Browsing by Author "Hussain, Aamir"
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Item Open Access Anthocyanins and Vascular Health: A Matter of Metabolites(MDPI, 2023-04-26) Festa, Joseph; Hussain, Aamir; Al-Hareth, Zakia; Singh, Harprit; Da Boit, MariasoleAnthocyanins are a subgroup of flavonoid polyphenols previously investigated for improv ing cardiovascular health and preventing the development of endothelial dysfunction. However, their poor bioavailability raises the question of whether the observed biological activity is due to their metabolites. Phenolic metabolites can reach higher plasma concentrations and can persist in the circulation for periods much longer than their original anthocyanin form; therefore, the biological activity and health promoting effects of anthocyanins may differ from their metabolites. To address this, recent studies have facilitated different cell models, in vivo studies and explored physiologically relevant concentrations to better understand their mechanisms of action. The criteria were chosen based on previous reports demonstrating that anthocyanins can improve endothelial function via modulation of the Akt-endothelial nitric oxide synthase pathway and transcription factors Nrf2 and NF-κB, which made it critical to assess the phenolic metabolites’ modes of action via these pathways. This review demonstrates how phenolic metabolites differ in bioactivity from their precursor an thocyanin, demonstrating improved endothelial function in response to inflammatory mediators at concentrations that are tolerated in vivo. The review highlights the crucial need for further studies to focus on improving the bioavailability of metabolites in isolation and explore the effect of metabolites in mixtures.Item Metadata only Elderberries as a potential supplement to improve vascular function in a SARS-CoV-2 environment(Wiley, 2022-02-03) Festa, Joseph; Singh, Harprit; Hussain, Aamir; Da Boit, MariasoleCoronavirus disease 2019 (COVID-19) pandemic has been triggered by the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Although recent studies demonstrate that SARS-CoV-2 possibly does not directly infect endothelial cells (EC), the endothelium may be affected as a secondary response due to the damage of neighboring cells, circulating pro-inflammatory cytokines, and/or other mechanisms. Long-term COVID-19 symptoms specifically nonrespiratory symptoms are due to the persistence of endothelial dysfunction (ED). Based on the literature, anthocyanins a major subgroup of flavonoid polyphenols found in berries, have been well researched for their vascular protective properties as well as the prevention of cardiovascular disease (CVD)-related deaths. Elderberries have been previously used as a natural remedy for treating influenza, cold, and consequently cardiovascular health due to a high content of cyanidin-3-glucoside (C3G) a major anthocyanin found in the human diet. The literature reported many studies demonstrating that EE has both antiviral and vascular protective properties that should be further investigated as a nutritional component used against the (in)direct effect of SARS-CoV-2 in vascular function.Item Open Access Elderberry extract improves molecular markers of endothelial dysfunction linked to atherosclerosis(Wiley, 2023-05-10) Festa, Joseph; Hussain, Aamir; Hackney, Amon; Desai, Unmesh; Sahota, T. S.; Singh, Harprit; Da Boit, MariasoleEndothelial dysfunction (ED), secondary to diminished nitric oxide (NO) production and oxidative stress, is an early subclinical marker of atherosclerosis. Reduced NO bioavailability enhances the adhesion of monocytes to endothelial cells and promotes atherosclerosis. Elderberry extract (EB) is known to contain high levels of anthocyanins which could exert vascular protective effects. Specifically, we investigated the functional capacity of EB on various markers of ED. Human umbilical vein endothelial cells (HUVEC) were pretreated with EB 50 μg/mL and stimulated with TNF-α 10 ng/mL. Cell viability, apoptosis, oxidative stress; eNOS, Akt, Nrf2, NOX-4, and NF-κB at the protein level were measured. A co-culture model was used to determine whether EB could prevent the adhesion of monocytes (THP-1) to HUVECs. Moreover, the expression of adhesion molecules and pro-inflammatory cytokines were also measured. It was demonstrated that EB prevented TNF-α induced apoptosis and reactive oxygen species production in HUVECs. Additionally, EB upregulated Akt and eNOS activity, and Nrf2 expression in response to TNF-α, whereas it decreased NOX-4 expression and NF-κB activity. EB prevented the adhesion of monocytes to HUVECs, as well as reduced IL-6 and MCP-1 levels, which was associated with inhibition of VCAM-1 expression. Our results demonstrate that EB upregulates key cellular markers of endothelial function and ameliorates markers of ED. EB could be used as a potential nutritional aid for preventing atherosclerosis progression.Item Metadata only Elderberry extract inhibits tumour necrosis factor induced monocyte adhesion to endothelial cells via modulation of the NF-κB pathway(Oxford University Press, 2022-06-10) Festa, Joseph; Singh, Harprit; Hussain, Aamir; Da Boit, MariasoleItem Metadata only Perception of the Importance of Inherited Genetics and Lifestyle on the Development of Chronic Diseases: A UK Cross‐Sectional Survey(Wiley, 2025-01-05) Hussain, Aamir; Santos-Merx, Lourdes; Da Boit, MariasoleBackground and Aims There is emerging evidence that genes, lifestyles and environment play a prominent role in the development of non-communicable diseases. Currently, there is not information on people's perception of inherited genetics vs. lifestyle on disease development. Knowing people's belief on disease etiology will better inform public health strategies for the adoption of a healthy lifestyle. Methods Individuals aged 18 years and over were recruited in 2019 among the UK population and 363 participants completed an anonymous questionnaire. The main outcomes assessed were perception of importance of inherited genes and