The effect of Ginkgo biloba (EGb 761) on arteriosclerotic nanoplaque formation and size in a long-term clinical trial

Abstract

Abstract Utilizing the isolated lipoprotein receptor syndecan (heparan/chondroitin sulfate proteoglycan, HS/CS-PG) from arterial endothelium and smooth muscle cell membranes and coating therewith a silica surface, we were able to observe the very earliest stages of arteriosclerotic plaque development, the so-called nanoplaque build-up, by ellipsometric techniques (patent EP 0 946 876). The arteriosclerotic nanoplaque is represented by the ternary aggregational complex of the HS-PG receptor, lipoprotein particles and calcium ions. The model was validated in several clinical studies [1,2] on cardiovascular high-risk patients applying their blood lipoprotein fractions and, among others, proved the inhibiting effect of Ginkgo biloba on nanoplaque formation. In eight high-risk patients who had undergone an aortocoronary bypass operation, the reduction of arteriosclerotic nanoplaque formation amounted to 11.9 ± 2.5% ( p ≤ 0.0078, non-parametric Wilcoxon-test for paired samples; median 10.6%) and of nanoplaque size to 24.4 ± 8.1% ( p ≤ 0.0234, non-parametric Wilcoxon-test for paired samples; median 20.4%), respectively, in normal blood substitute solution with 2.5 mmol/l [Ca 2+ ] after a 2 month therapy with 2 × 120 mg Ginkgo biloba extract (EGb 761, Rokan® novo). Additionally, we could directly demonstrate and confirm the antioxidative capacity of ginkgo and its oxygen free radical scavenging effect by disclosing an upregulation of superoxide dismutase (SOD) activity of 15.7 ± 7.0% ( p ≤ 0.0391, non-parametric Wilcoxon-test for paired samples; median 16.2%) and a lowering of the quotient oxLDL/LDL by 17.0 ± 5.5% ( p ≤ 0.0234, non-parametric Wilcoxon-test for paired samples; median 16.9%) after the 2 month medication regimen. Furthermore, we measured a significant decrease in lipoprotein(a) concentration falling from 52.4 ± 8.2 to 42.0 ± 9.9 mg/dl ( p ≤ 0.0359, paired Student t-test). Altogether, these beneficial effects of Ginkgo biloba might have partially repaired endothelial dysfunction being responsible for the very earliest stages in arteriosclerosis and could present a basis for a mechanistic explanation of nanoplaque reduction under Ginkgo treatment. This further pleiotropic effect of Ginkgo illuminated for the first time in this biosensor-biomembrane approach has immediate relevance for the formation of arteriosclerotic plaques as well as for its prophylactic and therapeutic potential in patients.