The synergistic effect of Citrus bergamia and Cynara cardunculus extracts on vascular inflammation and oxidative stress in non-alcoholic fatty liver disease

Abstract

Background and aim Non-Alcoholic Fatty Liver Disease (NAFLD) represents a risk factor for cardiovascular diseases. NAFLD is worsened by the simultaneous occurrence of type 2 diabetes mellitus (T2DM) causing an enhancement of inflammatory and fibrotic processes. Although insulin resistance appears the link between NAFLD and T2DM, current pharmacological treatments of T2DM failed to produce relevant benefits in preventing T2DM-related liver dysfunction. In this randomized, double blind, placebo-controlled clinical study, we evaluated the effect of Bergacyn, an innovative formulation originating from the combination of Bergamot Polyphenolic Fraction (BPF) and Cynara cardunculus (CyC). Experimental procedure 80 adult patients with a history of at least 12 months of T2DM and NAFLD received orally BPF (300 mg/daily) Cyc (300 mg/daily), separately or formulated in combination 50/50% (Bergacyn; 300 mg/daily), or placebo all containing 300 mg of bergamot albedo fibers micronized and co-grinded as excipients. Results and conclusion Serum measurements and liver ultrasound analyses showed that concomitant administration of BPF and CyC produced significant improvement of NAFLD biomarkers in patients with T2DM. This effect was associated with a substantial reduction of oxidative stress/inflammatory biomarkers, thus contributing to a significant improvement of NO-mediated reactive vasodilation. Furthermore, the effect of Bergacyn showed a synergistic effect of both extracts, thus suggesting that this peculiar formulation represents a novel therapeutic strategy to counteract vascular inflammation and endothelial dysfunction in patients suffering from T2DM and NAFLD. Further studies in larger cohort of diabetic patients are required to better identify the potential of Bergacyn on metabolic disorders accompanying T2DM and NAFLD.

Synergistic effects of black ginseng and aged garlic extracts for the amelioration of nonalcoholic fatty liver disease (NAFLD) in mice

“…Particularly, the HFD+BGE+AGE200 group showed the highest SOD and the lowest MDA, thereby indicating a synergistic effect at this concentration. In a human study, it is shown that Citrus bergamia and Cynara cardunculus extracts in combination produced synergistic effects, which caused lowered MDA while SOD and GPx were increased (Musolino et al., 2020). However, it is important to note that oxidative stress caused by the production of reactive oxygen species (ROS) is neutralized by enzymatic and nonenzymatic antioxidants.…”

Endothelial Dysfunction and Extra-Articular Neurological Manifestations in Rheumatoid Arthritis

“…Due to its peculiarity, it is employed in different formulations such as essential oil, hydro-alcoholic extract, and fruit juice. Recent scientific results have identified massive antioxidant and anti-inflammatory effects on the part of the polyphenolic fraction of bergamot, to the point that this fruit is considered a real nutraceutical [ 163 , 164 , 165 , 166 ]. Following these considerations, bergamot could be a promising candidate for studies of its activity on in vivo models of RA.…”

The Potential Properties of Natural Compounds in Cardiac Stem Cell Activation: Their Role in Myocardial Regeneration

“…BPF directly reduces lipid peroxidation biomarkers (TBARS), MDA, strongly inhibits protein tyrosine nitration levels and prevents ROS accumulation in the nucleus of several cell types [ 222 , 223 , 224 ]. BPF also improves the activity of endogenous antioxidant enzymes, such as SOD, Glutathione Peroxidase (GPx) and Glutathione S Transferase P1 (GSTP1) [ 225 , 226 ]. The additive vaso-protective effect of BPF, related to its antioxidant property, demonstrated its ability to reduce oxidized low-density lipoprotein receptor-1 (LOX-1) expression levels, highly modulated in the development and progression of endothelial dysfunction to atherosclerosis, and increase PKB phosphorylation, providing protection against vascular atherogenic injury in patient with hyperlipemia [ 222 ].…”