Cimicifuga racemosa extract targets mitochondrial metabolism by suppressing TCA-cycle dependent substrate utilization

Introduction Cimicifuga racemosa extract exerts a number of potential clinical benefits – most of them related to womens’ health and the relief of menopausal complaints. The decline in estrogen levels during menopause and ageing affects the metabolism, resulting e.g., in weight gain and increasing cardiovascular risks, but also in central nervous system-related disorders. Mitochondria play important roles in several aspects of these age-related processes, through regulation of ATP production, calcium homeostasis, metabolism and apoptosis. In addition, reactive oxygen species (ROS) generated by mitochondria as byproducts of oxidative phosphorylation may significantly contribute to metabolic dysfunctions and senescence.

However, it is still unknown how the Cimicifuga racemosa extract Ze 450 affects mitochondrial signaling and whether this serves as a key mechanism for the established therapeutic effects of Ze 450 against menopausal symptoms.

Aim The aim of the present study was to investigate mechanisms by which the Cimicifuga extract Ze 450 regulates mitochondrial metabolism and function under physiological conditions and in the context of menopause and age-related (metabolic) diseases.

Method To gain a comprehensive insight into the signaling effects of the extract on the mitochondrial proteome, neuronal HT22 cells were treated with Ze 450 and analyzed by mass spectrometry. Simultaneous measurement of mitochondrial and glycolytic respiration also detected acute effects of the Cimicifuga extract on the mitochondrial energy turnover. MitoPlates™ were used to understand how substrate utilization and metabolic activity are reprogrammed upon treatment.

Results Ze 450 extract exerts strong effects on mitochondrial metabolism by reducing substrate utilisation, especially of glutamine and glucose in the TCA cycle. This led to a reduced activity of the electron transport chain. As a positive effect neuronal cells were more resistant against oxidative stress.

Conclusion These results provide evidence that Ze 450 has beneficial effects on mitochondria, which could be a promising therapeutic target for the prevention of menopause and age-related neurodegenerative processes and metabolic disorders.

Publication History

Article published online:
13 June 2022