Planta Med 2008; 74 - SL115
DOI: 10.1055/s-0028-1083995

Chemical evaluation of cimicifugic acids and serotonergic activity of Cimicifuga racemosa roots

T Goedecke 1, D Nikolic 1, DC Lankin 1, SL Powell 1, JL Bolton 1, RV van Breemen 1, GF Pauli 1
  • 1UIC/NIH Center for Botanical Dietary Supplements Research, Department of Medicinal Chemistry and Pharmacognosy (MC 781) and PCRPS, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood St., Chicago, IL, 60612, USA

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.