Anti-inflammatory and Antioxidant Effects of Flavonoid-Rich Fraction of Bergamot Juice (BJe) in a Mouse Model of Intestinal Ischemia/Reperfusion Injury - PubMed (original) (raw)

Anti-inflammatory and Antioxidant Effects of Flavonoid-Rich Fraction of Bergamot Juice (BJe) in a Mouse Model of Intestinal Ischemia/Reperfusion Injury

Daniela Impellizzeri et al. Front Pharmacol. 2016.

Erratum in

Abstract

The flavonoid-rich fraction of bergamot juice (BJe) has demonstrated anti-inflammatory and antioxidant activities. The aim of work was to test the beneficial effects of BJe on the modulation of the ileum inflammation caused by intestinal ischemia/reperfusion (I/R) injury in mice. To understand the cellular mechanisms by which BJe may decrease the development of intestinal I/R injury, we have evaluated the activation of signaling transduction pathways that can be induced by reactive oxygen species production. Superior mesenteric artery and celiac trunk were occluded for 30 min and reperfused for 1 h. The animals were sacrificed after 1 h of reperfusion, for both histological and molecular examinations of the ileum tissue. The experimental results demonstrated that BJe was able to reduce histological damage, cytokines production, adhesion molecules expression, neutrophil infiltration and oxidative stress by a mechanism involved both NF-κB and MAP kinases pathways. This study indicates that BJe could represent a new treatment against inflammatory events of intestinal I/R injury.

Keywords: Citrus bergamia; bergamot juice; cytokines; inflammation; ischemia; oxidative stress.

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Conflict of interest statement

Agrumaria Corleone had no role in study design, data collection and analysis, decision to publish, or preparation of the paper and the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer VB and DT, and handling Editor declared their shared affiliation, and the handling Editor states that the process nevertheless met the standards of a fair and objective review.

Figures

FIGURE 1

FIGURE 1

Effect of BJe on histological alteration of ileum tissue, and on survival rate. Histological features of normal gut tissue were found in ileum tissues from sham-operated mice (A,A1; see Histological Score, D). Distal ileum section from I/R-subjected mice showed inflammatory infiltration by PMNs, concentrated below the epithelial layer and edema of the distal portion of the villi (B,B1; see Histological Score, D). BJe treatment reduced I/R-induced organ injury (C,C1; see Histological Score, D). The figures are representative of at least three experiments performed on different experimental days. Survival was monitored for 24 h after SAO shock (E). BJe administration is able to reduce the mortality induced by I/R injury. Data are means ± SEM of 10 mice for each group. ∗∗ P < 0.01 vs. SHAM; ∗∗∗ P < 0.001 vs. SHAM; ## P < 0.01 vs. I/R; ### P < 0.001 vs. I/R. ND, not detectable.

FIGURE 2

FIGURE 2

Effect of BJe on cytokine release and neutrophil infiltration. TNF-α and Il-1β ileum levels were significantly elevated after 1 h of reperfusion in I/R subjected mice (A,B) compared to sham mice (A,B). BJe reduced TNF-α and IL-1β levels (A,B). In addition, neutrophil infiltration was measured by MPO assay. Increased MPO activity was found in I/R subjected mice compared to sham animals (C). BJe treatment was able to decrease MPO activity in a significant way (C). Data are means ± SEM of 10 mice for each group. ∗P < 0.05 vs. SHAM; #P < 0.05 vs. I/R.

FIGURE 3

FIGURE 3

Effect of BJe on MDA levels and MnSOD expression. Reperfusion of the ischemic splanchnic circulation leads to a profound increase in MDA levels in ileum tissues from I/R subjected mice treated with vehicle (A). MDA levels were reduced by BJe treatment (A). In addition, the expression of an antioxidant enzyme MnSOD, was also evaluated by western blot (B). The expression of MnSOD was increased in BJe treated mice compared to vehicle group (B). Basal expression was found in sham mice (B). A representative blot of lysates (B) obtained from 10 animals/group is shown, and densitometry analysis of all animals is reported. Data are means ± SEM of 10 mice for each group. ∗P < 0.05 vs. SHAM; #P < 0.05 vs. I/R.

FIGURE 4

FIGURE 4

Effect of BJe on adhesion molecules expression. Ileum sections taken from I/R subjected- mice showed positive staining for ICAM-1 (B,B1,G) and for P-selectin (E,E1,G) compared to sham-operated mice (A,A1,D, D1,G). The degree of positive staining for adhesion molecules was reduced in tissue sections from mice treated with BJe (C,C1,F,F1,G). The figures are representative of at least three experiments performed on different experimental days. Data are indicated as means ± SEM of 10 mice for each group. ∗∗∗P < 0.001 vs. SHAM; ###P < 0.001 vs. I/R. ND, not detectable.

FIGURE 5

FIGURE 5

Effect of BJe on NF-κB pathway. Representative western blots showing the effects of BJe on IκB-α degradation (A), NF-κB p65 translocation (B) and iNOS expression (C) after SAO shock. BJe treatment reduced IκB-α degradation (A), NF-κB p65 translocation (B) and iNOS expression (C). A representative blot of lysates (A,B) obtained from 10 animals/group is shown, and densitometry analysis of all animals is reported. The results in (A–C) are expressed as means ± SEM of 10 mice for each group. ∗P < 0.05 vs. SHAM; #P < 0.05 vs. I/R.

FIGURE 6

FIGURE 6

Effect of BJe on MAPKs pathway. Representative western blots showing the effects of BJe on p-JNK (A), and p-P38 expression (B) after I/R injury. I/R caused an increase in p-JNK (A), and p-P38 (B) expression. BJe treatment was not able to reduce p-JNK (A) but significantly decreased p-P38 expression (B). A representative blot of lysates (A, B) obtained from 10 animals/group is shown, and densitometry analysis of all animals is reported. The results in (A, B) are expressed as means ± SEM of 10 mice for each group. *P < 0.05 vs. SHAM; **P < 0.01 vs. SHAM; #P < 0.05 vs. I/R.

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