RESUMEN
Nanoplastics (NPs), plastic particles ranging from 1 to 100 nm are ubiquitous environmental pollutants infiltrating ecosystems. Their small size and widespread use in various products raise concerns for human health, particularly their association with cardiovascular diseases (CVD). NPs can enter the human body through multiple routes, causing oxidative stress, and leading to the senescence and dysfunction of endothelial cells (ECs). Although there are potential natural compounds for treating CVD, there is limited research on preventing CVD induced by NPs. This study investigates the efficacy of Ecklonia cava extract (ECE) in preventing NPs-induced premature vascular senescence and dysfunction. Exposure of porcine coronary arteries (PCAs) and porcine coronary ECs to NPs, either alone or in combination with ECE, demonstrated that ECE mitigates senescence-associated ß-galactosidase (SA-ß-gal) activity induced by NPs, thus preventing premature endothelial senescence. ECE also improved NPs-induced vascular dysfunction. The identified active ingredient in Ecklonia cava, 2,7'-Phloroglucinol-6,6'-bieckol (PHB), a phlorotannin, proved to be pivotal in these protective effects. PHB treatment ameliorated SA-ß-gal activity, reduced oxidative stress, restored cell proliferation, and decreased the expression of cell cycle regulatory proteins such as p53, p21, p16, and angiotensin type 1 receptor (AT1), well known triggers for EC senescence. Moreover, PHB also improved NPs-induced vascular dysfunction by upregulating endothelial nitric oxide synthase (eNOS) expression and restoring endothelium-dependent vasorelaxation. In conclusion, Ecklonia cava and its active ingredient, PHB, exhibit potential as therapeutic agents against NPs-induced premature EC senescence and dysfunction, indicating a protective effect against environmental pollutants-induced CVDs associated with vascular dysfunction.
Asunto(s)
Senescencia Celular , Dioxinas , Phaeophyceae , Senescencia Celular/efectos de los fármacos , Animales , Porcinos , Células Endoteliales/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Floroglucinol/farmacología , Floroglucinol/análogos & derivados , NanopartículasRESUMEN
Impaired function and decreasing numbers of pancreatic ß cells are key factors in the development of type 2 diabetes. This study investigated whether 2,7â³-phloroglucinol-6,6'-bieckol protects INS-1 cells against high glucose-induced glucotoxicity and apoptosis. High glucose (30â¯mM) treatment led to glucotoxicity and induced apoptosis in INS-1 cells. However, treatment with 10-50⯵M 2,7â³-phloroglucinol-6,6'-bieckol significantly reduced glucotoxicity (22.4%) and increased cell viability (up to 80.9%). Treatment with 2,7â³-phloroglucinol-6,6'-bieckol caused a dose-dependent decrease in intracellular reactive oxygen species, lipid peroxidation, and nitric oxide levels, which are increased in INS-1 cells exposed to high glucose. The level of intracellular reactive oxygen species, lipid peroxidation, and nitric oxide levels in INS-1 cells treated with 30â¯mM glucose and 50⯵M 2,7â³-phloroglucinol-6,6'-bieckol (101.9%, 0.11 % and 102.1%) was similar to that of the control group (100%). Furthermore, 2,7â³-phloroglucinol-6,6'-bieckol significantly reduced the levels of pro-apoptotic Bax, caspase 9, and caspase 3 proteins, and increased the levels of the anti-apoptotic Bcl-2 protein and poly ADP-ribose polymerase. The Bcl-2/Bax ratio was 6-fold higher in 50⯵M 2,7â³-phloroglucinol-6,6'-bieckol-treated INS-1 cells than in untreated cells. Apoptotic cells were identified using annexin V/propidium iodide staining, and cells treated with 50⯵M 2,7â³-phloroglucinol-6,6'-bieckol, the numbers of late apoptotic cells decreased over 2-fold compared to that observed in cells treated with 30â¯mM glucose. Overall, these results suggest that 2,7â³-phloroglucinol-6,6'-bieckol has the potential for use as a pharmaceutical agent to protect pancreatic ß cells against high glucose-induced apoptosis.