Review Article

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

Table 5

In vitro trials suggesting health benefits of polyphenols with respect to IBD—an overview.

Aspects studiedDosing and timeEffects foundMechanism proposed and criticsReference

Effect of phytolens (water-soluble extract of PP antioxidants from nonsoy legumes) on colonic (T84) & murine macrophage (RAW 264.7) cellsPhytolens (10–100 M/mL) exposed to T84 & RAW 264.7 cells, 4 h & 12 h of exposurePhytolens sign. attenuated apoptosis in T84 cells induced by ONOO. Phytolens did not directly affect T84 cell viability or induce apoptosis after 4 h or overnight exposure. RAW 264.7 cells exposed to phytolens displayed decreased cell viability & increased apoptosisPotential beneficial effects of phytolens on inflammation via attenuating induced apoptosis[106]

PP standards effects of Caco-2 cellsChrysin, ellagic acid, genistein, & EGCG (all 50 M) for 28 hChrysin & ellagic acid inhibited NF-B activity & genistein & resveratrol increased it. Mixed effects on IL-8 secretionAnti- & proinflammatory aspects of PP[107]

Effect of PP metabolites 3,4-dihydroxyphenyl-acetic acid (ES) & 3-(3,4-dihydroxy-phenyl)-propionic acid (PS) on LT97 colon cellsCells incubated with ES (0–18 M) & PS (0–90 M), metabolites of quercetin & chlorogenic acid/caffeic acid, respectively, up to 72 hPP metabolites did not affect cell number but sign. upregulated GSTT2 expression & decreased COX-2Intestinal metabolites showed anti-inflammatory properties[108]

Effect of red wine PP extract (from Lenoir grapes) on human colon-derived CCD-18 Co myofibroblasts cells0–100 g/mL GAE, for 24 hRed wine extract decreased mRNA expression of NF-B, ICAM-1, VCAM-1, & PECAM-1, in a dose dependent manner miR-126, a target region within the 3′-UTR of VCAM-1 mRNA, was increased at 100 g/mL[109]

Effect of PP-rich grape seed (GS) & grape marc (GM) on Caco-2 cells24 h with up to 2 mg/mL Decreased mRNA levels of NF-κB target genes IL-1, IL-8, MCP-1 & CXCL1 in Caco-2 cells. Unchanged mRNA levels of Nrf-2 target genes GPX-2, NQO1, CYP1A1 & UGT1A12 mg/mL ethanolic extracts dose-dependently reduced NF-κB transactivation. No effect of ethanolic extracts was observed on Nrf-2[110]

Effect of apple peel PP on Caco-2/15 cells250 g/mL apple peel PP for 24 hApple peel PP prevented Fe/ascorbate-mediated lipid peroxidation & counteracted LPS-mediated inflammation by downregulating cytokines (TNF-, IL-6) & PGE2 Downregulation of COX-2 & NF-κB. Also induction of Nrf-2[111]

Effect of red wine extract (RWE) (rich in catechin B1 & malvidin-3-glucoside) on HT-29 colon cells100–600 g/mL RWE extract (144 mg/g PP) for 24 h RWE suppressed IκB degradation & IL-8 production dose-dependently. It also inhibited increase of NO from iNOS & of protein tyrosine nitration (biomarker of nitrosative stress)RWE reduced NF-κB activation; COX-2 & iNOS[69]

Effect of catechin, theaflavin, malvidin, cyanidin & apigenin on human Int-407 cells treated with ketoprofen25 M (malvidin, cyanidin & apigenin) or 100 M (catechin & theaflavin) for 5 hCatechin sign. decreased levels of lipid peroxidation & ROS (MDA, DCF) & increased activity of intracellular antioxidant enzymes GPx, Gred, total sulfhydryl groups (TSH)ROS reduction of PP. WB analysis revealed that catechin stimulated a time-dependent increase in Nrf-2 & total HO-1 protein expression[96]

Effect of cyanidin-3-glucoside on HT-29 colon cells25 M cyanidin-3-glucoside, up to 24 hImproved NO, PGE2 & IL-8 production Improved iNOS & COX-2 expressions. No effect on NF-κB or p38 MAPK, but STAT1[112]

Effect of blueberry anthocyanin-rich extract on Caco-2 cellsUp to 100 g/mL up to 48 hReduced IL-1β levels in Caco-2 cellsReduced activation of NF-κB. 50 & 100 g mL−1 effective[113]

Effect of resveratrol on HT-29 colon cells25 M resveratrol, up to 24 hDecreasing levels of activated
STAT1 in nucleus. Also reduction of cytokine-stimulated activation of SAPK/JNK pathway
Downregulation of JAK-STAT pathway, though not counteracting cytokine-triggered negative feedback mechanism of STAT1 through p38 MAPK[114]

Plum & cabbage digesta: triple culture cell model: Caco-2/HT-29-MTX with THP-118 h of incubation following digestionReduction of IL-8 secretion by plum varieties Influences via NF-κB & Nrf-2[67]

See footnote of Table 3.