Antibacterial activity of caffeic acid from plant sources: A review based on in silico, in vitro and in vivo approaches

Caffeic acid (CFFA) is a ubiquitously available and naturally procured polyphenol with enormous importance due to its broad-spectrum biological activities. It is the yellow solid 3,4- hydroxycinnamic acid and obeys Lipinski’s rule of five with zero violation. This review paper aims to investigate various perspectives regarding the antibacterial activities of CFFA. An extensive literature review considered a time range of 1990-2025 and utilized multiple keywords. Some of those keywords included- caffeic acid, caffeic acid pharmacological aspects, caffeic acid biosynthesis/synthesis, the antibacterial activity of caffeic acid, and plant sources of caffeic acid. Further compilation, analysis, and preparation for this review were accomplished based on the information obtained from search queries. It is found that CFFA plays antibacterial roles against a wide range of pathogens, both gram-positive ( Staphylococcus aureus , Streptococcus pneumoniae, Enterococcus faecalis ) and gram-negative ( Escherichia coli , Klebsiella pneumoniae , and Pseudomonas aeruginosa ). This review also elaborates on the plant-specific sources, chemistry, biosynthesis, and pharmacokinetics of CFFA. The immune-modulatory perspectives on bacterial infection prevention have been discussed. The in vitro, in vivo , and in silico approaches regarding various investigations with CFFA and its anti-infective roles have been explained. The combinational antibacterial activities of CFFA with multiple antibiotics and other phytochemicals have been discussed. The anti-biofilm, anti-quorum sensing, cell wall synthesis inhibition, and anti-efflux pump mechanisms of CFFA action were elaborated. CFFA bears an excellent pharmacological profile and enormous antibacterial actions. Despite some limitations of this compound regarding its solubility or bioavailability, this molecule may be used as a naturally procured effective antibacterial compound. Overall, CFFA displays broad-spectrum antimicrobial activities demonstrating different mechanisms of action with favorable pharmacological properties. However, further research is mandatory to validate CFFA as a novel therapeutic agent to combat bacterial infections.