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Green Tea Polyphenols and Sulfasalazine have Parallel Anti-Inflammatory Properties in Colitis Models.

Oz HS, Chen T, de Villiers WJ - Front Immunol (2013)

Bottom Line: The inflammatory markers TNFα (3-fold), IL-6 (14-fold), and serum amyloid A (40-fold) increased in colitic animals and significantly decreased with treatment regiments.EGCG additionally reduced leptin levels (p < 0.01) while GrTP and sulfasalazine had no effect on leptin levels (p < 0.05).GrTP and EGCG improved antioxidants levels and attenuated severity of colitis analogous to sulfasalazine.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, University of Kentucky Medical Center , Lexington, KY , USA.

ABSTRACT

Background: There is no cure for autoimmune chronic inflammatory bowel disease (IBD). IBD patients commonly use complementary and alternative medications of which the safety, efficacy, and interaction with standard-of-care therapies are not fully known. Thus the consequences can become life-threatening. Sulfasalazine commonly used in IBD, potentially has severe adverse effects, including infertility, pulmonary fibrosis, lack of response, and ultimately patients may require intestinal resection. We hypothesized that green tea polyphenols (GrTP, EGCG) and sulfasalazine have similar anti-inflammatory properties.

Methods: BALB/c mice received Dextran sodium sulfate (DSS) to induce colitis (ulcerative colitis model). Exposure of IL-10 deficient mice (BALB/c-background) to normal microbiota provoked enterocolitis (mimics Crohn's disease). Animals were treated with agents incorporated into daily diets. Control animals received sham treatment.

Results: DSS-treated animals developed severe bloody diarrhea and colitis (score 0-4, 3.2 ± 0.27). IL-10 deficient mice developed severe enterocolitis as manifested by diarrhea, rectal prolapse, and colonic lesions. Animals tolerated regimens (GrTP, EGCG, sulfasalazine) with no major side effects, and further developed less severe colitis. IL-10 deficient animals became moribund on high dose, while tolerated low and Mid doses with significant improved symptoms of enterocolitis. GrTP, EGCG, and sulfasalazine significantly ameliorated colonic damage and histological scores in treated animals in a similar manner (GrTP vs. DSS p < 0.05; EGCG, sulfasalazine vs. DSS p < 0.01). The inflammatory markers TNFα (3-fold), IL-6 (14-fold), and serum amyloid A (40-fold) increased in colitic animals and significantly decreased with treatment regiments. In contrast, circulatory leptin levels decreased in colitic animals (twofold). EGCG additionally reduced leptin levels (p < 0.01) while GrTP and sulfasalazine had no effect on leptin levels (p < 0.05). Hepatic and colonic antioxidants were significantly depleted in colitic animals and treatment regiments significantly restored antioxidants levels.

Conclusion: GrTP and EGCG improved antioxidants levels and attenuated severity of colitis analogous to sulfasalazine. Future studies will reveal whether polyphenols can become an alternative/additive therapy for IBD therapy in humans.

No MeSH data available.


Related in: MedlinePlus

IL-10 deficient mice when exposed to the normal colonic microbiota (Sham-Control) developed enterocolitis in conventional environment. (A) IL-10 deficient mice became anemic with low hematocrit (Sham-Control) and GrTP significantly improved hematocrit in treated animals. (B) IL-10 deficient mice had enlarged splenic tissue due to infiltration of inflammatory cells and GrTP significantly reduced the inflammatory response. (C) IL-10 deficient mice developed spontaneous enterocolitis and rectal prolapsed. GrTP significantly ameliorated the pathological scores.
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Figure 5: IL-10 deficient mice when exposed to the normal colonic microbiota (Sham-Control) developed enterocolitis in conventional environment. (A) IL-10 deficient mice became anemic with low hematocrit (Sham-Control) and GrTP significantly improved hematocrit in treated animals. (B) IL-10 deficient mice had enlarged splenic tissue due to infiltration of inflammatory cells and GrTP significantly reduced the inflammatory response. (C) IL-10 deficient mice developed spontaneous enterocolitis and rectal prolapsed. GrTP significantly ameliorated the pathological scores.

Mentions: We further examined efficacy of GrTP against enterocolitis in IL-10 deficient mice exposed to normal gut microbiota. Animals became anemic (Figure 5A) and showed increased colonic weight (309 ± 39) and splenic length (1.7 ± 0.05) due to accumulation of inflammatory cells and enterocolitis (Figure 5B). IL-10 deficient animals tolerated Low and Mid doses of GrTP with significant improvement in their enterocolitis symptoms for the duration of experiment. While, animals on High dose lost weight and became moribund and were terminated. GrTP significantly improved anemia, decreased colonic weight (254 ± 17), and normalized splenic length (1.5 ± 0.04 p < 0.05). In addition, IL-10 deficient mice had significantly high SAA (100 times) and IL-1β (200 times) compared to those kept at transgenic conditions. GrTP had no significant effect on IL-1β with a partial effect on SAA in this model (data not shown).


