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Abstract
Cyanidin-3β-D-glycoside (C3G), which is widely distributed in herbal medicines and functional foods, exhibits anti-inflammatory, anti-oxidant, and anti-scratching behavioral effects. Orally administered C3G is metabolized to protocatechuic acid (PA) by gut microbiota. Therefore, we compared the anti-colitic effect of C3G to that of PA in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. Orally administered C3G and PA preventively and curatively ameliorated TNBS-induced colitis parameters, including macroscopic colitis score, colon shortening, and increase of myeloperoxidase activity. Treatment with C3G or PA also inhibited the expression of cyclooxygenase-2, inducible NO synthatase, IL-1β, IL-6, and TNF-α and the activation of NF-κB in the colon of mice with TNBS-induced colitis. Furthermore, these also inhibited lipopolysaccharide-induced NF-κB activation and TNF-α expression in peritoneal macrophages. The anti-colitic effect of PA was more effective than C3G. Orally administered PA more potently attenuate colitis than C3G by inhibiting NF-κB activation and the anti-colitic efficacy of C3G may be dependent on the biotransformation of C3G to PA by gut microbiota.
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Fig. 2.
Experimental protocol. (A) Preventative effect for TNBS-induced colitis in mice. (B) Curative effect for TNBS-induced colitis in mice.
Fig. 3.
The preventive effects of C3G and PA on TNBS-induced colitis in mice. (A) Effects on body weight. (B) Effects on colon length. (C) Effects on macroscopic colitis score. (D) Effects on colonic MPO activity. (E) Effects on TNF-α, IL-1β, and IL-6 expression. (F) Effects on COX2 expression. TNBS, except normal group (NOR, treated with vehicle alone), was intrarectally administered. Test agents (CON, vehicle alone; C10, 10 mg/kg; C20, 20 mg/kg; PA, 10 mg/kg; SS, 20 mg/kg sulfasalazine) were orally administered from the 3rd day before TNBS treatment to the 3rd day after TNBS treatment and sacrificed 18 h after the final administration of test agents. All values are means (n = 10). #P < 0.05, significantly different vs. normal group; ∗P < 0.05, significantly different vs. control group.
Fig. 4.
The curative effects of C3G and PA on TNBS-induced colitis in mice. (A) Effects on body weight. (B) Effects on colon length. (C) Effects on macroscopic colitis score. (D) Effects on colonic MPO activity. (E) Effects on TNF-α, IL-1β, and IL-6 expression. (F) Effects on COX2 and iNOS expression and NF-κB activation. TNBS, except normal group (NOR, treated with vehicle alone), was intrarectally administered. Test agents (CON, vehicle alone; C10, 10 mg/kg; C20, 20 mg/kg; PA, 10 mg/kg; SS, 20 mg/kg sulfasalazine) were orally administered for 3 days after TNBS treatment and sacrificed 18 h after the final administration of test agents. All values are means (n = 10). #P < 0.05, significantly different vs. normal group; ∗P < 0.05, significantly different vs. control group.
Fig. 5.
Effect of C3G and PA on NF-κB activation and TNF-α expression in LPS-stimulated peritoneal macrophages. Peritoneal macrophages (0.5 × 106 cells) were incubated with LPS in the absence or presence of C3G (C10, 10 μM; C20, 20 μM) or PA (P10, 10 μM) for 90 min (for NF-κB) or 20 h (for TNF-α). All data are shown as the mean ± S.D. (n = 3). #p < 0.05 vs. group treated without LPS and test agents. ∗p < 0.05 vs. group treated with LPS alone.
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