Ginkgo biloba Extract Improves Coronary Blood Flow in Patients with Coronary Artery Disease: Role of Endothelium-Dependent Vasodilation

Abstract

Ginkgo biloba extract (GBE) has well-documented cardioprotective effects on coronary flow and positive effects on vasodilation through endothelium-derived nitric oxide in experimental animals, but these impacts in patients with coronary artery disease (CAD) have not yet been investigated. We designed this study to test the effects of GBE on distal left anterior descending coronary artery (LAD) blood flow and endothelium-dependent brachial artery flow-mediated dilation (FMD) in patients with CAD. Eighty CAD patients were randomly assigned to either GBE or saline (control) groups. LAD blood flow and brachial artery FMD were measured non-invasively using high-resolution ultrasound before and after intravenous administration of GBE or saline. GBE significantly increased LAD blood flow in maximal diastolic peak velocity (MDPV), maximal systolic peak velocity (MSPV) and diastolic time velocity integral (DTVI) compared with the control group (16.14 ± 10.93 % vs. 0.28 ± 2.14 %, 9.14 ± 8.23 % vs. 0.79 ± 2.56 %, and 15.23 ± 7.28 % vs. 0.42 ± 2.43 %, respectively, p < 0.01). Brachial artery FMD was also increased by 69.75 % (from 3.95 ± 1.49 % to 6.55 ± 2.51 %, p < 0.01). A linear correlation was found between the percentage changes in MDPV, MSPV, or DTVI of LAD blood flow and the percentage change in brachial artery FMD following treatment with GBE (r = 0.612, 0.486, or 0.521, respectively, p < 0.01). In summary, our data demonstrate that GBE treatment in CAD patients leads to an increase of LAD blood flow in MDPV, MSPV and DTVI, and the increase response might relate to the improved endothelium-dependent vasodilatory capacity.

Abbreviations

CAD: coronary artery disease

DTVI: diastolic time velocity integral

FMD: flow-mediated dilation

GBE: Ginkgo biloba extract

LAD: distal left anterior descending coronary artery

MDPV: maximal diastolic peak velocity

MSPV: maximal systolic peak velocity

NO: nitric oxide

TTDE: transthoracic Doppler echocardiography

Key words

Ginkgo biloba - Ginkgoaceae - coronary artery disease - endothelial function - flow-mediated dilation - transthoracic Doppler echocardiography

