Régine Janel a, Capucine Braillon a,b, Cendrine Seguin c, Louise Ortet c, Agnès Braud d, Maguy Jaber e, Sylvie Fournel c, Véronique Pitchon f, Sergio Ortiz b, Pierre Fechter a*.

a CNRS, UMR 7242, Biotechnologie et Signalisation Cellulaire, Université de Strasbourg, 67400 Illkirch-Graffenstaden, France ; b UMR 7200 Laboratoire d'Innovation Thérapeutique (LIT), CNRS, Université de Strasbourg, 67400 Illkirch-Graffenstaden, France ; c INSERM UMR_S1121 CNRS EMR7003 Biomaterials and Bioengineering, Université de Strasbourg, Illkirch Cedex, France ; d Université de Strasbourg, CNRS, ENGEES, ICube UMR 7537, F-67000 Strasbourg, France; e Laboratoire d'Archéologie Moléculaire et Structurale (LAMS) UMR 8220, Sorbonne Université UPMC, Paris ; f CNRS, UMR 7044, Archéologie et Histoire Ancienne : Méditerranée- Europe, MISHA, Université de Strasbourg, Strasbourg, France

The rapid emergence of multidrug-resistant bacteria, particularly in the context of biofilm-associated infections, highlights the urgent need for alternative anti-infective strategies beyond conventional antibiotics. In this context, ancient pharmacopoeias represent a largely underexplored reservoir of therapeutic knowledge, built on centuries of empirical observations and combining plant, mineral, and animal-derived ingredients.

 Unlike modern pharmacology, which often focuses on single active compounds, historical preparations frequently rely on complex combinations of ingredients, suggesting complementary or synergistic mechanisms of action. Among these, plant–metal associations appear recurrently in treatments for skin infections, a field in which topical applications allowed the use of otherwise toxic substances such as metals.

 To rationally explore this chemical and biological diversity, we conducted an ethnopharmacological survey of Arabic medical manuscripts dating from the 9th to the 13th century. From more than 300 recorded formulations, 14 preparations targeting infection-related symptoms were identified, of which the majority included metallic components. A preparation described by Al-Kindī1, combining copper with recurrent plant ingredients such as Aloe vera, myrrh and gum ammoniac, was selected based on the frequency and consistency of its components across sources. This selection provided a robust framework to investigate the biological relevance of ancient plant–metal combinations.

[1] Levey, M. (1966). The medical formulary or Aqrābādhīn of al-Kindī. Madison, WI: University of Wisconsin Press.