Abstract
Hyperlipidemia is a risk factor for cardiac damage and cardiovascular disease. Increasing evidence has shown that dyslipidemia-related cardiac damage is associated with lipid accumulation, oxidative stress, and inflammation. Thymoquinone (TQ) is the major constituent of Nigella sativa, commonly known as black seed or black cumin, and is globally used in folk (herbal) medicine for treating and preventing a number of diseases and conditions. Several studies have shown that TQ can protect against cardiac damage. This study is aimed at investigating the possible protective effects of TQ on hyperlipidemia-induced cardiac damage in low-density lipoprotein receptor-deficient (LDL-R−/−) mice. Eight-week-old male LDL-R−/− mice were randomly divided into normal diet (ND), high-fat diet (HFD), and HFD and TQ (HFD+TQ) groups and were fed the different diets for eight weeks. Blood samples were obtained from the inferior vena cava in serum tubes and stored at -80°C until use. Some cardiac tissues were fixed in 10% formalin and then embedded in paraffin for histological evaluation. The remainder of the cardiac tissues was snap-frozen in liquid nitrogen for mRNA preparation or immunoblotting. The levels of metabolism-related factors, such as total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and high-sensitivity C-reactive protein (hs-CRP), were decreased in the HFD+TQ group compared with those in the HFD group. Periodic acid-Schiff staining demonstrated that lipid deposition was lower in the HFD+TQ group than in the HFD group. The expression of pyroptosis indicators (NOD-like receptor 3 (NLRP3), interleukin- (IL-) 1β, IL-18, and caspase-1), proinflammatory factors (IL-6 and tumor necrosis factor alpha (TNF-α)), and macrophage markers (cluster of differentiation (CD) 68) was significantly downregulated in the HFD+TQ group compared with that in the HFD group. Our results indicate that TQ may serve as a potential therapeutic agent for hyperlipidemia-induced cardiac damage.
Highlights
Cardiovascular disease (CVD) is a major cause of mortality and morbidity worldwide [1, 2]
The total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), high-sensitivity C-reactive protein (hs-CRP), IL-6, and TNF-α levels were markedly increased in the high-fat diet (HFD) group but significantly decreased in the HFD and TQ (HFD+TQ) group
Our study showed that the expression of IL-6 and TNF-α was reduced in the HFD+TQ group compared with that in the HFD group, indicating that TQ downregulated the HFD-induced expression of IL-6 and TNF-α
Summary
Cardiovascular disease (CVD) is a major cause of mortality and morbidity worldwide [1, 2]. Among the causes of cardiovascular disease, hyperlipidemia is a critical damageinducing factor [3]; individuals with hyperlipidemia have a higher risk for CVD than those with normal cholesterol levels [4]. Hyperlipidemia is characterized by an increase in triglyceride (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-c) and/or a decrease in highdensity lipoprotein-cholesterol (HDL-C) [5]. Several researchers have investigated various drugs for the treatment of hyperlipidemia, such as statins; as these drugs are related to the development of cell resistance and are associated with adverse effects, new methods for treating hyperlipidemia. The use of natural hypolipidemic drugs may constitute a promising strategy for the prevention and treatment of hyperlipidemia [8]
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