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 studied	Dosing and time	Effects found	Mechanism proposed and critics	Reference
Effect of green tea PP on DSS induced colitis in IL-2 deficient mice	Water with 5 g/L green tea PP for 6 weeks	Reduced serum amyloid A, increased weight gain & hematocrit, reduced IFN-, TNF- in cultured cells from colon	Anti-inflammatory effects of green tea PP	[84]
Effect of green tea PP & other antioxidants on DSS induced colitis in mice	10 d, no dose specified	Lengthening of colon, enhanced blood level of reduced GSH, improved serum amyloid A, TNF-, improved cytoskeleton	Improved antioxidant status	[85]
Effect of ellagic acid (EA) on rats with TBNS induced colitis	10-11 rats per group receiving 10–20 mg/kg EA for 10 d	EA decreased neutrophil infiltration & COX-2 & iNOS. Reduced activation of p38, JNK & ERK1/2 MAPKs, preventing inhibitory protein IB-degradation, inhibiting nuclear translocation of p65	EA 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 lesions	40 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 colitis	APP at 1% added to drinking water (90% tannins) for up to 4 weeks	APP 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 rats	6 weeks with either 250 or 500 mg/kg PE, or 10 mg/kg EA, or both together	MPO activity & TNF- levels were significantly reduced in rats receiving PP	PE & 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 mice	6.9 mg/kg bw. EGCG or Piper nigrum (2.9 mg/kg) for 60 d	Combination of EGCG & piperine sign. reduced loss of bw., improved clinical course, & increased overall survival	Attenuated 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 mice	Green tea PP or EGCG at 0.25, 0.5, & 1% added to diet for 10 weeks	Low dose improved histopathology; all doses improved antioxidant levels (colonic & hepatic GSH), reduction of circulating TNF-α  & IL-6	Antioxidant activities of polyphenols	[58]
Effect of grape juice on rats with TBNS induced colitis	1 or 2% grape juice in diet for up to 9 d	1% grape juice improved clinical symptoms of colitis: reduced intensity of macroscopic & histological scores	Sig. differences of TNF-  & inducible NO synthase mRNA expression	[90]
Effect of oligonol (lychee PP) on mice with DSS induced colitis	0.5 or 5 mg/kg/d for 2 weeks	Oligonol 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 colitis	P. lychnitis (10 & 20 mg/kg), P. purpurea (10 & 25 mg/kg) for 1 week	Both 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-1	Anti-inflammatory aspects of both extracts. Implication of NF-B?	[92]
Effect of green tea PP on Mdr1a(−/−) mice on proteomic & transcriptomic endpoints	0.6% in the diet for 12 weeks	Improved 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 mice	0.3% naringenin in diet for up to 9 d	Naringenin attenuated the increased DAI & colon shortening & suppressed the increased cytokine (IL-17A, IL-1, IL-6, MIP2 expression). Reduction of permeability	Anti-inflammatory properties of naringenin & barrier protection	[94]
Effect of grape seed & marc extract (GSME) on healthy pigs	GSME at 1% added to diet in 6 pigs versus 6 control pigs for 4 weeks	Lower 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 ketoprofen	Catechin (35 mg/kg/d) for 21 d	Catechin inhibited oxidative damage & reversed impairment of antioxidant system (GSH, LDH-leakage, 8-OHdG) in intestinal mucosa	ROS reduction by polyphenols	[96]
Passiflora edulis peel rich in fiber/PP on TBNS induced colitis in rats	7 d, no PP conc. of passion fruit stated. 25 g passion fruit flour/kg diet given	Improved 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 & Lactobacilli	Improved antioxidant status, improved gut flora	[97]
Effect of PP rich evening primrose pomace (EP) extract on TBNS induced colitis in mice	10 mg/kg of 612 mg/g PP extract per dry basis, for 3 d	Improved 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 colitis	6% fiber diet given over 21 d	Diet significantly affected Bacteroidales, Bacteroides, Clostridiales, & Lactobacillus	Protection via improving microbial diversity & richness & dysbiosis of Firmicutes/Bacteroidetes	[99]
Effect of grape seed PP in IL-10 deficient mice	16 weeks of exposure with 1% GSP of dry food weight	Improved histopathology, reduced pore forming claudin-2 protein, & increased barrier forming claudin-1 protein expression	Reduced expression of NF-B, reduced beclin-1 & AMPK expression by GSE	[100]
Effects of grape seed PP (GSP) in DSS induced colitis in rats	21 d, 1.15 mg/g PP in diet	Reduced 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 tissue	Upregulation 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 mice	10 mg/kg for 7 d together with DSS	Improved histology scores, reduced TNF-, IL-6, IL-1, IL-17, IFN- expression in colonic tissue	Reduced 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 mice	No dose specified. 14 d exposure	No 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 mice	C57BL/6J mice on high fat/high sucrose diet receiving either water or cranberry extract for 8 weeks	Mice receiving cranberry extract showed reduced intestinal oxidative stress & inflammation	Enhanced population with Akkermansia (mucus-degrading, SCFA producing), prebiotic effect	[104]
Effect of cacao extract on mice with DSS induced colitis	5 & 10% cacao diets for 62 d	Inhibited 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.