The importance of scavenging reactive oxygen species in anti‐aging medicine

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‐PGF2α, 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.

Combined lowering of low grade systemic inflammation and insulin resistance in metabolic syndrome patients treated with Ginkgo biloba

“…No statins, no calcium antagonists and no nitrite compounds were given. No adverse events occurred and all the patients felt well during and after ginkgo intake [5,6].…”

The significance of lipid peroxidation in cardiovascular disease

“…In a number of investigations [1,[3][4][5][6][7][8][9][10], a good correlation has been observed between in vivo biomarkers and risk factors, on one hand, and lipoprotein risk factor deposition to HS-PG under accelerated in vitro conditions. While the latter could most realistically be performed with endothelial cells adhered to methylated silica surfaces for ellipsometry and microscopy, analogous results were found with simpler and more robust endothelial model surfaces, in which HS-PG was simply adsorbed to methylated silica surfaces [13].…”

“…The project has been reviewed and approved by the local Ethics Committee and the Bulgarian Drug Agency. the patients felt well during and after ginkgo intake [6]. After 2-month medication, the second 45 mL blood sample was taken.…”

“…Our clinical trials with statins [3,4], ginkgo [6,10], ω3-fatty acids [11] and blackcurrant extract [12] unravelled this network of biomarker interactions and demonstrated its usefulness for theranostics.…”

“…From a series of previous preclinical and clinical studies it appeared, that many biomarkers, e.g., hs-CRP, cytokines, and liver values are up-or down-regulated in the subthreshold range, but so much the more have an important early diagnostic, preventive and prognostic significance [4][5][6][7][8][9]. The picture is the more complicated in that some inflammatory biomarkers, e.g., MPO and Lp(a) behave inversely with regards to cytokine balance.…”