Etimad Huwait

Atherosclerosis is caused by inflammatory processes that alter the permeability of arterial wall cells and leucocyte recruitment, leading to oxidation of low-density lipoproteins in the artery. The use of dietary polyphenols as antioxidants seems promising. Herein, molecular docking-based screening was initially used to predict the interactions of epicatechin and hydroxytyrosol on multiple cytokines that can trigger atherosclerosis development. Computational results show that epicatechin and hydroxytyrosol interact with the cytokines, namely, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein 1 (MCP-1), granulocyte–macrophage colony-stimulating factor, leukocyte differentiation antigen CD36, and oxidized low-density lipoprotein receptor-1. Cytotoxicity of both the bioactive compounds to human monocytic THP-1 macrophages was evaluated by lactate dehydrogenase and crystal violet assays. ROS activity evaluation was done for the phytocompounds followed by monocyte migration assay for MCP-1. The expression levels of selected biomarkers were further assessed by quantitative polymerase chain reaction. Inhibition of these atherosclerotic biomarkers may limit the atherogenic effect. Notably, these two polyphenols at a concentration of 0–125 µg/mL for 24 h showed no cytotoxicity on THP-1 macrophages and exhibited decreased ROS production and MCP-1 levels. The genes implicated in the early stages of inflammation are potential therapeutic targets to effectively reduce atherogenesis and prevent CVD. The interaction between the selected cytokines and the two natural compounds indicates their potential ability to inhibit the inflammation in vitro and exhibit anti-atherogenic effects. Hence, epicatechin and hydroxytyrosol possess significant anti-atherosclerotic effects and, in combination, could contribute positively to the treatment of atherosclerosis.

Review Therapeutic agents for the management of atherosclerosis from herbal sources: A computational approach Etimad A. Huwait 1,* 1 Department of Biochemistry, Faculty of Sciences, King Abdul Aziz University, Jeddah 21589, Saudi Arabia; ehuwait@kau.edu.sa. * Correspondence: ehuwait@kau.edu.sa (E.A.H.) Citation: Huwait EA. Therapeutic agents for the management of atherosclerosis from herbal sources: A computational approach. Jour. […]

Targeting foam cells reduces the risk and pathophysiology of atherosclerosis, of which they are one of its early hallmarks. The precise mechanism of action of fucoidan, a potential anti-atherogenic drug, is still unknown. Our objective was to assess the ability of fucoidan to regulate expression of ATP-binding cassette transporter A1 (ABCA1) in ox-LDL-induced THP-1 macrophages. Molecular docking was used to predict how fucoidan interacts with anti-foam cell markers, and further in vitro experiments were performed to evaluate the protective effect of fucoidan on modulating uptake and efflux of lipids. THP-1 macrophages were protected by 50 µg/mL of fucoidan and were then induced to form foam cells with 25 µg/mL of ox-LDL. Expression levels were assessed using RT-qPCR, and an Oil Red O stain was used to observe lipid accumulation in THP-1 macrophages. In addition, ABCA1 protein was examined by Western blot, and cellular cholesterol efflux was determined using fluorescently labeled cholesterol. Under a light microscope, decreased lipid accumulation in ox-LDL-induced-THP-1 macrophages pre-treated with fucoidan showed a significant effect, although it did not affect the expression of scavenger receptors (SR-AI and CD36). It is interesting to note that fucoidan dramatically increased the gene and protein expression of ABCA1, perhaps via the liver X receptor-α (LXR-α). Moreover, fucoidan’s ability to increase and control the efflux of cholesterol from ox-LDL-induced THP-1 macrophages revealed how it may alter ABCA1’s conformation and have a major effect on how it interacts with apolipoprotein A (ApoA1). In vitro results support a rationale for predicting fucoidan and its interaction with its receptor targets’ predicted data, hence validating its anti-atherogenic properties and suggesting that fucoidan could be promising as an atheroprotective.

