Polyphenol metabolites from colonic microbiota exert anti‐inflammatory activity on different inflammation models

Abstract

The polyphenols in fruits and vegetables may be partly responsible for the health-promoting effects attributed to fruit and vegetable intake. Although their properties have been relatively well studied, the activity of their metabolites, produced after ingestion, has been poorly investigated. Thus, the aim of this work was to study the potential anti-inflammatory effect of 18 polyphenol metabolites, derived from colon microbiota. They were screened by measuring prostaglandin E(2) (PGE(2)) production by CCD-18 colon fibroblast cells stimulated with IL-1beta. Metabolites that inhibited more than 50% PGE(2) production were hydrocaffeic (HCAF), dihydroxyphenyl acetic (dOHPA), and hydroferulic acid (HFER), that subsequently were tested with the writhing and paw pressure test in rodents where all three compounds showed an anti-inflammatory effect. The effect of HCAF administered orally (50 mg/kg) was also tested in the dextran sodium sulfate (DSS)-induced colitis model. Weight loss and fecal water content were more pronounced in DSS rats than in DSS-HCAF treated rats. HCAF treatment diminished the expression of the cytokines IL-1beta, IL-8, and TNF-alpha, reduced malonyldialdehyde (MDA) levels and oxidative DNA damage (measured as 8-oxo-2'-deoxyguanosine levels) in distal colon mucosa. These results indicate that HCAF, dOHPA, and HFER have anti-inflammatory activity in vitro and in vivo.

Phenylethanoid Glycosides: Research Advances in Their Phytochemistry, Pharmacological Activity and Pharmacokinetics

“…Pedicularioside A (118), leucosceptoside A (119), isoacteoside (120), acteoside (121), and arenariside (122) were studied to assess their effects on MPP + -induced cell death in rat mesencephalic neurons [59]. Compound 118 had the greatest neuroprotective effect among the five tested compounds.…”

“…For example, the hydrolyzing metabolites of 117 and 121, such as hydroxytyrosol (HT) and 3-hydroxyphenylpropionic acid (3-HPP), possessed antioxidant [116,117], neuroprotective [118][119][120], and anti-inflammatory activities [121,122]. Identification of 117's metabolites produced by human intestinal bacteria, biliary metabolites as well as urinary and fecal ones was reported.…”

Non-extractable polyphenols, a major dietary antioxidant: occurrence, metabolic fate and health effects

“…(2) An increase in the antioxidant capacity of caecal content and in the expression of endogenous antioxidant Table 2. Summary of biological effects described for polyphenol metabolites Metabolites Biological effect Reference (2 )-Epicatechin conjugates Effects on flow-mediated vasodilation in human subjects (72) 3-Phenylpropionic acid, 3-hydroxyphenylacetic acid, 3-hydroxyphenylpropionic acid COX-2 inhibition in HT-29 intestinal cells (73) 3,4-Dihydroxyphenylacetic acid, hydroferulic acid Anti-inflammatory activity in CDD-18 colon fibroblast cells (74) Hydrocaffeic acid Reduction of oxidative stress in DSS-treated rats (74) Urolithin A, urolithin B, dihydroferulic acid Protein glycation inhibition (75) Urolithin A, urolithin B Antiproliferative effects through change in the expression levels of growth factor receptors, oncogenes and tumour suppressors in Caco-2 intestinal cells (76) COX-2, cyclo-oxygenase-2; DSS, dextran sodium sulfate. systems, thus counteracting the tumour-promoting reactive oxygen species (ROS) present in the colon (84,85,89,90) .…”

Bioavailability of phenolic compounds in grape juice cv. Autumn Royal

“…The urinary excretion of phenolics reveals that colonic metabolites pass through the circulatory system prior to excretion (Larrosa et al, 2009). As phenolics are mostly excreted during 24 h following their ingestion, the excretion in 24-h urine should be directly related to the amounts ingested during the sampling and the previous day (Koli et al, 2010).…”