Gastrointestinal Stability and Microbiota-Mediated Deglycosylation of Triterpene Glycosides from Cimicifuga racemosa Extract Ze 450

Triterpene glycosides (TTGs) are characteristic constituents of Cimicifuga racemosa extract Ze 450 and may contribute to its pharmacological effects in the treatment of menopausal symptoms. This exploratory study investigated their gastrointestinal stability, transformation during incubation with human fecal microbiota, and potential effects on microbial community composition and short-chain fatty acid (SCFA) production. The stability of 23-epi-26-deoxyactein was assessed during simulated oral and gastric digestion using the INFOGEST protocol. Microbiota-associated biotransformation of actein, 23-epi-26-deoxyactein, cimigenol-3-β-D-xyloside, and cimigenol-3-α-L-arabinoside was subsequently examined during 48 h anaerobic ex vivo cultivation with fecal microbiota from eight female donors. 23-Epi-26-deoxyactein remained largely stable during simulated oral and gastric digestion. During fecal incubation, all investigated TTGs were depleted and the corresponding aglycones were detected. Quantification of the 23-epi-26-deoxyactein aglycone revealed marked donor-dependent differences, indicating substantial interindividual variability in TTG biotransformation. Individual TTGs had little effect on microbial community composition or SCFA profiles, whereas Ze 450 induced a small but significant shift in overall community structure without substantially affecting SCFA production. These findings demonstrate extensive microbiota-mediated TTG deglycosylation and highlight marked interindividual variability in TTG metabolism, providing a rationale for further investigation of microbiome-dependent differences in the pharmacological fate of Ze 450.