Elucidating the Anti-Senescence Effects of Calophyllum Species and its Underlying Mechanism in Hydrogen Peroxide Induced Premature Senescence in Endothelial Cells
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Universiti Malaysia Sarawak
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Ageing, marked by endothelial cell cycle arrest and changes in metabolic pathways, is recognised as a crucial element in the onset and advancement of cardiovascular diseases (CVDs). Senescent cells play a role in oxidative stress are linked to endothelial dysfunction that ultimately leads to CVDs. Xanthone is a part of a large group of phenolic compounds, active ingredients that can be found in Calophyllum spp. proven to have valuable properties such as antioxidants, antimicrobial and anti-inflammation, inhibit the enzymes that lead to Reactive Oxygen Species (ROS) formation, which is one of the many factors leading to cellular senescence and the development of CVDs. However, the study on the anti-senescence effects of Calophyllum spp. extracts on stress-induced premature senescence (SIPS), which is accelerated cellular ageing that occurs when cells react to a variety of exogenous cellular stressors, including oxidative stress, remain underexplored. Thus, this research aims to explore the anti-senescence effects of Calophyllum spp. extracts on SIPS HUVECs. HUVECs were incubated with H2O2 (25 μM) to establish the SIPS model and treated with various concentrations of ethyl acetate (EA, 5 and 20 μg/ml), and the positive control Apocynin (20 μM) to evaluate the cell viability using phase contrast microscopy and MTT Assay. The senescence markers, senescence-associated β-galactosidase (SA-β-gal), were measured by the SA-β-gal assay. Additionally, the involvement of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) and Cyclooxygenase-2 (COX-2) pathways was analysed using Colorimetric Assay and ELISA Assay. Results demonstrated that H2O2 (25 μM) induced senescence in HUVECs and was then reversed by the EA extract from C. gracilentum and C. soulattri and Apocynin (20 μM). Treatment with EA also upregulated the NADPH levels, indicating the involvement of EA in inhibiting oxidative stress effects in SIPS HUVECs. In contrast, a significant decrease in expression of COX-2 as an inflammatory response, after treatment with EA extract was not portrayed. Taken together, the findings underscore that Calophyllum spp. extracts potential in preventing CVDs by alleviating endothelial senescence and reducing endothelial dysfunctions of SIPS in HUVECs through the inhibition of SA-β-gal and regulation of NADPH but not COX-2.