{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T09:49:03Z","timestamp":1785750543962,"version":"3.56.0"},"reference-count":89,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Phytomedicines have played a vital role in traditional medical systems globally, particularly in providing culturally relevant and accessible healthcare solutions.\n                      <jats:italic>P. methysticum<\/jats:italic>\n                      , known as Kava, is a traditional Pacific Island phytomedicine with clinically validated anxiolytic properties, primarily attributed to its Kavalactones (KL). However,\n                      <jats:italic>P. methysticum<\/jats:italic>\n                      is biogeographically restricted and there are ecological and cultural concerns that limits its widespread therapeutic adoption. This study investigates if other\n                      <jats:italic>Piper<\/jats:italic>\n                      species, used phytomedically outside the Pacific, offer therapeutic efficacy for anxiety, stress, and related disorders as alternatives to Kava. We used a hybrid computational and experimental validation approach.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A new data platform aggregating non-Western phytomedical pharmacopeias was used to analyze the secondary metabolomes of various\n                      <jats:italic>Piper<\/jats:italic>\n                      species. Network analysis and multidimensional data projections compared chemical composition and therapeutic indications of these species with those of\n                      <jats:italic>P. methysticum<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our findings suggest that while Kavalactones are predominantly unique to\n                      <jats:italic>P. methysticum<\/jats:italic>\n                      , other\n                      <jats:italic>Piper<\/jats:italic>\n                      species also contain bioactive compounds associated with anxiolytic and stress-relieving effects, a subset of which were validated in an\n                      <jats:italic>in vivo<\/jats:italic>\n                      model pilot study.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings identify new potential avenues for exploration of phytomedical solutions to complex interconnected sleep, pain, stress, movement and anxiety issues that hallmark disorders such as PTSD and Parkinson\u2019s.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1750146","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T09:29:15Z","timestamp":1785749355000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational analysis of therapeutic potential for simplified Piper spp.- derived medicinal mixtures in anxiety, sleep, pain and seizure"],"prefix":"10.3389","volume":"17","author":[{"given":"B. 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