TCM-derived natural photosensitizers offer a novel integrative approach to combat bacterial, viral, and fungal infectionsNatural Photosensitizers Show Potential Against Bacterial and Viral Infections

Photodynamic therapy (PDT) has emerged as a promising non-antibiotic strategy for combating pathogenic infections through the generation of reactive oxygen species (ROS) from a light-activated photosensitizer (PS), which interrupts microbial structures and functions. Natural products such as coumarin, curcumin, riboflavin, pheophorbide a, and hypericin have long been studied as PSs that have the functions of intrinsic antimicrobial, antiviral, antifungal, and antiparasitic activities. These metabolites are broadly distributed across multiple ethnomedical traditions worldwide, with a focus on those explicitly documented in the Chinese Pharmacopoeia and widely applied in Traditional Chinese Medicine (TCM), while acknowledging their broader global distribution. Natural PSs have some limitations for PDT efficacy. Recent advances in nanotechnology and drug delivery systems have enabled the development of TCM-derived advanced PSs with improved solubility, bioavailability, and targeted accumulation at infection sites. This narrative review was conducted through a comprehensive search of multiple electronic databases, including PubMed, ScienceDirect, Scopus, Web of Science, and the China National Knowledge Infrastructure (CNKI). The search encompassed literature published over the past three decades, without restrictions on language. Studies were considered eligible if they contained the keywords “Photodynamic Therapy”, “Pathogenic infection”, “Coumarin”, “Curcumin”, “Riboflavin”, “Pheophorbide a”, and “Hypericin”. Duplicate records were excluded during screening. All relevant publications were collected, critically appraised, and synthesized to provide mechanistic insights, preclinical evidence, and translational perspectives on the application of TCM–derived PSs in photodynamic therapy against bacterial biofilms, viral pathogens, and fungal infections. The synergistic benefits include overcoming antimicrobial resistance, enhancing host immune responses, and reducing reliance on conventional antibiotics. Challenges remain in optimizing pharmacokinetics, minimizing off-target toxicity, and advancing clinical validation or translation. Thus, TCM-derived advanced PS represent a novel and integrative approach to fight against pathogenic infection, bridging ethnopharmacology with modern photomedicine, and hold significant potential or advantages for clinical application in the future.