lifestyle on the development of diseases. T-tests and χ2 were used. Results The score for the importance of inherited genes in disease development was significantly lower than the lifestyle score (7.5 ± 1.7 vs. 8.5 ± 1, p <0.001). Moreover, the majority of the respondents chose lifestyle over inherited genes as most important factor for cancer, cardiovascular disease and Type 2 Diabetes development (50.8% vs. 29.6%, 79% vs. 11.9%, 85.7% vs. 9.6%; respectively), while 60.6% of respondents selected inherited genes for rheumatoid arthritis (p < 0.05). Knowledge about genes or a healthy lifestyle did not influence the selection of lifestyle as the most important factor (p > 0.05). Conclusion Overall, participants were well aware of the importance of lifestyle as a determinant risk factor for chronic disease development. This is an important step toward adopting a healthy lifestyle.Item Metadata only Phenolic Metabolites Protocatechuic Acid and Vanillic Acid Improve Nitric Oxide Bioavailability via the Akt-eNOS Pathway in Response to TNF-α Induced Oxidative Stress and Inflammation in Endothelial Cells(MDPI, 2024-11-11) Festa, Joseph; Hussain, Aamir; Al-Hareth, Zakia; Bailey, Stephen J.; Singh, Harprit; Da Boit, MariasoleBackground/Objectives: Reduced nitric oxide (NO) bioavailability secondary to excess-superoxide-driven oxidative stress is central to endothelial dysfunction. Previous studies suggest that phenolic metabolites may improve NO bioavailability, yet limited research is available in response to an inflammatory mediator. Therefore, we assessed the effects of cyanidin-3-glucoside (C3G) and its phenolic metabolites protocatechuic acid (PCA) and vanillic acid (VA) on NO bioavailability in a TNF-α induced inflammatory environment. Methods: Primary human umbilical vein endothelial cells (HUVECs) were supplemented with either C3G, PCA, or VA at 1 μM for 24 h before being stimulated with TNF-α 20 ng/mL for an additional 24 h. Measurements included cell viability, apoptosis, reactive oxygen species (ROS), nitrite concentrations, and endothelial nitric oxide synthase (eNOS) and Akt at the mRNA and protein level. Results: Phenolic metabolites did not increase the eNOS expression or nitrite levels in the unstimulated environment; rather, the metabolites mediated NO bioavailability in response to TNF-α induced oxidative stress, with increased viability, eNOS mRNA, phosphorylation, and nitrite levels. Conclusions: Phenolic metabolites, in the presence of TNF-α, can improve NO bioavailability at physiologically relevant concentrations via the Akt-eNOS pathway. This demonstrates that the induction of inflammation is a prerequisite for phenolic metabolites to promote protective properties in endothelial cells by activating the Akt-eNOS pathway.Item Open Access Potential Benefits of Berry Anthocyanins on Vascular Function(Wiley, 2021-08-03) Festa, Joseph; Hussain, Aamir; Da Boit, Mariasole; Singh, HarpritItem Open Access Synthesis and Biological Evaluation of Chalcone Scaffolds as Potential Antiangiogenic Agents.(De Montfort University, 2018) Hussain, AamirAngiogenesis is an integral part of tumour growth and development. Endothelial cell proliferation, migration and differentiation are the main hallmarks of this physiological process. From this, the use of antiangiogenic therapy have brought about a range of licensed FDA approved agents (that are also used by the NHS), that aim to regress tumour induced angiogenesis. However, issues such as: drug resistance, evasion and poor efficacy have limited the use of antiangiogenic therapy as a main stake in anti-cancer therapy. The need for multi-targeted or combinatorial therapies are ever more needed to enhance the current use of these drugs. Therefore, in an attempt to identify novel compounds that exhibit antiangiogenic activity, a group of 1-3-diphenylpropenones (chalcones) were designed, synthesised and biologically evaluated using AH1 (2-chloro-2’5’-dihydroxychalcone) as the parent compound. Methods: Chalcones were synthesised using variations of the Clasien-Schmidt condensation reaction, to develop a compound library based on AH1 (the parent compound). Thereafter, using HUVECs as an angiogenesis model, the effects of the compounds on HUVEC proliferation and migration were evaluated. This was carried out using the MTT cell proliferation assay and the wound healing “scratch” assay. Therein mechanistic evaluation was carried via gel electrophoresis and chemiluminescence western blot. Main findings: Structure activity relationships (SARs) studies identified, that novel compounds AH9 (2-bromo-2’5’-dihydroxychalcone) and AH12 (2-nitro-2’5’-dihydroxychalcone) were shown to exhibit strong anti-proliferative activity along with AH1. Other synthesised derivatives containing different functional groups such as, alkoxy, halogen and methyl did not exhibit similar activities to AH1. The culmination of structure activity relationship suggested that 2’5’-dihydroxy moiety was important to the observed activity only in conjunction with 2-chloro or now 2-bromo substitution on the other phenyl ring. Due to AH9’s better drug likeness over AH12, AH9 and AH1 were taken forward as the lead candidates. Anti-migratory analysis of lead candidates and licensed drug Sorafenib were conducted against HUVECs. AH9 (p < 0.0007) was shown to exhibit significantly more potent inhibitory effects on endothelial migration than AH1 (p = 0.19) and Sorafenib (p = 0.41) over the 8 hour time course study when compared to the untreated control. Mechanistic evaluation identified that AH9 could be exerting its anti-proliferative and potent anti-migratory activity via inhibiting ERK kinase phosphorylation, this was seen at 10μM (p < 0.0001). Discussion and conclusion: To summarise, anti-proliferative and potent anti-migratory activity, towards HUVECs, of a novel molecule AH9 have been identified showing significant effects against two hallmarks of the angiogenesis cascade. AH9 presents a strong case as an agent capable of being developed as an angiogenesis inhibitor for anti-angiogenic therapy.