Bridging Tradition and Modern Medicine: Caffeic Acid as a Multifunctional Therapeutic Agent in 2025
Gulam Muheyuddeen, Dr Stuti Verma, Priyanka Yadav, Tanzeem Ahmad
Abstract and Figures
BackgroundCaffeic 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.ObjectivesThis 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. Specialfocus is placed on antimicrobial applications, transcriptional regulation (Nrf2, NF-κB, STAT3), mitochondrial protection, and bioavailability-enhancing approaches, including nanotechnology and medicinal chemistry–driven modifications.ConclusionCurrent 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.IntroductionPolyphenolic compounds are central to both traditional herbal medicine and modern nutraceutical research. Among these, caffeic acid (3,4-dihydroxycinnamic acid) has attracted growing attention due to its broad pharmacological spectrum and historical presence in herbal remedies. Traditionally, caffeic acid-rich plants (e.g., Echinacea, Salvia, Rosmarinus, and bee propolis) were employed for their tonic, antimicrobial, and anti-inflammatory properties. In modern biomedicine, mechanistic insights demonstrate CA’s ability to modulate redox signaling, inflammatory cascades, and oncogenic pathways. Its versatility, spanning antioxidant to anticancer effects, positions it as a unique candidate for bridging ethnopharmacology with evidence-based medicine.[132-136]Caffeic acid (CFA) is a natural phenolic compound (a secondary metabolite of plants), belonging to the family of hydroxycinnamic acids (HCAs).CFA is biosynthesized in plant tissues via the endogenous shikimate pathway, which is known to be responsible for the production of aromatic amino acids from glucose. Phenylalanine is a precursor for the synthesis of CFA. CFA can be found in many productsconsumed daily, such as coffee beans, green tea, tomatoes, potatoes, artichokes, carrots, lettuces, dark plums, cherries, gooseberries, blackcurrants, grapes, and herbs (basil, rosemary, oregano) (Fig. 1). CFA and other phenolic compounds are involved in plants’ defense mechanism against insects, pathogens, animals (biotic stresses), and environmental conditions, such as excess water, drought, low and high temperatures, salinity, heavy metals, and ultraviolet radiation (abiotic stresses). Numerous in vitroand in vivo studies have shown that CFA has many biological properties, including anti-inflammatory, anticancer, antibacterial, antiviral, antidiabetic, hepatoprotective, and cardio protectiveactivity.[1]The presence of a catechol group with a chain ActivitySource of Caffeic acid.
* THESE STATEMENTS HAVE NOT BEEN EVALUATED BY THE FOOD AND DRUG ADMINISTRATION. THIS IS NOT INTENDED TO DIAGNOSE, TREAT CURE OR PREVENT ANY DISEASE.