Protocatechuic aldehyde is a polyphenol found in many plants and foods; it exhibits anti-inflammatory, cardioprotective, anti-atherosclerotic, and hepatoprotective activities. In animal models of ischemia/reperfusion, protocatechuic aldehyde decreases levels of creatine kinase-MB, troponin-1, TNF-α, IL-6, intracellular adhesion molecule 1 (ICAM-1), and inhibitor of κB kinase (IKK) and prevents activation of NF-κB, decreasing infarct size. Additionally, protocatechuic aldehyde decreases activity of high-mobility group box 1 (HMGB1) protein, decreasing levels of myeloperoxidase and activation of NF-κB and preventing sepsis in animal models. This compound also decreases activation of caspase 3 in endothelial cells, preventing apoptosis. In animal models of liver fibrosis, protocatechuic aldehyde decreases levels of collagen, TGF-β, and connective transforming growth factor (CTGF).