Microbiota-mediated biotransformation of triterpene glycosides from Cimicifuga racemosa extract Ze 450

The pharmacological efficacy of Cimicifuga racemosa extract Ze 450 in treating menopausal symptoms is thought to be linked to triterpene glycosides (TTGs) [ 1 ] [ 2 ]. Emerging evidence suggests that intestinal microbiota may metabolize TTGs into bioactive aglycones, potentially contributing to the extract’s therapeutic effects [ 3 ]. This study investigated the biotransformation of selected TTGs (23-epi-26-deoxyactein, actein, cimigenol-3-β-D-xyloside, and cimigenol-3-α-L-arabinoside) using ex vivo incubation with human stool samples (n=8) under strict anaerobic conditions for 48 hours [ 4 ]. Qualitative analysis was performed using UHPLC-qTOF-MS, revealing complete degradation of all investigated TTGs after incubation. Quantitative analysis of the biotransformation of deoxyactein showed a significant increase in its aglycone, which varied among donors, indicating individual differences in microbial activity and metabolic capacity. Stability of deoxyactein over gastrointestinal phases was proven by using simulated fluids across the oral and gastric phases. These findings confirm a microbiota-mediated cleavage of the glycosidic moieties, yielding potentially active aglycones. Effects of TTGs and Ze 450 on microbial community were studied using alpha and beta diversity metrics, along with modulation of short-chain fatty acids (SCFAs). No significant adverse effects on microbial community structure or SCFA profiles were observed, though minor shifts in taxonomic profiles (Bray-Curtis distance) were noted for select donors. This proof-of-concept study highlights the importance of individual microbiome variability in TTG metabolism and lays the foundation for personalized phytotherapeutic strategies. Ongoing work aims to correlate microbiome taxonomy with metabolic conversion efficiency to enhance therapeutic consistency and optimize the clinical efficacy of Ze 450. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany