Fissistigma polyanthum is a renowned medicinal plant traditionally used by over 10 ethnic groups in China to treat various ailments, including inflammation. However, research on its chemical composition and bioactivity remains limited. This study investigated the chemical profiles and biological activities across different parts of F. polyanthum, aiming to identify the bioactive molecules associated with anti-inflammatory and anti-Alzheimer's effects. To ensure accurate metabolite identification, an in-house Fissistigma compound library containing 654 chemicals was constructed and integrated with the Progenesis QI informatics platform. Using UPLC-ESI-QTOF-MS-based metabolomics, 97 compounds, including alkaloids, flavonoids and terpenoids, were identified, of which 86 were reported for the first time in this species. Heatmap analysis revealed significant content variations of these constituents across different plant parts: leaves were rich in flavonoids and terpenoids, while the root without bark was abundant in alkaloids. PCA and PLS-DA analyses confirmed significant metabolite differences among the plant parts, with 31 key differential compounds explaining the chemical variations. Comparative bioactivity assays showed that the root without bark exhibited strong anti-butyrylcholinesterase activity, with an IC50 value of 54.22 μg/mL, while the root bark and leaves demonstrated the strongest inhibition of NO production, with IC50 values of 62.64 and 71.85 μg/mL, respectively. The S-plot analysis further identified 25 potential bioactive compounds, primarily alkaloids and flavonoids, responsible for the observed bioactivities, including known anti-inflammatory and anti-Alzheimer's agents. These findings underscore the pharmaceutical potential of F. polyanthum and the effectiveness of integrating metabolomics and chemometrics to discover bioactive molecules in medicinal plants.
