AMPK Activation by Cimicifuga racemosa Extract Ze 450 Is Associated with Metabolic Effects and Cellular Resilience against Age-Related Pathologies in Different Tissue Cell Types
Cimicifuga racemosa extracts (CREs) have gained well-established use for the treatment of menopausal symptoms such as hot flushes and excessive sweating, and weight gain. While the clinical effects of CREs have been well documented, the mechanisms underlying these effects are largely unknown. Mor...
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Main Authors: | , , , , , , , , |
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Format: | Article |
Language: | English |
Published: |
Philipps-Universität Marburg
2024
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Subjects: | |
Online Access: | PDF Full Text |
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Summary: | Cimicifuga racemosa extracts (CREs) have gained well-established use for the treatment of
menopausal symptoms such as hot flushes and excessive sweating, and weight gain. While the clinical
effects of CREs have been well documented, the mechanisms underlying these effects are largely
unknown. More recently, the metabolic effects of the CRE Ze 450 were demonstrated in cultured cells
in vitro and in mouse models of obesity in vivo. At the molecular level, metabolic regulation, enhanced
insulin sensitivity, and increased glucose uptake were linked to the activation of AMP-activated protein
kinase (AMPK). Therefore, we tested the effects of Ze 450 on AMPK phosphorylation and thus activation
in cells from different tissues, i.e., murine C2C12 myoblast cells, human HEPG2 liver cells, mouse HT22
neuronal cells, and in murine 3T3L1 adipocytes. Using a FRET-based HTRF-assay, we found that Ze
450 induced AMPK phosphorylation and the activation of this key enzyme of metabolic regulation
in cells from various different tissues including C2C12 (muscle), HEPG2 (liver), HT22 (hippocampal),
and 3T3-L1 (adipocyte) cells. In C2C12 muscle cells, enhanced AMPK activation was accompanied
by reduced mitochondrial respiration and enhanced glucose uptake. Further, Ze 450 enhanced the
resilience of the cells against oxidative death induced by ferroptosis inducers erastin or RSL3. Our
findings suggest a general effect of Cimicifuga racemosa on AMPK activation in different tissues and
across species. This may have a significant impact on expanded therapeutic applications of Ze 450, since
AMPK activation and the related metabolic effects have been previously associated with anti-aging
effects and the prevention of the metabolic syndrome. |
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Item Description: | Gefördert durch den Open-Access-Publikationsfonds der UB Marburg. |
Physical Description: | 16 Pages |
DOI: | 10.3390/pharmaceutics16030393 |