References

• 1 Dubey A K, Shankar P R, Upadhyaya D, Deshpande V Y. Ginkgo biloba-an appraisal.  Kathmandu Univ Med J. 2004;  2 225-9.
• 2 Zhang C Q, Zu J, Shi H M, Liu J Y, Qin C Y. The effect of Ginkgo biloba extract (EGb 761) on hepatic sinusoidal endothelial cells and hepatic microcirculation in CCl4 rats.  Am J Chin Med. 2004;  32 21-31.
• 3 Rioufol G, Pietri S, Culcasi M, Loufoua J, Staat P, Pop C. et al . Ginkgo biloba extract EGb 761 attenuates myocardial stunning in the pig heart.  Basic Res Cardiol. 2003;  98 59-68.
• 4 Varga E. The protective effect of EGb 761 in isolated isochemical/reperfused rat hearts.  Acta Pharm Hung. 2002;  72 265-71.
• 5 Zhu G Y, Zhu X L, Geng Q X, Zhang X, Shao J. Change of peripheral blood monocytes derived macrophage scavenger receptors activity in patients with coronary heart disease, and the intervention effect of Ginkgo biloba extract.  Zhongguo Zhong Xi Yi Jie He Za Zhi. 2004;  24 1069-72.
• 6 Deng Y K, Wei F, An B Q. Effects of ginaton on the markers of myocardial injury during cardiopulmonary bypass.  Zhongguo Zhong Xi Yi Jie He Za Zhi. 2006;  26 316-8.
• 7 Halcox J P, Schenke W H, Zalos G, Mincemoyer R, Prasad A, Waclawiw M A. et al . Prognostic value of coronary vascular endothelial dysfunction.  Circulation. 2002;  106 653-8.
• 8 Chen X, Salwinski S, Lee T J. Extracts of Ginkgo biloba and ginsenosides exert cerebral vasorelaxation via a nitric oxide pathway.  Clin Exp Pharmacol Physiol. 1997;  24 958-9.
• 9 Delaflotte S, Auguet M, DeFeudis F V, Baranes J, Clostre F, Drieu K. et al . Endothelium-dependent relaxations of rabbit isolated aorta produced by carbachol and by Ginkgo biloba extract.  Biomed Biochim Acta. 1984;  43 S212-6.
• 10 Kubota Y, Tanaka N, Kagota S, Nakamura K, Kunitomo M, Umegaki K. et al . Effects of Ginkgo biloba extract feeding on salt-induced hypertensive Dahl rats.  Biol Pharm Bull. 2006;  29 266-9.
• 11 Liebgott T, Miollan M, Berchadsky Y, Drieu K, Culcasi M, Pietri S. Complementary cardioprotective effects of flavonoid metabolites and terpenoid constituents of Ginkgo biloba extract (EGb 761) during ischemia and reperfusion.  Basic Res Cardiol. 2000;  95 368-77.
• 12 Chatterjee S S, Gabard B. Studies on mechanism of action of an extract of Ginkgo biloba, a drug used for treatment of ischemic vascular diseases.  Naunyn Schmiedebergs Arch Pharmacol. 1982;  321 207.
• 13 Daimon M, Watanabe H, Yamagishi H, Kuwabara Y, Hasegawa R, Toyoda T. et al . Physiologic assessment of coronary artery stenosis without stress tests: noninvasive analysis of phasic flow characteristics by transthoracic Doppler echocardiography.  J Am Soc Echocardiogr. 2005;  18 949-55.
• 14 Celermajer D S, Sorensen K E, Gooch V M, Spiegelhalter D J, Miller O I, Sullivan I D. et al . Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis.  Lancet. 1992;  340 1111-5.
• 15 Matsuo S, Matsumoto T, Takashima H, Ohira N, Yamane T, Yasuda Y. et al . The relationship between flow-mediated brachial artery vasodilation and coronary vasomotor responses to bradykinin: comparison with those to acetylcholine.  J Cardiovasc Pharmacol. 2004;  44 164-70.
• 16 Teragawa H, Ueda K, Matsuda K, Kimura M, Higashi Y, Oshima T. et al . Relationship between endothelial function in the coronary and brachial arteries.  Clin Cardiol. 2005;  28 460-6.
• 17 Kubota Y, Tanaka N, Kagota S, Nakamura K, Kunitomo M, Umegaki K. et al . Effects of Ginkgo biloba extract on blood pressure and vascular endothelial response by acetylcholine in spontaneously hypertensive rats.  J Pharm Pharmacol. 2006;  58 243-9.
• 18 Linke A, Erbs S, Hambrecht R. Exercise and the coronary circulation-alterations and adaptations in coronary artery disease.  Prog Cardiovasc Dis. 2006;  48 270-84.
• 19 Bridi R, Crossetti F P, Steffen V M, Henriques A T. The antioxidant activity of standardized extract of Ginkgo biloba (EGb 761) in rats.  Phytother Res. 2001;  15 449-51.
• 20 Carini M, Aldini G, Rossoni G, Morazzoni P, Facino R M. Complexation of Ginkgo biloba extract with phosphatidylcholine improves cardioprotective activity and increases the plasma antioxidant capacity in the rat.  Planta Med. 2001;  67 326-30.
• 21 Kubota Y, Tanaka N, Umegaki K, Takenaka H, Mizuno H, Nakamura K. et al . Ginkgo biloba extract-induced relaxation of rat aorta is associated with increase in endothelial intracellular calcium level.  Life Sci. 2001;  69 2327-36.
• 22 Sun B L, Xia Z L, Yang M F, Ge B L. Effects of Ginkgo biloba extract on cerebral ischemia during early stage of subarachnoid hemorrhage.  Chin J Pathophysiol. 2000;  16 266-8.
• 23 Lippy P. Inflammation in atherosclerosis.  Nature. 2002;  420 868-74.
• 24 Griffiths K A, Sader M A, Skilton M R, Harmer J A, Celermajer D S. Effects of raloxifene on endothelium-dependent dilation, lipoproteins, and markers of vascular function in postmenopausal women with coronary artery disease.  J Am Coll Cardiol. 2003;  42 698-704.
• 25 Zhang W D, Chen H, Zhang C, Liu R H, Li H L, Chen H Z. Astragaloside IV from Astragalus membranaceus shows cardioprotection during myocardial ischemia in vivo and in vitro .  Planta Med. 2006;  72 4-8.
• 26 Nishida S, Satoh H. Mechanisms for the vasodilations induced by Ginkgo biloba extract and its main constituent, bilobalide, in rat aorta.  Life Sci. 2003;  72 2659-67.
• 27 Krieglstein J, Beck T, Seibert A. Influence of an extract of Ginkgo biloba on cerebral blood flow and metabolism.  Life Sci. 1986;  39 2327-34.