 , Bu-Tao Yu  1   2 , Jie Song  1   2 , Jia-Hui Ma  1   2 , Yu-Yao Chen  1   2 , Chen-Xi Zhang  1   2 , Piao-Han Tu  1   2 , Mitchell N Muskat  3 , Ze-Gang Zhu  4
Affiliations

The Alleviation of Dextran Sulfate Sodium (DSS)-Induced Colitis Correlate with the log P Values of Food-Derived Electrophilic Compounds

Xiang-Rong Cheng et al. Antioxidants (Basel). .

Abstract

Food-derived electrophilic compounds (FECs) are small molecules with electrophilic groups with potential cytoprotective effects. This study investigated the differential effects of six prevalent FECs on colitis in dextran sodium sulfate (DSS)-induced mice and the underlying relationship with molecular characteristics. Fumaric acid (FMA), isoliquiritigenin (ISO), cinnamaldehyde (CA), ferulic acid (FA), sulforaphane (SFN), and chlorogenic acid (CGA) exhibited varying improvements in colitis on clinical signs, colonic histopathology, inflammatory and oxidative indicators, and Nrf2 pathway in a sequence of SFN, ISO > FA, CA > FMA, CGA. Representative molecular characteristics of the “penetration-affinity−covalent binding” procedure, logP value, Keap1 affinity energy, and electrophilic index of FECs were theoretically calculated, among which logP value revealed a strong correlation with colitis improvements, which was related to the expression of Nrf2 and its downstream proteins. Above all, SFN and ISO possessed high logP values and effectively improving DSS-induced colitis by activating the Keap1−Nrf2 pathway to alleviate oxidative stress and inflammatory responses.

Keywords: colitis; electrophilic compound; logP; molecular characteristic.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Structures of the investigated FECs.
Figure 2
Figure 2
Flow chart of experimental design.
Figure 3
Figure 3
Effects of FECs on weight change, DAI score, colonic shortening and splenic index in DSS-induced mice. (A) Body weight changes; (B) DAI scores at the end; (C) Images of the colon length; (D) Colon length; (E) Spleen index. Data are expressed as mean ± SD (n = 8). # p < 0.05, ## p < 0.01, ### p < 0.001, compared with the CON group; * p < 0.05, ** p < 0.01; *** p < 0.001, compared with the DSS group.
Figure 4
Figure 4
Effect of FECs supplementation on histopathological changes by H&E staining in DSS-induced mice colon, ×200 magnifications. (A) CON group; (B) DSS group; (C) FMA group; (D) ISO group; (E) CA group; (F) FA group; (G) SFN group; (H) CGA group. Inflammatory cells infiltration (red circle), crypt structure damage (red arrow), upper mucosa deformation (yellow triangle), submucosa edema (red star).
Figure 5
Figure 5
Molecular docking of FECs and BTB domain of Keap1. (A) FMA; (B) ISO; (C) CA; (D) FA; (E) SFN; (F) CGA.
Figure 6
Figure 6
Effect of FECs on inflammatory and oxidative factors in colon tissue of mice with colitis. (A) TNF-α; (B) IL-1β; (C) IL-6; (D) T-AOC; (E) GSH-px; (F) MPO; (G) MDA; (H) SOD. Data are expressed as mean ± SD (n = 8). # p < 0.05, ## p < 0.01, ### p < 0.001 compared with the CON group; * p < 0.05, ** p < 0.01; *** p < 0.001, compared with the DSS group.
Figure 7
Figure 7
The mRNA and protein expression levels of the Nrf2 pathway in colon tissue of mice with colitis. mRNA expression of (A) Nrf2; (B) NQO1; (C) HO-1; (D) Western blotting of Nrf2, HO-1 and NQO1; Relative protein expression of (E) Nrf2; (F) HO-1; (G) NQO1. Data are expressed as mean ± SD (n = 8). # p < 0.05, ## p < 0.01, ### p < 0.001, compared with the CON group; * p < 0.05, ** p < 0.01; *** p < 0.001, compared with the DSS group.
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