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The importance of scavenging reactive oxygen species in anti‐aging medicine
Authors:Günter Siegel  Annette Schmidt  Petra Schäfer  Martin Malmsten  Lovisa Ringstad  Karl Winkler  Sören Just
Institution:1. Charité–University Medicine Berlin, Campus Benjamin Franklin, Institute of Physiology, D‐14195 Berlin, Germany;2. Department of Physical Chemistry, Institute of Pharmacy, Uppsala University, S‐75123 Uppsala, Sweden;3. Molecular Cardiology, Leibniz‐Institute of Arteriosclerosis Research, University of Münster, D‐48149 Münster, Germany;4. University Clinic Freiburg, Institute of Clinical Chemistry, D‐79106 Freiburg, Germany;5. Heart Center Cottbus, Department of Cardiac Surgery, D‐03048 Cottbus, Germany
Abstract:In a pilot study, we had reported on the beneficial effects of Ginkgo biloba (EGb 761) on arteriosclerotic nanoplaque formation and size in cardiovascular high‐risk patients who had undergone an aortocoronary bypass operation. Briefly, nanoplaque formation and size, the ratio oxLDL/LDL, and the highly atherothrombotic lipoprotein(a) concentration were substantially reduced, while superoxide dismutase activity and the blood concentration of the vasodilating substances cAMP and cGMP were upregulated. Since the arteriosclerosis prophylactic and well‐aging promotive impact of Ginkgo extract has been proven in this pilot study, we wanted to confirm these beneficial effects through a second observational clinical trial. The measurable variables formerly used were additionally supplemented by a wide, novel biomarker spectrum, through which the latest parameters and markers of plaque stability and progression, oxidative stress, and inflammation were available. In eleven patients with metabolic syndrome in the initial stage, the reduction of arteriosclerotic nanoplaque formation amounted to 14.3±2.9% (p<0.0077) and of nanoplaque size to 23.4±3.7% (p<0.0004), respectively, after 2‐months of treatment with Ginkgo biloba extract. Additionally, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were upregulated by 19.6±10.0% (p<0.0785) and 11.6±2.3% (p<0.001), respectively, the quotient oxLDL/LDL lowered by 21.0±4.3% (p<0.002), and lipoprotein(a) concentration decreased by 26.3±4.8% (p<0.001) in the patients' blood. The concentration of cAMP and cGMP was augmented by 43.5±12.0% (p<0.001) and 32.9±10.4% (p<0.001), respectively. Surprisingly, we found a lowering of the serum Ca2+ concentration by 5.4±1.6% (p<0.0076) from 2.37±0.03 to 2.24±0.04 mmol/L (p<0.0069). Apart from an additional vasodilatory effect, the lowered extracellular Ca2+ concentration affects nanoplaque formation restrictively, since this is a Ca2+ driven process. Furthermore, we could show a favourable development of the biomarkers 8‐iso‐PGF, oxLDL/LDL, SOD, GPx (oxidative stress), hs‐CRP, MPO, TNFα, TGFβ1 (inflammatory status) and MMP‐9 (plaque stability). The markers selected here are suited to provide a comprehensive risk profile for the prevention of arteriosclerosis. Finally, a multiple regression analysis reveals a basis for a mechanistic explanation of nanoplaque reduction under Ginkgo treatment. The arteriosclerosis inhibiting effect is due to an attenuation of the risk factors oxLDL/LDL, Lp(a), and Ca2+]o as well as to a significant increase in the vasodilator cAMP and cGMP concentration. Thus, Ginkgo with its pleiotropic effects should be assigned a fixed rank among the anti‐aging medical therapeutics as a prophylactic measure, especially in patients with early‐stage metabolic syndrome.
Keywords:Clinical trial  Ellipsometry  Ginkgo biloba  Metabolic syndrome
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