Abstract
The tormentil rhizome (Potentilla erecta L.) is traditionally used to treat gastrointestinal and inflammatory disorders, yet the mechanisms underlying its immunomodulatory activity remain unclear. No studies have examined the metabolism of tormentil constituents by the human gut microbiota and their effects on innate immune cells. This study evaluated the effects of the ethanolic extract of tormentil rhizome (EtTR) and its gut microbiota-derived metabolites (TRGMs) on innate immune function using human neutrophils and THP-1-derived macrophages. The chemical composition of EtTR and TRGMs was characterized by LC-MS, revealing fractions enriched in catechins and procyanidins (30% MeOH) or ellagic acid derivatives and triterpenes (100% MeOH). EtTR and all TRGM fractions significantly reduced ROS production, while the extract and selected metabolites decreased IL-1β and TNF-α secretion in neutrophils, whereas IL-8 showed marked induction. In macrophages, EtTR and selected fractions suppressed TNF-α and MCP-1 release but variably affected IL-6, reflecting donor-dependent modulation. The strongest inhibition was observed for fractions rich in catechins and triterpenoid conjugates, indicating synergistic activity between these compound classes. Overall, EtTR and its microbiota-derived metabolites exerted complementary antioxidant and immunomodulatory effects, providing mechanistic evidence that microbial transformation of tormentil polyphenols yields bioactive postbiotic metabolites capable of modulating inflammatory signaling.