Baccharis dracunculifolia DC Hydroalcoholic Extract Improves Intestinal and Hippocampal Inflammation and Decreases Behavioral Changes of Colitis Mice

Abstract

The hydroalcoholic extract of B. dracunculifolia (HEBD) and its major compound p-coumaric acid were evaluated against the severity of intestinal inflammation and behavioral changes like depressive and anxious behavior in colitis mice. Colitis was induced in Swiss mice by oral dextran sulfate sodium (DSS) administration for five days. The mice received vehicle (10 ml/kg), HEBD (3, 30, or 300 mg/kg), or p-coumaric acid (15 mg/kg) orally, once a day for twelve days. Behavioral tests were performed on the 11^th and 12^th days after the beginning of the treatments. Moreover, the colon, cortex, and hippocampus were collected to analyze oxidative and inflammatory parameters. The treatment with HEBD (300 mg/Kg), but not p-coumaric acid, showed decreased disease activity index (DAI) values compared to the vehicle group and partially preserved the villi architecture and mucin levels. Furthermore, the HEBD increased the antioxidant defenses in the colon and hippocampus and reduced the myeloperoxidase activity and IL-6 levels in the colon from colitis mice. Colitis mice treated with HEBD did not show depressive-like behavior in the tail suspension test. HEBD reduced colon inflammation, while it maintains antioxidant defenses and mucin levels in this tissue. It may reduce neuropsychiatric comorbidities associated with colitis through its antioxidant effects.

Figure 1

HEBD, but not p-coumaric acid, reduces colitis severity (panels A and B and prevents the weight loss (panel C in DSS-induced colitis mice). (a): DAI score over the entire treatment period. (b): DAI values at the 13^th after the beginning of treatments. (c): Weight loss at the 13^th after the beginning of treatments. Colitis mice were treated with the vehicle (VEH: water plus 1% Tween-80, 10 ml/kg, p.o) or hydroalcoholic extract of B. dracunculifolia (HEBD: 3–300 mg/kg, p.o). The naïve group was composed of noncolitis mice treated with the vehicle. Results are presented as the means ± S.E.M. (n = 6). One-way (panels B and C) or two-way (panel C) ANOVA followed by Bonferroni's multiple comparisons test.  ^∗p < 0.05, ^∗ ∗p < 0.05,  and  ^{∗ ∗ ∗}p < 0.05 when compared to VEH.

Figure 2

HEBD reduces on histological changes in colon tissue from DSS-induced colitis mice. NV: naive (noncolitis mice treated with the vehicle, water plus 1% Tween-80, 10 ml/kg, p.o); VEH: colitis mice treated with the vehicle; HEBD: hydroalcoholic extract of B. dracunculifolia (300 mg/kg). The asterisks indicate edema and inflammatory infiltrate, and black arrows indicate reduced villus height and crypt depth.

Figure 3

HEBD increased the mucin staining by PAS method in colon tissue from DSS-induced colitis mice. Colitis mice were treated with the vehicle (VEH: water plus 1% Tween-80, 10 ml/kg, p.o) or hydroalcoholic extract of B. dracunculifolia (HEBD: 300 mg/kg, p.o). (a) Results are presented as the means ± S.E.M. (n = 6), one-way ANOVA followed by Bonferroni post-test. ^###p < 0.001 and^#p < 0.05 compared with the naive (noncolitis) group (NV). ^∗∗∗p < 0.0001 compared with the colitis group treated with the vehicle (VEH). (b) Microscopic representative image from each experimental. Arrows indicate positive points for mucin labeling (stained in pink).

Figure 4

HEBD changes behavioral parameters of colitis mice in the EPM test. Colitis mice were treated with the vehicle (VEH: water plus 1% Tween-80, 10 ml/kg, p.o) or hydroalcoholic extract of B. dracunculifolia (HEBD: 300 mg/kg, p.o). Results are presented as the means ± S.E.M. (n = 6). One-way ANOVA followed by Bonferroni's post-test. ^###p < 0.001 and ^#p < 0.05 compared with the naive (noncolitis) group (NV). ^∗p < 0.05 compared with the colitis group treated with the vehicle (VEH).

Figure 5

HEBD changes behavioral parameters of colitis mice in the TST. Colitis mice were treated with the vehicle (VEH: water plus 1% Tween-80, 10 ml/kg, p.o) or hydroalcoholic extract of B. dracunculifolia (HEBD: 300 mg/kg, p.o). Results are presented as the means ± S.E.M. (n = 6). One-way ANOVA followed by Bonferroni's post-test. ^∗∗∗p < 0.001 compared with the noncolitis mice (NAIVE) or the colitis group treated with HEBD.

Figure 6

HEBD has not changed the behavioral parameters of colitis mice in the OFT. Colitis mice were treated with the vehicle (VEH: water plus 1% Tween-80, 10 ml/kg, p.o) or hydroalcoholic extract of B. dracunculifolia (HEBD: 300 mg/kg, p.o). Results are presented as the means ± S.E.M. (n = 6). One-way ANOVA followed by Bonferroni's posttest. ^∗p < 0.05 and ^∗∗p < 0.01 compared with the noncolitis mice (NAIVE).

Figure 7

Effects of HEBD on TNF levels in colon (a), hippocampus (b), and cortex (c) of colitis mice. Colitis mice were treated with the vehicle (VEH: water plus 1% Tween-80, 10 ml/kg, p.o) or hydroalcoholic extract of B. dracunculifolia (HEBD: 300 mg/kg, p.o). Results are presented as the means ± S.E.M. (n = 6). One-way ANOVA followed by Bonferroni's posttest. ^#p < 0.05 compared with naïve (noncolitis) group, and ^∗p < 0.05 compared to colitis group treated with the vehicle.

Figure 8

Effects of HEBD on IL-6 levels in colon (a), hippocampus (b), and cortex (c) of colitis mice. Colitis mice were treated with the vehicle (VEH: water, 10 ml/kg, p.o) or hydroalcoholic extract of B. dracunculifolia (HEBD: 300 mg/kg, p.o). Results are presented as the means ± S.E.M. (n = 6). One-way ANOVA followed by Bonferroni's posttest. ^#p < 0.05 compared with naïve (noncolitis) group, and ^∗p < 0.05 compared with colitis group treated with the vehicle.