Colorectal cancer (CRC) is one of the most common cancers leading to comorbidities and mortalities globally. The rational of current study was to evaluate the combined epigallocatechin gallate and quercetin as a potent antitumor agent as commentary agent for therapeutic protocol. The present study investigated the effect of epigallocatechin Gallate (EGCG) (150mg) and quercetin (200mg) at different proportions on proliferation and induction of apoptosis in human colon cancer cells (HCT-116). Cell growth, colonogenic, Annexin V in addition cell cycle were detected in response to phytomolecules. Data obtained showed that, the colony formation was inhibited significantly in CRC starting from the lowest concentration tested of 10 µg/mL resulting in no colonies as visualized by a phase-contrast microscope. Data showed a significant elevation in the annexin V at 100 µg/mL EGCG(25.85%) and 150 µg/mL quercetin (48.35%). Moreover, cell cycle analysis showed that this combination caused cell cycle arrest at the G1 phase at concentration of 100 µg/mL (72.7%) and 150 µg/mL (75.25%). The combined effect of epigallocatechin Gallate and quercetin exert antiproliferative activity against CRC, it is promising in alternative conventional chemotherapeutic agent.

Atherosclerosis is a chronic inflammation characterized by macrophage infiltration, lipid deposition, and arterial wall thickening. Prevention of atherosclerosis by nutraceuticals is gaining attention. Myricetin, a dietary flavonol, is claimed to possess anti-atherosclerosis properties. We studied myricetin’s effect on the atherosclerosis-associated molecular mechanism. Cytotoxicity and proliferation testing to check the viability of myricetin-treated THP-1 macrophages and monocyte migration study in the presence and absence of myricetin was performed. The whole transcriptome analysis was conducted using the Affymetrix microarray platform. The Partek genomics suite for detecting differentially expressed genes (DEGs) and ingenuity pathway analysis was used to identify canonical pathways. Cytotoxicity assays exhibited no significant toxicity in THP-1 macrophages treated with different myricetin concentrations (10–200 μM). Genome-wide expression profiling revealed 58 DEGs (53 upregulated and 5 downregulated) in myricetin-treated THP-1 macrophages. Pathway analysis revealed inhibition of LXR/RXR activation and angiogenesis inhibition by thrombospondin-1 and activated phagocytosis in myricetin-treated THP-1 macrophages. The cytotoxicity assay shows myricetin as a safe phytochemical. In vitro and in silico pathway studies on THP-1 macrophages showed that they can inhibit THP-1 monocyte migration and alter the cholesterol efflux mediated via LXR/RXR signaling. Therefore, myricetin could help in the prevention of cell infiltration in atherosclerotic plaque with reduced risk of stroke or brain damage.

Cardiovascular disease (CVD) is causing high mortality worldwide (World Health Organization-WHO, 2015). Atherosclerosis, the hardening and narrowing of arteries caused by the accumulation of fatty acids and lipids (cholesterol plaques), is a main reason of stroke, myocardial infarction, and angina. Present therapies for cardiovascular disease basically use statins such as β-Hydroxy β-methylglutaryl-CoA, with <70% efficacy and multiple side effects. An in vitro investigation was conducted to evaluate the impact of kaempferol, a natural medication, in an atherosclerotic cell model. We used cytotoxicity assays, Boyden chamber invasion assays, and quantitative PCR. Affymetrix microarrays were used to profile the entire transcriptome of kaempferol-treated cell lines, and Partek Genomic Suite was used to interpret the results. Kaempferol was not cytotoxic to THP-1 macrophages. In comparison to the control, kaempferol reduced monocyte migration mediated by monocyte chemotactic protein 1 (MCP-1) by 80%. The qPCR results showed a 73.7-fold reduction in MCP-1 and a 2.5-fold reduction in intercellular adhesion molecule 1 (ICAM-1) expression in kaempferol-treated cells. In interferon gamma (IFN-γ) without kaempferol and IFN-γ with kaempferol treated cells, we found 295 and 168 differentially expressed genes (DEGs), respectively. According to DEG pathway analysis, kaempferol exhibits anti-atherosclerosis and anti-inflammatory characteristics. Kaempferol is an effective and safe therapy for atherosclerosis.

