UPLC-QTof-MS chemical profiling and characterization of antiproliferative and anti-inflammatory compounds from seven Hypericum species in China

• Chemical profiles were established using UPLC-QTof-MS metabolomics . • Over 100 marker compounds contributing to the chemotaxonomy were characterized. • All extracts inhibited NO production in LPS-induced RAW264.7 cells at 100 μ g/mL. • H. japonicum showed cytotoxicity to SMMC-7721 cells (IC 50 = 59.8 μ g/mL). • Potential antiproliferative markers were identified using a chemometrics approach. Many Hypericum species have been used as medicinal plants, herbal teas, and dietary supplements around the world. A previous ethnobotanical survey found that seven Hypericum species in southern China ( H. daliense , H. hengshanense , H. himalaicum , H. japonicum , H. petiolulatum subsp. yunnanense , H. seniawinii , and H. wightianum ) have been used traditionally to treat inflammation and infectious diseases, but studies on the chemical compositions and bioactivities of these folk medicines are limited. The current study aimed to characterize bioactive marker compounds correlated with two in vitro bioassays for cytotoxicity and anti-inflammation. Methanolic extracts of these species were chemically profiled using UPLC-QTof-MS metabolomics, characterizing the 52 major components from these Hypericum species. To chemically differentiate these seven species, 112 chemical features were characterized as potential chemotaxonomic markers, out of which 89 were tentatively identified. Using a chemometric approach, antiproliferative activity was tracked with chemical markers. H. japonicum showed antiproliferative effects on SMMC-7721 human hepatocarcinoma cell line with an IC 50 value of 59.8 μ g/mL. Comparison of H. japonicum to six other Hypericum species revealed that betulinic acid, isojacareubin, and taxifolin are potential antiproliferative compounds. In addition, a primary in vitro anti-inflammatory assay revealed that all the seven extracts inhibited NO production in lipopolysaccharide-induced RAW 264.7 murine macrophage cells at 100 μ g/mL, indicating that anti-inflammatory compounds may exist in all the seven species. Out of the 52 major components identified from these species, 11 have been previously reported to possess anti-inflammatory properties. These findings provide a scientific rationale for traditional uses of the seven Hypericum species in China and merit further study for the development of new medicinal products.