Ammi majus, a well-established member of the Umbelliferae (Apiaceae) family, is endogenous to Egypt. The main parts of this plant that are used are the fruits, which contain coumarins and flavonoids as major active constituents. The roots are usually considered by-products that are discarded and not fed to cattle because of coumarins' potential toxicity. The goal of this study was to ensure the sustainability of the plant, investigate the active metabolites present in the roots using UPLC/MS-MS, isolate and elucidate the major coumarin Xanthotoxin, and predict its oral bioavailability and its potential biological impact on tongue papillae. The results revealed coumarins as the dominant chemical class in a positive acquisition mode, with bergaptol-O-hexoside 5%, Xanthotoxin 5.5%, and isoarnoittinin 6% being the major compounds. However, phenolics ruled in the negative mode, with p-coumaroyl tartaric acid 7%, 3,7-dimethyl quercetin 6%, and hesperidin 5% being the most prominent metabolites. Fractionation and purification of the chloroform fraction yielded Xanthotoxin as one of the main compounds, which appeared as white needle crystals (20 mg). ADME studies for oral bioavailability were performed to predict the potential properties of the compound if used orally. It was noted that it followed Lipinski's rule of five, had just one parameter outside of the pink area in the radar plot, and was detected inside the threshold area using the boiled egg approach. In vivo, histopathological studies performed on rats showed a notable decrease in the tongue's keratin thickness from an average of 51.1 µm to 9.1 µm and an average of 51.8 µm to 9.8 µm in fungiform and filiform cells, respectively. The results indicated that although Xanthotoxin is a well-known medical agent with several potential therapeutic activities in oral therapy, it may cause a destructive effect on the structure of the specialized mucosa of the tongue.
Keywords: ADME; Ammi majus roots; Apiaceae; Xanthotoxin; boiled egg; health care; histopathological studies; metabolites; oral safety.