Green Tea Polyphenols and Sulfasalazine have Parallel Anti-Inflammatory Properties in Colitis Models.

Oz HS, Chen T, de Villiers WJ - Front Immunol (2013)

IL-10 deficient mice when exposed to the normal colonic microbiota (Sham-Control) developed enterocolitis in conventional environment. (A) IL-10 deficient mice became anemic with low hematocrit (Sham-Control) and GrTP significantly improved hematocrit in treated animals. (B) IL-10 deficient mice had enlarged splenic tissue due to infiltration of inflammatory cells and GrTP significantly reduced the inflammatory response. (C) IL-10 deficient mice developed spontaneous enterocolitis and rectal prolapsed. GrTP significantly ameliorated the pathological scores.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672863&req=5

Figure 5: IL-10 deficient mice when exposed to the normal colonic microbiota (Sham-Control) developed enterocolitis in conventional environment. (A) IL-10 deficient mice became anemic with low hematocrit (Sham-Control) and GrTP significantly improved hematocrit in treated animals. (B) IL-10 deficient mice had enlarged splenic tissue due to infiltration of inflammatory cells and GrTP significantly reduced the inflammatory response. (C) IL-10 deficient mice developed spontaneous enterocolitis and rectal prolapsed. GrTP significantly ameliorated the pathological scores.
Mentions: We further examined efficacy of GrTP against enterocolitis in IL-10 deficient mice exposed to normal gut microbiota. Animals became anemic (Figure 5A) and showed increased colonic weight (309 ± 39) and splenic length (1.7 ± 0.05) due to accumulation of inflammatory cells and enterocolitis (Figure 5B). IL-10 deficient animals tolerated Low and Mid doses of GrTP with significant improvement in their enterocolitis symptoms for the duration of experiment. While, animals on High dose lost weight and became moribund and were terminated. GrTP significantly improved anemia, decreased colonic weight (254 ± 17), and normalized splenic length (1.5 ± 0.04 p < 0.05). In addition, IL-10 deficient mice had significantly high SAA (100 times) and IL-1β (200 times) compared to those kept at transgenic conditions. GrTP had no significant effect on IL-1β with a partial effect on SAA in this model (data not shown).

Bottom Line: The inflammatory markers TNFα (3-fold), IL-6 (14-fold), and serum amyloid A (40-fold) increased in colitic animals and significantly decreased with treatment regiments.EGCG additionally reduced leptin levels (p < 0.01) while GrTP and sulfasalazine had no effect on leptin levels (p < 0.05).GrTP and EGCG improved antioxidants levels and attenuated severity of colitis analogous to sulfasalazine.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, University of Kentucky Medical Center , Lexington, KY , USA.

ABSTRACT

Background: There is no cure for autoimmune chronic inflammatory bowel disease (IBD). IBD patients commonly use complementary and alternative medications of which the safety, efficacy, and interaction with standard-of-care therapies are not fully known. Thus the consequences can become life-threatening. Sulfasalazine commonly used in IBD, potentially has severe adverse effects, including infertility, pulmonary fibrosis, lack of response, and ultimately patients may require intestinal resection. We hypothesized that green tea polyphenols (GrTP, EGCG) and sulfasalazine have similar anti-inflammatory properties.

Methods: BALB/c mice received Dextran sodium sulfate (DSS) to induce colitis (ulcerative colitis model). Exposure of IL-10 deficient mice (BALB/c-background) to normal microbiota provoked enterocolitis (mimics Crohn's disease). Animals were treated with agents incorporated into daily diets. Control animals received sham treatment.

Results: DSS-treated animals developed severe bloody diarrhea and colitis (score 0-4, 3.2 ± 0.27). IL-10 deficient mice developed severe enterocolitis as manifested by diarrhea, rectal prolapse, and colonic lesions. Animals tolerated regimens (GrTP, EGCG, sulfasalazine) with no major side effects, and further developed less severe colitis. IL-10 deficient animals became moribund on high dose, while tolerated low and Mid doses with significant improved symptoms of enterocolitis. GrTP, EGCG, and sulfasalazine significantly ameliorated colonic damage and histological scores in treated animals in a similar manner (GrTP vs. DSS p < 0.05; EGCG, sulfasalazine vs. DSS p < 0.01). The inflammatory markers TNFα (3-fold), IL-6 (14-fold), and serum amyloid A (40-fold) increased in colitic animals and significantly decreased with treatment regiments. In contrast, circulatory leptin levels decreased in colitic animals (twofold). EGCG additionally reduced leptin levels (p < 0.01) while GrTP and sulfasalazine had no effect on leptin levels (p < 0.05). Hepatic and colonic antioxidants were significantly depleted in colitic animals and treatment regiments significantly restored antioxidants levels.

Conclusion: GrTP and EGCG improved antioxidants levels and attenuated severity of colitis analogous to sulfasalazine. Future studies will reveal whether polyphenols can become an alternative/additive therapy for IBD therapy in humans.

No MeSH data available.


Related in: MedlinePlus