Several diseases, including atherosclerosis, are characterized by inflammation, which is initiated by leukocyte migration to the inflamed lesion. Hence, genes implicated in the early stages of inflammation are potential therapeutic targets to effectively reduce atherogenesis. Algal-derived polysaccharides are one of the most promising sources for pharmaceutical application, although their mechanism of action is still poorly understood. The present study uses a computational method to anticipate the effect of fucoidan and alginate on interactions with adhesion molecules and chemokine, followed by an assessment of the cytotoxicity of the best-predicted bioactive compound for human monocytic THP-1 macrophages by lactate dehydrogenase and crystal violet assay. Moreover, an in vitro pharmacodynamics evaluation was performed. Molecular docking results indicate that fucoidan has a greater affinity for L-and E-selectin, monocyte chemoattractant protein 1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) as compared to alginate. Interestingly, there was no fucoidan cytotoxicity on THP-1 macrophages, even at 200 µg/mL for 24 h. The strong interaction between fucoidan and L-selectin in silico explained its ability to inhibit the THP-1 monocytes migration in vitro. MCP-1 and ICAM-1 expression levels in THP-1 macrophages treated with 50 µg/mL fucoidan for 24 h, followed by induction by IFN-γ, were shown to be significantly suppressed as eight- and four-fold changes, respectively, relative to cells treated only with IFN-γ. These results indicate that the electrostatic interaction of fucoidan improves its binding affinity to inflammatory markers in silico and reduces their expression in THP-1 cells in vitro, thus making fucoidan a good candidate to prevent inflammation.

Atherosclerosis is an important cause of cardiovascular disorders worldwide. Natural botanical drugs have attracted attention due to their antioxidant, anti-inflammatory, and antiatherogenic properties in the treatment of atherosclerosis. Punicalagin is the major bioactive component of pomegranate peel, and has been shown to have antioxidant, anti-inflammatory, antiviral, anti proliferation, and anticancer properties. To explore its antiatherogenic properties at a molecular level, we investigated the genome-wide expression changes that occur in differentiated THP1 cells following treatment with a non-toxic dose of punicalagin. We also conducted a molecular docking simulation study to identify the molecular targets of punicalagin.

Because of their medicinal characteristics, effectiveness, and importance, plant-derived flavonoids have been a possible subject of research for many years, particularly in the last decade. Plants contain a huge number of flavonoids, and Diosmin, a flavone glycoside, is one of them. Numerous in-vitro and in-vivo studies have validated Diosmin’s extensive range of biological capabilities which present antioxidative, antihyperglycemic, anti-inflammatory, antimutagenic, and antiulcer properties. We have presented this review work because of the greater biological properties and influences of Diosmin. We have provided a brief overview of Diosmin, its pharmacology, major biological properties, such as anti-cancer, anti-diabetic, antibacterial, anticardiovascular, liver protection, and neuroprotection, therapeutic approach, potential Diosmin targets, and pathways that are known to be associated with it.

Atherosclerosis is an inflammatory disease mediated by interferon (IFN-γ) in concert with cell adhesion molecules and chemokines. Thymoquinone (TQ), a flavonoid derived from Nigella sativa, is reported to have anti-inflammatory, antioxidant, and cardiovascular protective properties. We evaluated the effects of TQ on the key pathogenic stages of atherosclerosis, including cell viability, inflammatory gene expression, cell migration, and cholesterol efflux, on human THP-1 macrophages in-vitro. Moreover, in-silico analysis was performed to predict the molecular targets and signaling mechanisms. We demonstrated that TQ treatment had no effect on cell viability and decreased the expression of monocyte chemoattractant protein (MCP-1) and intercellular adhesion molecule (ICAM-1) in response to IFN-γ. In addition, we have also demonstrated that the THP-1 cell migration was inhibited by TQ in the absence or presence of MCP-1. Thymoquinone had no effect on cholesterol efflux from monocytes. In-silico analysis also identified several putative targets for TQ that are associated with inflammatory diseases and associated signaling pathways. Collectively, these results suggest that TQ has anti-inflammatory effects and may be a potential nutraceutical candidate for the prevention and treatment of atherosclerosis.