Colonic Coffee Phenols Metabolites, Dihydrocaffeic, Dihydroferulic, and Hydroxyhippuric Acids Protect Hepatic Cells from TNF-α-Induced Inflammation and Oxidative Stress.

Coffee presents beneficial health properties, including antiobesity effects. However, its effects on inflammation are controversial. Hydroxycinnamic acids are the main coffee phenolic bioactive compounds. In human bioavailability studies carried out with coffee, among the most abundant compounds found in urine and plasma were the colonic metabolites, dihydrocaffeic (DHCA), dihydroferulic (DHFA), and hydroxyhippuric (HHA) acids. To understand the hepato-protective potential of these three compounds, we tested whether treatment with realistic concentrations (0.5-10 µM) were effective to counteract inflammatory process and oxidative status induced by tumor necrosis factor α (TNF-α). First, we established a novel model of inflammation/oxidation using TNF-α and HepG2 cells. Afterwards, we evaluated the activity of DHCA, DHFA, and HHA against the inflammatory/oxidative challenge through the determination of the inflammatory mediators, interleukins (IL)-6, and IL-8 and chemokines, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1, as well as the levels of biomarkers of oxidative stress, such as reactive oxygen species, reduced glutathione, and the antioxidant enzymes glutathione peroxidase and reductase. Results showed that all three compounds have a potential hepato-protective effect against the induced inflammatory/oxidative insult.

Main Colonic Metabolites from Coffee Chlorogenic Acid May Counteract Tumor Necrosis Factor-α-Induced Inflammation and Oxidative Stress in 3T3-L1 Cells.

Obesity is coupled with an altered redox state and low-level inflammation. Oxidative stress may increase pre-adipocyte proliferation, adipocyte differentiation and mature adipocyte size. Regarding inflammation, the dysregulation of cytokine production by adipose tissue takes place in obesity, which is promoted by oxidative stress. Polyphenols may exert a positive effect on obesity, not only by modulating the redox state, but also due to their anti-inflammatory activity. Coffee, which is one of the most consumed beverages, is very rich in phenolic compounds. Bioavailability studies on coffee phenols have shown that the most abundant group of metabolites in plasma and urine are dihydrocaffeic (DHCA), dihydroferulic (DHFA), and hydroxyhippuric (HHA) acids, the three acids of colonic origin. To better understand the antioxidant and anti-inflammatory properties of DHCA, DHFA, and HHA, an inflammation/oxidation model was set up in the pre-adipocyte 3T3-L1 cell line using tumor necrosis factor-α (TNF-α). After the exposure of 3T3-L1 cells to 0.5, 1, 5, and 10 µM of TNF-α at different times, the cell viability, interleukin (IL)-6 secretion, and the production of reactive oxygen species (ROS) and glutathione (GSH) were determined. Using the TNF-α prooxidant and proinflammatory conditions established (10 µM, 24 h), it was observed that the physiological concentrations (0.5, 1, 5, and 10 µM) of DHCA, DHFA, and HHA induced dose-dependent antioxidant effects according to the ROS, GSH, and antioxidant enzyme (glutathione peroxidase) results. In addition, reductions in the IL-1ß, IL-6, and monocyte chemoattractant protein-1 (MCP-1) concentrations were observed to different extents depending on the metabolite (DHFA, HHA, or DHCA) and the concentration used. In conclusion, the main colonic metabolites from coffee chlorogenic acids may counteract TNF-α-induced inflammation and oxidative stress in the 3T3-L1 cell line, and thus, they present antiobesity potential.