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Chemical evaluation of cimicifugic acids and serotonergic activity of Cimicifuga racemosa roots
In previous receptor binding studies using a comprehensive panel of 5-HT receptor subtypes with a 40% (v/v) isopropanolic, a 75% (v/v) ethanolic, and a methanolic crude extract of C. racemosa roots, the methanolic extract exhibited the highest potency in displacing the ligand from the receptor subtype 7 [1,2]. Subsequent screening studies were therefore conducted with MeOH extracts and screening against the 5-HT7 receptor. The presence of the 5-HT7 receptor subtype in the hypothalamus and the association of the latter with hot flashes in menopausal women provides a rationale for the serotonergic activity-guided evaluation of black cohosh. Using liquid-liquid partitioning, crude root extracts divide into a triterpene (TT) and a phenolic (P) partition. In binding studies the P partition retained all the previously observed 5-HT7 receptor binding activity. The objective of this study was to assess the 5-HT7 receptor binding ability of cimicifugic acids, which are highly abundant in the P partition, of chemotaxonomic value to the genus C., and, therefore, potential marker compounds for extract standardization. A new isolation scheme was developed using a solid phase extraction step for the enrichment of the phenolic compounds, followed by liquid-liquid partitioning using fast centrifugal partition chromatography (FCPC). Employing a pH-zone refinement FCPC method, the cimicifugic acids could first be pooled into one fraction and in a second FCPC step be obtained as pure compounds. Subsequently, cimicifugic acids A, B, E, F and fukinolic acid were studied biologically with respect to their 5-HT7 receptor binding potency, and chemically to their stability in solution by means of qNMR.
Acknowledgement: NIH Grant P50-AT00155, Office of Dietary Supplements (ODS), National Institute of General Medicine (NIGMS), Office for Research on Women's Health (ORWH) and National Center for Complementary and Alternative Medicine (NCCAM).
References: 1. Burdette, J. E. et al. (2003)J. Agric. Food Chem. 51: 5661–5670.
2. Sipe, K. et al. (2004) Brain Res. 1028: 191–202.