# Pilot Investigation on the Metabolic Effects of Cimicifuga racemosa Extract Ze 450 and Voluntary Physical Activity in Female Rats

**Authors:** Elisabeth Habersatter, Tihomir Kostov, Nele Laing, Jürgen Drewe, Georg Boonen, Veronika Butterweck, Patrick Rene Diel

PMC · DOI: 10.3390/ijms27020977 · International Journal of Molecular Sciences · 2026-01-19

## TL;DR

This study explores how a plant extract and exercise affect metabolism and fat in female rats, finding both reduce fat without harming the liver.

## Contribution

The study is the first to show that Cimicifuga racemosa extract Ze 450 and voluntary exercise share metabolic benefits in reducing visceral fat and leptin.

## Key findings

- Ze 450 and voluntary running reduced visceral fat mass and adipocyte size.
- Both interventions lowered serum leptin levels, suggesting shared metabolic mechanisms.
- Running reduced serum cholesterol, while Ze 450 had no effect on liver enzymes or weight.

## Abstract

Cimicifuga racemosa extracts, particularly the ethanolic extract Ze 450, are widely used to alleviate menopausal symptoms, such as hot flushes and excessive sweating. While their clinical efficacy is well established, the effects of these interventions on systemic energy metabolism remain unclear. This pilot study investigated the impact of Ze 450 on body composition, metabolic markers, and voluntary physical activity in non-ovariectomized female Wistar rats. Animals (N = 36) received Ze 450 at either 30 mg/kg or 130 mg/kg body weight, with or without access to voluntary wheel running over four weeks. Neither treatment influenced body weight gain or final body weight, indicating normal growth across all groups. Post-mortem analyses included visceral fat mass, serum cholesterol, and leptin levels. Both Ze 450 and running reduced visceral fat mass, adipocyte size, and circulating leptin levels, suggesting that they share overlapping mechanisms. Serum cholesterol was significantly lowered by running but remained unaffected by Ze 450, while liver weight and alanine aminotransferase activity were unchanged, confirming hepatic safety. Collectively, Ze 450 improved key metabolic parameters related to adiposity and appetite without affecting hepatic integrity, highlighting its potential as a safe, non-hormonal metabolic modulator complementary to physical activity.

## Linked entities

- **Chemicals:** leptin (PubChem CID 157010069), alanine aminotransferase (PubChem CID 251717)

## Full-text entities

- **Genes:** Lep (leptin) [NCBI Gene 25608] {aka OB, obese}
- **Diseases:** adiposity (MESH:D018205), weight gain (MESH:D015430), hot flushes (MESH:D005483)
- **Chemicals:** cholesterol (MESH:D002784), extract (-)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12842429/full.md

## References

34 references — full list in the complete paper: https://tomesphere.com/paper/PMC12842429/full.md

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Source: https://tomesphere.com/paper/PMC12842429