Bridging Tradition and Modern Medicine: Caffeic Acid as a Multifunctional Therapeutic Agent in 2025

Abstract

Background

Caffeic acid (CA), a naturally occurring hydroxycinnamic acid abundant in coffee, fruits, vegetables, and propolis, represents a molecular bridge between traditional herbal medicine and modern pharmacotherapy. Characterized by both an acrylic acid moiety and a phenolic hydroxyl group, CA and its derivatives—most notably caffeic acid phenethyl ester (CAPE)—exert a wide range of biological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, neuroprotective, and cardiometabolic effects. Both naturally isolated and chemically synthesized derivatives have also shown synergistic potential with antibiotics and other therapeutics, positioning CA as a promising multifunctional bioactive compound.

Objectives

This review consolidates recent advances (2022–2025) in understanding the pharmacological potential of caffeic acid, with emphasis on its molecular mechanisms of action, pharmacokinetic challenges, formulation strategies, and therapeutic relevance. Special focus is placed on antimicrobial applications, transcriptional regulation (Nrf2, NF-κB, STAT3), mitochondrial protection, and bioavailability-enhancing approaches, including nanotechnology and medicinal chemistry–driven modifications.

Conclusion

Current evidence highlights CA’s diverse pharmacological profile and its dual role as both a traditional remedy and a modern therapeutic candidate. Despite strong preclinical support, translation to clinical practice remains limited by issues of bioavailability, metabolism, and long-term safety. Future directions should prioritize mechanistic studies, synergistic drug-combination strategies, and structure–activity relationship optimization to unlock the full therapeutic potential of CA and its derivatives.