Health-Promoting Properties of Proanthocyanidins for Intestinal Dysfunction

Abstract

The intestinal barrier is constantly exposed to potentially harmful environmental factors, including food components and bacterial endotoxins. When intestinal barrier function and immune homeostasis are compromised (intestinal dysfunction), inflammatory conditions may develop and impact overall health. Evidence from experimental animal and cell culture studies suggests that exposure of intestinal mucosa to proanthocyanidin (PAC)-rich plant products, such as grape seeds, may contribute to maintaining the barrier function and to ameliorating the pathological inflammation present in diet-induced obesity and inflammatory bowel disease. In this review, we aim to update the current knowledge on the bioactivity of PACs in experimental models of intestinal dysfunction and in humans, and to provide insights into the underlying biochemical and molecular mechanisms.

Keywords: IBD; condensed tannin; flavan-3-ol; flavonoid; gut; inflammation; metabolic endotoxemia; obesity; permeability; procyanidin.

Figure 1

Dysfunctional intestinal mucosal. Chronic exposition to detrimental environmental stimuli, including several food components, may lead to dysbiosis, mucus layer depletion, and breakdown of the epithelial barrier. Constitutive stimulation of NF-κB signaling by bacterial endotoxins induce overproduction of pro-inflammatory cytokines and reactive species of oxygen and nitrogen, feeding back the epithelial barrier disruption and immune cell infiltration.

Figure 2

Chemical structures of proanthocyanidins (PACs). Flavan-3-ol monomers differ based on the hydroxylation pattern and their cis- or trans- configuration. Dimers A1/A2 and B1/B2 are shown as example of A- and B-type PACs, respectively.

Figure 3

Molecular mechanisms implicated in the physiological effects of PAC in the intestinal mucosa. PACs suppress inflammation interacting with bacterial endotoxins, as well as protein receptors, kinases and transcription factors involved in the pro-inflammatory signaling (NF-κB and mitogen-activated protein kinases (MAPK) pathways). Oxidative stress is mitigated directly by free-radical scavenging and indirectly by the activation of factor-erythroid-2-related factor 2 (NRF2), leading to antioxidant enzyme production via antioxidant responsive element (ARE) binding.