Oxidative Medicine and Cellular Longevity / 2016 / Article / Tab 4

Review Article

Bioactivity of Polyphenols: Preventive and Adjuvant Strategies toward Reducing Inflammatory Bowel Diseases—Promises, Perspectives, and Pitfalls

Table 4

Animal trials suggesting positive health benefits of polyphenols with respect to IBD—an overview.

Aspects studiedDosing and timeEffects foundMechanism proposed and criticsReference

Effect of green tea PP on DSS induced colitis in IL-2 deficient miceWater with 5 g/L green tea PP for 6 weeksReduced serum amyloid A, increased weight gain & hematocrit, reduced IFN-, TNF- in cultured cells from colonAnti-inflammatory effects of green tea PP[84]

Effect of green tea PP & other antioxidants on DSS induced colitis in mice10 d, no dose specified Lengthening of colon, enhanced blood level of reduced GSH, improved serum amyloid A, TNF-, improved cytoskeletonImproved antioxidant status [85]

Effect of ellagic acid (EA) on rats with TBNS induced colitis10-11 rats per group receiving 10–20 mg/kg EA for 10 dEA decreased neutrophil infiltration & COX-2 & iNOS. Reduced activation of p38, JNK & ERK1/2 MAPKs, preventing inhibitory protein IB-degradation, inhibiting nuclear translocation of p65EA diminished severity & extension of intestinal injuries. EA also increased mucus production in goblet cells in colon mucosa[86]

Effect of strawberry PP on rats with induced gastric lesions40 mg/kg with various strawberries or quercetin (100 mg/kg) for 10 d (equiv. to 0.5 kg for 70 kg adult)Reduced MDA, enhanced SOD & in part CAT in gastric mucosa. Antioxidant enzyme activities increased with strawberry extract, decreased gastric lipid peroxidation. Sign. correlation between total anthocyanin content &  % inhibition of ulcer[87]

Effect of apple PP (APP) on mice with induced colitisAPP at 1% added to drinking water (90% tannins) for up to 4 weeksAPP administration dampened mRNA expression of IL-1, TNF-, IL-6, IL-17, IL-22, CXCL9, CXCL10, CXCL11, & IFN- in colon APP-mediated protection required T cells. Giving APP during colitis to T-cell receptor (−/−) mice enhanced proinflammatory cytokine expression, showing need for TCR cells in APP-mediated protection[88]

Effect of ellagic acid (EA) & enriched pomegranate extract (PE) in TBNS induced rats6 weeks with either 250 or 500 mg/kg PE, or 10 mg/kg EA, or both togetherMPO activity & TNF- levels were significantly reduced in rats receiving PPPE & EA-enriched PE diets decreased COX-2 & iNOS expression, reduced MAPK phosphorylation & prevented NF-B translocation[63]

Effect of EGCG & Piper nigrum on DSS induced colitis in mice6.9 mg/kg bw. EGCG or Piper nigrum (2.9 mg/kg) for 60 dCombination of EGCG & piperine sign. reduced loss of bw., improved clinical course, & increased overall survivalAttenuated colitis was associated with reduced histological damage to colon & reduction of tissue concentrations of MDA. Neutrophil accumulation indicator MPO was reduced in the colon; SOD & GPx were increased[89]

Effect of green tea PP on DSS induced colitis in IL-10 deficient miceGreen tea PP or EGCG at 0.25, 0.5, & 1% added to diet for 10 weeksLow dose improved histopathology; all doses improved antioxidant levels (colonic & hepatic GSH), reduction of circulating TNF-α  & IL-6Antioxidant activities of polyphenols[58]

Effect of grape juice on rats with TBNS induced colitis1 or 2% grape juice in diet for up to 9 d1% grape juice improved clinical symptoms of colitis: reduced intensity of macroscopic & histological scoresSig. differences of TNF-  & inducible NO synthase mRNA expression [90]

Effect of oligonol (lychee PP) on mice with DSS induced colitis0.5 or 5 mg/kg/d for 2 weeksOligonol sign. inhibited activation of NF-B, STAT3, COX-2, iNOS & cyclin D1 in the colon. It also inhibited adenoma formation & attenuated MDA levels & protein oxidation (4-hydroxy-2-nonenal)Various anti-inflammatory genes involved, as well as effects on antioxidant status[91]

Effects of Phlomis purpurea L. & Phlomis lychnitis L. on rats with DSS induced colitisP. lychnitis (10 & 20 mg/kg), P. purpurea (10 & 25 mg/kg) for 1 weekBoth extracts reduced colonic MPO activity, increased colonic GSH, & downregulated iNOS expression. Only P. purpurea extract reduced expression of IL-1β  & IL-17, CINC-1 & MCP-1, & ICAM-1Anti-inflammatory aspects of both extracts. Implication of NF-B?[92]

