Computational analysis of therapeutic potential for simplified Piper. spp- derived medicinal mixtures in anxiety, sleep, pain and seizure

Abstract Phytomedicines have played a vital role in traditional medical systems globally, particularly in providing culturally relevant and accessible healthcare solutions. Piper methysticum , known as Kava, is a traditional Pacific Island phytomedicine with clinically validated anxiolytic properties, primarily attributed to its Kavalactones. However, the biogeographically restricted distribution of Piper methysticum and the ecological and cultural concerns surrounding its widespread adoption highlight the need to explore alternative sources within the Piper genus. This study investigates whether other species within the Piper genus, used phytomedically in non-Pacific contexts, exhibit similar therapeutic efficacy for anxiety, stress, and related disorders including Post-Traumatic Stress Disorder (PTSD). We employed a computational approach utilizing a novel data platform of non-Western phytomedical pharmacopeias to analyze the secondary metabolomes of various Piper species. Network analysis and multidimensional data projections were used to compare the chemical composition and therapeutic indications of these species with those of Piper methysticum . Our findings suggest that while Kavalactones are predominantly unique to Piper methysticum , other Piper species also contain bioactive compounds associated with anxiolytic and stress-relieving effects. These results provide insight into the potential for culturally and biogeographically contextualized approaches to PTSD treatment, beyond the exclusive use of Kava, and lay the groundwork for future research into alternative phytomedicinal therapies within the Piper genus.