Planta Med 2007; 73 - P_456
DOI: 10.1055/s-2007-987236

Aged Garlic Extract Enhances Endothelial Nitric Oxide Release via Increased Tetrahydrobiopterin Bioavailability

L Papatheodorou 1, N Morihara 1, N Ide 1, P Koelle 1, N Weiss 1
  • 1Medizinische Poliklinik Innenstadt, Klinikum der Universität München, Pettenkoferstr. 8a, D-80336München, Germany

Introduction: Aged garlic extract (AGE) has been shown to enhance endothelial nitric oxide (NO) production in mice [1] and to restore endothelial dysfunction due to impaired NO bioavailability in humans with acutely elevated homocysteine (hcy) levels [2]. As reduced NO bioavailability during elevated hcy seems to be due to reduction of the NO synthase cofactor tetrahydrobiopterin (BH4) leading to „uncoupling“ of the enyzme [3] we hypothesized that AGE may preserve endothelial BH4 levels via its antioxidant and thiol-modifying properties, thereby increasing NO release. Methods: Human endothelial cells (EA.hy 926) were incubated for 24h with hypoxanthine, aminopterin, thymidine and methionine (HAT/MET) to increase cellular hcy levels, and with and without AGE (5mg/mL). Cellular levels of hcy, BH4, glutathione, and total thiols were measured by HPLC, and endothelial NO production using the fluorescent probe DAF-2. Results: Incubation of endothelial cells with HAT/MET resulted in a significant 2-fold increase in cellular hcy levels (from 0.17±0.03 to 0.35±0.08µmol/mg), coincubation with AGE had no significant effect on hcy in both control and HAT/MET treated cells. Elevated cellular hcy went along with significantly decreased levels of BH4 (2.23±0.28 vs. 4.34±0.64pmol/mg). Incubation with AGE slightly increased BH4 in control cells (5.33±0.65pmol/mg), and prevented the decline in BH4 in HAT/MET treated cells (5.23±0.71pmol/mg). AGE increased cellular levels of total thiols and glutathione, and prevented HAT/MET induced decrease in endothelial NO release. Conclusions: AGE maintains NO bioavailability in endothelial cells even under conditions of elevated hcy levels via increasing cellular BH4 levels, thereby maintaining normal endothelial function. This may contribute to AGE's antiatherosclerotic properties.

Acknowledgement: Supported by Wakunaga of America, Mission Viejo, CA., USA.

References: [1] Morihara N. et al. (2002) Life Sci 71: 509 [2] Weiss N. et al. (2006) J Nutr 136: 750S [3] Topal G et al. (2004) Free Radic Biol Med. 36: 1532.