Ferulic acid may target MyD88-mediated pro-inflammatory signaling – Implications for the health protection afforded by whole grains, anthocyanins, and coffee

Higher dietary intakes of anthocyanins have been linked epidemiologically to decreased risk for metabolic syndrome, type 2 diabetes and cardiovascular events; clinical trials and rodent studies evaluating ingestion of anthocyanin-rich extracts confirm favorable effects of these agents on endothelial function and metabolic syndrome. However, these benefits of anthocyanins are lost in rats whose gut microbiome has been eliminated with antibiotic treatment – pointing to bacterial metabolites of anthocyanins as the likely protective agents. A human pharmacokinetic assessment of orally administered cyanidin-3-O-glucoside, a prominent anthocyanin, has revealed that, whereas this compound is minimally absorbed, ferulic acid (FA) is one of its primary metabolites that appears in plasma. FA is a strong antioxidant and phase 2 inducer that has exerted marked anti-inflammatory effects in a number of rodent and cell culture studies; in particular, FA is highly protective in rodent models of diet-induced weight gain and metabolic syndrome. FA, a precursor for lignan synthesis, is widely distributed in plant-based whole foods, mostly in conjugated form; whole grains are a notable source. Coffee ingestion boosts plasma FA owing to gastrointestinal metabolism of chlorogenic acid. Hence, it is reasonable to suspect that FA mediates some of the broad health benefits that have been associated epidemiologically with frequent consumption of whole grains, anthocyanins, coffee, and unrefined plant-based foods. The molecular basis of the anti-inflammatory effects of FA may have been clarified by a recent study demonstrating that FA can target the adaptor protein MyD88; this plays an essential role in pro-inflammatory signaling by most toll-like receptors and interleukin-1β. If feasible oral intakes of FA can indeed down-regulate MyD88-dependent signaling, favorable effects of FA on neurodegeneration, hypothalamic inflammation, weight gain, adipocyte and beta cell function, adiponectin secretion, vascular health, and cartilage and bone integrity can be predicted. Since FA is well tolerated, safe, and natural, it may have great potential as a protective nutraceutical, and clinical trials evaluating its effects are needed.