Natural phytochemical-based strategies for antibiofilm applications

Biofilms contribute to the persistence of infectious diseases, complicate the treatment of chronic infections and pose a significant global health threat. However, the effectiveness of antibacterial therapies is often limited by poor penetration of antibiotics, as well as the horizontal transfer of antibiotic resistance genes among bacteria. Phytochemicals remain a promising source for developing novel antibiofilm agents.

A systematic search of literatures was conducted using PubMed, Web of Science, Google scholar, and CNKI, with keywords related to "phytochemicals", "natural products", "natural compounds", "alkaloids", "polyphenols", "terpenoids", "quinones", "nanomaterials", "biofilms", "biofilm formation", "biofilm inhibition", and "structure-activity relationship" focusing on studies published from 2014 to 2025.

A total of 38 most extensively studied natural phytochemicals, including alkaloids, flavonoids (i.e., flavonols, flavanols, and chalcones), quinones, non-flavonoid polyphenols, terpenes and others, were systematically screened based on relevant articles from the past decade. Phytochemicals mainly work by targeting quorum sensing systems, reducing virulence factor production, preventing the initial adhesion and targeting the extracellular polymeric substances of biofilms. Well-designed phytochemical-based nanomaterials can enhance permeability, drug loading efficiency, target drug delivery and sustained drug release of phytochemicals, thereby increasing their antibiofilm efficacy.

Phytochemicals represent a promising therapeutic source for the elimination of bacterial biofilms and associated infections both in the form of molecules or nanomaterials. By synthesizing current progress and identifying future directions, phytochemical-based strategies may inspire innovative solutions and promote translational efforts in combating biofilm-associated challenges in clinical and environmental contexts.