The Identification and Characterization of the Cardioactive Principals in Hawthorn Extract

by Niel HenriksenMentor: Dr. Phil Proteau College of Pharmacy

Hawthorn and Heart Failure

• Congestive heart failure (CHF) results from coronary artery disease, a previous heart attack, high blood pressure, heart defects, and infections in the heart tissue.

• Nearly 5 million people in the United States are diagnosed with CHF.

• The symptoms of CHF include shortness of breath, fatigue, swelling and kidney dysfunction.

Hawthorn Extract Benefits

• Clinical trials by the NYHA demonstrated: (+) exercise tolerance

(-) dyspnea (shortness of breath)(-) ankle swelling(-) blood pressure

• Studies on cardiac tissue show: (+) inotropic effects

(+) cardiac flux (+) vasorelaxation(+) anti-arrhythmic potential

Hawthorn Extract Unknowns

• Active compound(s)– Flavonoids and Procyanidins?

• Mechanism of action

• Proper dosing

• Duration of therapy

• Most effective extract source (berries, leaves, or flowers)

Project Goals

• Develop cell based bioassays for evaluation of the direct cardiac effects of hawthorn extract

• Using bioassay-guided fractionation, identify the components in hawthorn extract with cardiac activity

Bioassay Tests

• Rate of Contraction

• Amplitude of Contraction

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Isolation Techniques

• Solvent Extraction

• Thin-Layer Chromatography

• Large Scale Chromatography

• High Performance Liquid Chromatography

Identification Techniques

• Mass Spectrometry

• Nuclear Magnetic Resonance (NMR) Spectroscopy

Future Goals

• Complete bioassay-guided fractionation

• Determine the most effective extract source

• Determine the mechanism through with hawthorn extract functions

• Correlate the plasma levels of cardioactive component with the physiologic effects on animal models

Acknowledgements

• Dr. Phil Proteau

• Shannon Long

• Dr. Theresa Filtz

• Dr. Kevin Ahern

• Howard Hughes Medical Institute