In vitro human fecal microbial metabolism of Forsythoside A and biological activities of its metabolites.

The present study aimed to investigate the metabolism of Forsythoside A (FTA) by human fecal bacteria to clarify the relationship between its intestinal metabolism and its pharmacological activities. FTA was incubated with human fecal microflora in vitro to investigate its metabolic process, and highly sensitive and specific ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed using MetaboLynx software for metabolite analysis. Caffeic acid (CA) and hydroxytyrosol (HT) were obtained by hydrolysis of FTA, and CA was further hydrogenated to form 3,4-dihydroxybenzenepropionic acid (DCA). The anticomplementary, antimicrobial and antiendotoxin activities of FTA and its metabolites by human fecal microflora were evaluated in vitro with a hemolysis assay, the agar disc-diffusion method, the MIC value and the gel clot LAL assay, respectively. The metabolites showed higher biological activity than FTA, especially HT and DCA. Orally administered FTA may be metabolized to HT and DCA, and the pharmacological effects of FTA may be dependent on intestinal bacterial metabolism.