Perindopril and losartan attenuate pro-coagulation factors in human adipocytes exposed to SARS-CoV-2 spike protein.

Thrombotic events are highly prevalent in coronavirus disease 2019 (COVID-19), especially in patients presenting with risk factors of adverse outcomes such as obesity. Recently, the associations between the angiotensin converting enzyme 2 (ACE2) pathway and thrombosis have been reported. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARBs) are widely used cardiovascular pharmacologic agents that upregulate ACE2 levels. An observation of the alterations in pro-coagulation factors after exposure to ACEIs and ARBs may provide valuable insight into the thrombosis mechanism and how it may relate to ACE2. This study use adipose tissue harvested from an obese male donor was isolated and exposed to perindopril, losartan, and ACE2 recombinant as binding assay, following exposure with 10 nm of SARS-CoV-2 S1 spike protein. After 48 hours, tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) as pro-coagulation factors as well as ACE2 levels and binding evaluated. The results shows TF level was significantly reduced in Perindopril group compared to control (4.834; p=0.005), while a non-significant reduction was observed in Losartan group (5.624; p=0.111). However, Losartan group showed a better reduction of PAI-1 levels (2.633; p≤0.001) than Perindopril group (3.484; p=0.001). These findings were consistent with the observations in ACE2 recombinant group, suggesting that both drugs lowered the bindings of ACE2 and SARS-CoV-2 spike proteins. This study indicated that both perindopril and losartan may attenuate pro-coagulation factors in human adipocytes exposed to SARS-CoV-2 spike proteins, and therefore showcased a potential role of ACE2 in the mechanism of COVID-19-related thrombosis. Further investigation in non-COVID-19 populations should commence and may be of value to expanding this potential in general cardiovascular diseases.

Effect of Nigella sativa Supplementation on Oxidative Stress and Antioxidant Parameters: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Nigella sativa is a commonly used traditional medicine which has been shown to have antioxidant properties. However, its supplementation in patients of clinical trials showed conflicting results. Materials and Method. Relevant articles were searched through PubMed/Medline, SCOPUS, and Google Scholar databases using "Nigella sativa" or "black seed" or "black caraway" or "thymoquinone" and "oxidative stress" or "antioxidant" and "clinical trial" keywords. Randomized, placebo-controlled human interventions using Nigella sativa were included in this study. The methodological quality of studies was assessed using Jadad's quality scales. RESULTS: Five studies using 293 subjects met the inclusion criteria. The overall quality of all included trials was determined based on the low risk of bias and the high quality of reported information (Jadad score ≥ 3). Meta-analysis of 293 eligible subjects showed that treatment with Nigella sativa improved the superoxide dismutase (SOD) level (48.18; 95% CI 30.29 to 66.08; p < 0.01), but there was no significant effect on the malondialdehyde (MDA) level (-5.32; 95% CI -1.19 to 0.128; p=0.114) and total antioxidant capacity (TAC) level (0.219; 95% CI -0.136 to 0.573; p = 0.227). CONCLUSION: This meta-analysis suggests that Nigella sativa supplementation in humans may benefit as an antioxidant by increasing SOD levels but has no significant effect on the MDA level and TAC level.