A Comprehensive Review of the Cardiovascular Protective Properties of Silibinin/Silymarin: A New Kid on the Block

Silibinin/silymarin has been used in herbal medicine for thousands of years and it is well-known for its hepato-protective properties. The present comprehensive literature review aimed to critically summarize the pharmacological properties of silymarin extract and its main ingredient silibinin in relation to classical cardiovascular risk factors (e.g., diabetes mellitus, etc.). We also assessed their potential protective and/or therapeutic application in cardiovascular diseases (CVDs), based on experimental and clinical studies. Pre-clinical studies including in vitro tests or animal models have predominantly implicated the following effects of silymarin and its constituents: (1) antioxidant, (2) hypolipidemic, (3) hypoglycemic, (4) anti-hypertensive and (5) cardioprotective. On the other hand, a direct amelioration of atherosclerosis and endothelial dysfunction after silymarin administration seems weak based on scarce data. In clinical trials, the most important findings are improved (1) glycemic and (2) lipid profiles in patients with type 2 diabetes mellitus and/or hyperlipidemia, while (3) the anti-hypertensive effects of silibinin/silymarin seem very modest. Finally, the changes in clinical endpoints are not robust enough to draw a firm conclusion. There are significant limitations in clinical trial design, including the great variety in doses and cohorts, the underlying conditions, the small sample sizes, the short duration and the absence of pharmacokinetic/pharmacodynamic tests prior to study commitment. More data from well-designed and high-quality pre-clinical and clinical studies are required to firmly establish the clinical efficacy of silibinin/silymarin and its possible therapeutic application in cardiovascular diseases

Corpuscular Fragility and Metabolic Aspects of Freshly Drawn Beta-Thalassemia Minor RBCs Impact Their Physiology and Performance Post Transfusion: A Triangular Correlation Analysis In Vitro and In Vivo

The clarification of donor variation effects upon red blood cell (RBC) storage lesion and transfusion efficacy may open new ways for donor–recipient matching optimization. We hereby propose a “triangular” strategy for studying the links comprising the transfusion chain—donor, blood product, recipient—as exemplified in two cohorts of control and beta-thalassemia minor (βThal+) donors (n = 18 each). It was unraveled that RBC osmotic fragility and caspase-like proteasomal activity can link both donor cohorts to post-storage states. In the case of heterozygotes, the geometry, size and intrinsic low RBC fragility might be lying behind their higher post-storage resistance to lysis and recovery in mice. Moreover, energy-related molecules (e.g., phosphocreatine) and purine metabolism factors (IMP, hypoxanthine) were specifically linked to lower post-storage hemolysis and phosphatidylserine exposure. The latter was also ameliorated by antioxidants, such as urate. Finally, higher proteasomal conservation across the transfusion chain was observed in heterozygotes compared to control donors. The proposed “triangularity model” can be (a) expanded to additional donor/recipient backgrounds, (b) enriched by big data, especially in the post-transfusion state and (c) fuel targeted experiments in order to discover new quality biomarkers and design more personalized transfusion medicine schemes

The Post-Storage Performance of RBCs from Beta-Thalassemia Trait Donors Is Related to Their Storability Profile

Blood donors with beta-thalassemia traits (βThal+) have proven to be good “storers”, since their stored RBCs are resistant to lysis and resilient against oxidative/proteotoxic stress. To examine the performance of these RBCs post-storage, stored βThal+ and control RBCs were reconstituted in plasma donated from transfusion-dependent beta-thalassemic patients and healthy controls, and incubated for 24 h at body temperature. Several physiological parameters, including hemolysis, were evaluated. Moreover, labeled fresh/stored RBCs from the two groups were transfused in mice to assess 24 h recovery. All hemolysis metrics were better in the group of heterozygotes and distinguished them against controls in the plasma environment. The reconstituted βThal+ samples also presented higher proteasome activity and fewer procoagulant extracellular vesicles. Transfusion to mice demonstrated that βThal+ RBCs present a marginal trend for higher recovery, regardless of the recipient’s immune background and the RBC storage age. According to correlation analysis, several of these advantageous post-storage characteristics are related to storage phenotypes, like the cytoskeleton composition, low cellular fragility, and enhanced membrane proteostasis that characterize stored βThal+ RBCs. Overall, it seems that the intrinsic physiology of βThal+ RBCs benefits them in conditions mimicking a recipient environment, and in the circulation of animal models; findings that warrant validation in clinical trials