The Evolving Therapeutic Landscape of Gallic Acid: A Review of Mechanistic Insights and Clinical Potential

Abstract

Gallic acid (GA), a plant-derived phenolic compound, is evolving from a general antioxidant into a specific molecular modulator and a functional building block for advanced biomedical materials. This review synthesizes recent insights underpinned by GA's “redox duality”—its capacity to act as either a radical scavenger or a pro-oxidant. In metabolic disorders, GA reprograms cellular machinery by modulating the miR-709/Nrf2 axis, enhancing LDL clearance via LDLR/PCSK9, and targeting the incretin system. In oncology, GA exhibits context-dependent toxicity, acting as a selective pro-oxidant to induce apoptosis and synergizing with tyrosine kinase inhibitors (TKIs), though safety interactions require careful assessment. GA's expanded neuropharmacological profile includes mitigating ferroptosis via GPX4 rescue and acting as a positive allosteric modulator of Kv1.1 channels. It also potently inhibits the NLRP3 inflammasome in gouty arthritis. Beyond traditional pharmacology, recent studies highlight GA's emergence in material science, including the development of GA-based Metal-Organic Frameworks (MOFs) and functional hydrogels for osteoarthritis, kidney stone prevention, and wound healing. Despite broad bioactivity, poor bioavailability remains a significant challenge, necessitating innovative bioactive material design and rigorous clinical validation.