The Identification and Characterization of the Cardioactive Principals in Hawthorn Extract by Niel Henriksen Mentor: 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

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