Caffeic acid

Antioxidant and anti-inflammatory; modulates arachidonic acid pathway involved in inflammatory joint conditions

Caffeic acid (3,4-dihydroxycinnamic acid) exerts potent antioxidant activity through direct radical scavenging, chelation of pro-oxidant metal ions (Fe2+, Cu2+), and upregulation of endogenous antioxidant enzymes (superoxide dismutase, catalase) via Nrf2/ARE pathway activation. Anti-inflammatory activity involves direct inhibition of 5-lipoxygenase (5-LOX) and modest COX-2 inhibition, reducing leukotriene and prostaglandin synthesis. The antidiabetic mechanism includes activation of AMPK in skeletal muscle and liver, which promotes GLUT4 translocation to the plasma membrane (increasing insulin-independent glucose uptake), inhibits hepatic gluconeogenesis by suppressing PEPCK and G6Pase expression, and reduces lipid accumulation in hepatocytes. Caffeic acid phenethyl ester (CAPE), a more bioavailable lipophilic derivative, inhibits IKK-beta directly, blocking NF-κB activation and reducing systemic inflammatory burden.