Effect of green tea PP on Mdr1a(−/−) mice on proteomic & transcriptomic endpoints0.6% in the diet for 12 weeksImproved histopathology, reduced abundance of transcripts & proteins associated with immune & inflammatory response/fibrinogenesis, increased abundance of pathways associated with xenobiotic metabolism in response to GrTP Anti-inflammatory activity mediated by multiple molecular pathways. PPAR-α  & STAT1 appear to be key molecules regulating these effects[93]

Effect of naringenin on DSS induced colitis mice0.3% naringenin in diet for up to 9 dNaringenin attenuated the increased DAI & colon shortening & suppressed the increased cytokine (IL-17A, IL-1, IL-6, MIP2 expression). Reduction of permeabilityAnti-inflammatory properties of naringenin & barrier protection[94]

Effect of grape seed & marc extract (GSME) on healthy pigsGSME at 1% added to diet in 6 pigs versus 6 control pigs for 4 weeksLower expression of NF-B (ICAM-1, ccl-2, IL-8, TNF-, SAA) & Nrf-2 (GPx-1, NQO-1, PRDX-6, SOD-1, TXNRD-1) target genes. No difference of conc. of plasma -tocopherol & TBARS in liver & plasma & total antioxidant capacity Pigs fed GSME diet had lower NF-B & Nrf-2 transactivation in duodenal mucosa. Ratio of villus height : crypt depth & the gain : feed ratio was higher in pigs fed GSGME[95]

Effect of catechin on rats receiving ketoprofenCatechin (35 mg/kg/d) for 21 dCatechin inhibited oxidative damage & reversed impairment of antioxidant system (GSH, LDH-leakage, 8-OHdG) in intestinal mucosaROS reduction by polyphenols[96]

Passiflora edulis peel rich in fiber/PP on TBNS induced colitis in rats7 d, no PP conc. of passion fruit stated. 25 g passion fruit flour/kg diet givenImproved serum FRAP, GPx, TBARS, GR, decreased colon lipid peroxidation, decreased no. of aerobic bacteria & Enterobacteria, improved acetic & butyric acid levels in feces, higher no. of Bifidobacteria & LactobacilliImproved antioxidant status, improved gut flora[97]

Effect of PP rich evening primrose pomace (EP) extract on TBNS induced colitis in mice10 mg/kg of 612 mg/g PP extract per dry basis, for 3 dImproved histopathology & MPO, reduced tissue hydrogen peroxide levels, no effect on IL-1, TNF-Reduced ROS via antioxidant activity[98]

PP-rich sorghum bran given to rats with DSS induced colitis6% fiber diet given over 21 dDiet significantly affected Bacteroidales, Bacteroides, Clostridiales, & LactobacillusProtection via improving microbial diversity & richness & dysbiosis of Firmicutes/Bacteroidetes[99]

Effect of grape seed PP in IL-10 deficient mice16 weeks of exposure with 1% GSP of dry food weightImproved histopathology, reduced pore forming claudin-2 protein, & increased barrier forming claudin-1 protein expressionReduced expression of NF-B, reduced beclin-1 & AMPK expression by GSE [100]

Effects of grape seed PP (GSP) in DSS induced colitis in rats21 d, 1.15 mg/g PP in dietReduced lesions (histological score) & disease activity index, reduced cytokines (IL-13, TNF-, IL-1, IL-10, GM-CSF, IL-6, IL-1, IF-), reduced MPO, enhanced GSH in colonic tissueUpregulation of various genes implicated in colitis such as intercellular adhesion molecule 1 (ICAM-1) & matrix metalloproteinase 9 (MMP-9)[101]

Effects of gallic acid on induced colitis in mice10 mg/kg for 7 d together with DSSImproved histology scores, reduced TNF-, IL-6, IL-1, IL-17, IFN- expression in colonic tissueReduced expression of p-STAT3, reduced expression of iNOS, COX-2, MPO in colon, reduction of p65-NF-B[102]

Effect of wheat anthocyanins on DSS induced colitis in miceNo dose specified. 14 d exposureNo sign. effects on colon length, bw., histopathology, markers of oxidative stress (FRAP, TAC, AOPP)Degradation of anthocyanins, unclear dose, too much focus on antioxidant effects only[103]

Effect of cranberry extract on miceC57BL/6J mice on high fat/high sucrose diet receiving either water or cranberry extract for 8 weeksMice receiving cranberry extract showed reduced intestinal oxidative stress & inflammationEnhanced population with Akkermansia (mucus-degrading, SCFA producing), prebiotic effect[104]

Effect of cacao extract on mice with DSS induced colitis5 & 10% cacao diets for 62 dInhibited proliferation of tumor epithelial cells, suppressed colonic IL-6, TNF-, IL-17, IL-1 expression Reduced expression & activation of STAT3, NF-B, reduced expression of Bcl-xl, CD68+, & MPO, enhanced caspase-3[105]

See footnote of Table 3.

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