24 - Computational Biochemistry and Classical Texts: Modeling the Pharmacodynamics of Iris in Ancient Lung and Respiratory Therapies

Presenters

Kurt Werner, Wesleyan University; Andrea Roberts, Wesleyan University; and Kate Birney, Wesleyan University

Abstract

For centuries, ancient physicians and authors documented the numerous medicinal uses of the iris rhizome (I. pallida or I. germanica)—treatments that were applied to conditions from liver inflammation (Gal., De loc. aff. 11.793K) to hearing loss (Celsus, Med. 6.7B), uterine pain (Hippoc., Mul. 2.52), constipation (Theophr., De odoribus 8.36), or ulcerous sores and flatulence (Plin., HN 11.83.140–142). Among its many applications, iris is prevalent as a treatment for lung ailments and respiratory symptoms. Although the specific biomechanisms remain unknown, the classical (and later) emphasis on the use of iris for softening hard tissues, thinning fluids, and reducing tumors and warts may point toward specific bioactive roles or pathways in a variety of respiratory illnesses and cancers. This project presents the phytochemical characterization of rhizomes of two I. pallida varietals from Umbria, Italy, and Connecticut, USA, and identifies key flavonoids with bioactive potential. It then analyzes descriptions of iris use in classical texts alongside biomechanisms of iris lung therapies, and employs modern biochemical and computational modeling techniques to identify potential binding to key targets in lung diseases, with a particular focus on the predominant flavonoid irigenin. Specific targets include fibronectin in nonsmall cell lung cancer, and mitogen-activated protein kinases (MAPKs) in respiratory inflammation and carcinoma. Irigenin is computationally evaluated with these protein targets using predictive and modeling software like AutoDock, LigPlot+, PyMOL, and Swiss-Model. Phytochemical overlap between the geographic variants of I. pallida highlights common biomarkers useful for the identification of archaeological organic residues. Blending biochemistry with detailed study of Greek and Latin texts offers a new vehicle by which to understand the mechanisms of ancient drugs, or even to identify new candidates for modern drug design in classical sources.