Anacardic acid as a promising natural antimicrobial agent: Mechanisms of action, biofilm inhibition, and advances in nano-encapsulation for enhanced therapeutic efficacy

Anacardic acid (AA), a phenolic lipid primarily found in Anacardium occidentale and related plants, exhibits promising antimicrobial activity, notably against biofilm-associated infections. AA disrupts bacterial membranes, inhibits vital metabolic pathways, and interferes with quorum sensing, making it effective against both planktonic and biofilm-forming bacteria such as Staphylococcus aureus , Streptococcus mutans , and methicillin-resistant S. aureus (MRSA). Its distinctive chemical structure, particularly the length and degree of unsaturation of its alkyl side chains, plays a critical role in antimicrobial potency. Higher unsaturation enhances membrane disruption and antibacterial effects, while structural modifications, including branching and derivatisation, improve bioavailability and efficacy. Despite its potent action, AA has limited solubility and stability; thus, advances in nano-encapsulation techniques and complexation with carriers like hydroxypropyl-β-cyclodextrin have improved its clinical potential. AA and its analogues not only disrupt biofilm architecture but also suppress bacterial metabolism and inhibit extracellular polymeric substance (EPS) production, key factors in biofilm resilience. AA-based coatings and formulations offer promising applications in biomedical devices to prevent biofilm formation and combat antimicrobial resistance. AA effectively inhibits biofilm development. Its ability to eradicate mature biofilms is weaker, emphasizing the need for combination therapies or enhanced delivery systems. AA represents a multifunctional, natural antimicrobial candidate with considerable scope for further development to address persistent biofilm-related infections and reduce the global threat of antimicrobial resistance. © 2025 Elsevier B.V.