Validation of a 16th Century Traditional Chinese Medicine Use of Ginkgo biloba as a Topical Antimicrobial

In the search for new therapeutic solutions to address an increasing number of multidrug-resistant bacterial pathogens, secondary metabolites from plants have proven to be a rich source of antimicrobial compounds. Ginkgo biloba, a tree native to China, has been spread around the world as an ornamental tree. Its seeds have been used as snacks and medical materials in Traditional Chinese Medicine (TCM), while over the last century its leaf extracts emerged as a source of rising pharmaceutical commerce related to brain health in Western medicine. Besides studies on the neuro-protective effects of Ginkgo, its antibacterial activities have gained more attention from researchers in the past decades, though its leaves were the main focus. We reviewed a 16th-century Chinese text, the Ben Cao Gang Mu by Li Shi-Zhen, to investigate the ancient prescription of Ginkgo seeds for skin infections. We performed antibacterial assays on various Ginkgo seed extracts against pathogens (Staphylococcus aureus, Cutibacterium acnes, Klebsiella pneumoniae, Acinetobacter baumannii, Streptococcus pyogenes) relevant to skin and soft tissue infections (SSTIs). We demonstrate here that Ginkgo seed coats and immature seeds exhibit antibacterial activity against Gram-positive skin pathogens (C. acnes, S. aureus, and S. pyogenes), and thus validated its use in TCM. We also identified one compound tied to the antibacterial activity observed, ginkgolic acid C15:1, and examine its toxicity to human keratinocytes. These results highlight the relevance of ancient medical texts as leads for the discovery of natural products with antimicrobial activities.