Hyuck-Se Kwon

3,3′‐diindolylmethane attenuates colonic inflammation and tumorigenesis in mice

Background: 3,3‐Diindolylmethane (DIM) is a major in vivo product of acid‐catalyzed oligomerization of indole‐3‐carbinol (I3C) derived from Brassica food plants. Although DIM is known as a chemopreventive and chemotherapeutic phytochemical, the effects of DIM on inflammation in vivo are still unknown. In the present study we investigated the antiinflammatory effects of DIM on experimental colitis and colitis‐associated colorectal carcinogenesis. Methods: To determine if DIM has an antiinflammatory effect in vivo, we examined the therapeutic effects of DIM in dextran sodium sulfate (DSS)‐induced experimental colitis and colitis‐associated colon carcinogenesis induced by azoxymethane (AOM)/DSS in BALB/c mice. Results: Treatment with DIM significantly attenuated loss of body weight, shortening of the colon, and severe clinical signs in a colitis model. This was associated with a remarkable amelioration of the disruption of the colonic architecture and a significant reduction in colonic myeloperoxidase activity and production of prostaglandin E2, nitric oxide, and proinflammatory cytokines. Further, DIM administration dramatically decreased the number of colon tumors in AOM/DSS mice. Conclusions: These results suggest that DIM‐mediated antiinflammatory action at colorectal sites may be therapeutic in the setting of inflammatory bowel disease and colitis‐associated colon cancer. (Inflamm Bowel Dis 2009)

Glabridin, a functional compound of liquorice, attenuates colonic inflammation in mice with dextran sulphate sodium‐induced colitis

Inflammatory bowel disease (IBD) is characterized by detrimental immune reactivity in the gut, and the imbalance between proinflammatory and anti‐inflammatory reactivity. The aims of this study were to determine whether oral administration of glabridin, a functional component of liquorice, could ameliorate dextran sulphate sodium (DSS)‐induced colitis, as well as to understand the possible underlying mechanisms. Acute experimental colitis was induced in BALB/c mice by treatment with 5% DSS for 7 days. Glabridin (10 or 50 mg/kg/day) was given for 7 days. Treatment with glabridin significantly attenuated mortality, loss of body weight, shortening of the colon and severe clinical symptoms. This was associated with a remarkable amelioration of the disruption of the colonic architecture, a significant reduction in colonic myeloperoxidase (MPO) activity and the production of inflammatory mediators such as nitric oxide (NO), prostaglandin (PG) E2, and proinflammatory cytokines. These results suggest that glabridin‐mediated anti‐inflammatory action on colorectal sites may be a useful therapeutic approach to IBD.

Chrysin, a natural flavone, improves murine inflammatory bowel diseases

Chrysin (5,7-dihydroxyflavone) is a natural flavone commonly found in many plants. It has previously been shown to be an anti-tumor agent. In this study, we investigated whether chrysin could alleviate the symptoms of dextran sodium sulfate (DSS)-induced colitis in mice and whether chrysin has an inhibitory effect on nuclear factor (NF)-kappaB activation in vitro. A significant blunting of weight loss and clinical signs was observed in DSS-exposed, chrysin-treated mice when compared to vehicle-treated mice. This was associated with a remarkable amelioration of the disruption of the colonic architecture, a significant reduction in colonic myeloperoxidase (MPO) activity, and a decrease in the production of inflammatory mediators such as nitric oxide (NO), prostaglandin (PG) E(2), and pro-inflammatory cytokines. In addition, chrysin inhibited tumor necrosis factor (TNF)-alpha-induced activation of NF-kappaB in IEC-6 cells. These findings suggest that chrysin exerts potentially clinically useful anti-inflammatory effects mediated through the suppression of NF-kappaB activation.

Licochalcone A isolated from licorice suppresses lipopolysaccharide-stimulated inflammatory reactions in RAW264.7 cells and endotoxin shock in mice

Licochalcone A (LicA), a major phenolic constituent of the licorice species Glycyrrhiza inflata, exhibits various biological properties, including chemopreventive, anti-bacterial, and anti-spasmodic activity. We report that LicA inhibits inflammatory reactions in macrophages and protects mice from endotoxin shock. Our in vitro experiments showed that LicA suppressed not only the generation of nitric oxide (NO) and prostaglandin (PG)E2, but also the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 induced by lipopolysaccharide (LPS) in RAW264.7 cells. Similarly, LicA inhibited the production of inflammatory cytokines induced by LPS in RAW264.7 cells, including IL-1β and IL-6. In an animal model, LicA protected BALB/c mice from LPS-induced endotoxin shock, possibly through inhibiting the production of inflammatory cytokines and NO. Collectively, LicA inhibited the production of inflammatory mediators and may be a potential target for treatment of various inflammatory diseases.

Vaccinium uliginosum L. Improves Amyloid β Protein-Induced Learning and Memory Impairment in Alzheimer's Disease in Mice.

The present study investigated the effects of Vaccinium uliginosum L. (bilberry) on the learning and memory impairments induced by amyloid-β protein (AβP) 1-42. ICR Swiss mice were divided into 4 groups: the control (Aβ40-1A), control with 5% bilberry group (Aβ40-1B), amyloid β protein 1-42 treated group (Aβ1-42A), and Aβ1-42 with 5% bilberry group (Aβ1-42B). The control was treated with amyloid β-protein 40-1 for placebo effect, and Alzheimer’s disease (AD) group was treated with amyloid β-protein 1-42. Amyloid β-protein 1-42 was intracerebroventricular (ICV) micro injected into the hippocampus in 35% acetonitrile and 0.1% trifluoroacetic acid. Although bilberry added groups tended to decrease the finding time of hidden platform, no statistical significance was found. On the other hand, escape latencies of AβP injected mice were extended compared to that of Aβ40-1. In the Probe test, bilberry added Aβ1-42B group showed a significant (P<0.05) increase of probe crossing frequency compared to Aβ1-42A. Administration of amyloid protein (Aβ1-42) decreased working memory compared to Aβ40-1 control group. In passive avoidance test, bilberry significantly (P<0.05) increased the time of staying in the lighted area compared to AD control. The results suggest that bilberry may help to improve memory and learning capability in chemically induced Alzheimer’s disease in experimental animal models.