Echinacoside activates Nrf2/PPARγ signaling pathway to modulate mitochondrial fusion-fission balance to ameliorate ox-LDL-induced dysfunction of coronary artery endothelial cells

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2024-12, Vol.397 (12), p.9767-9776
• Main Authors: Qiu, Xiandi, Feng, Yuxing
• Format: Article
• Language: English
• Subjects: Angiogenesis; Anti-inflammatory agents; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; Cardiovascular disease; Cardiovascular diseases; Cell fusion; Cell Survival - drug effects; Cell viability; Cells, Cultured; Cholecystokinin; Coronary artery disease; Coronary vessels; Coronary Vessels - drug effects; Coronary Vessels - metabolism; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Flow cytometry; Fluorescein diacetate; Glycosides - pharmacology; Heart diseases; Humans; Immunofluorescence; Lipoproteins, LDL - toxicity; Low density lipoprotein; Membrane fusion; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mitochondrial Dynamics - drug effects; Morbidity; Neurosciences; NF-E2-Related Factor 2 - metabolism; Nitric oxide; Nitric Oxide Synthase Type III - metabolism; Nitric-oxide synthase; Oxidative stress; Oxidative Stress - drug effects; Peroxisome proliferator-activated receptors; Pharmacology/Toxicology; PPAR gamma - agonists; PPAR gamma - metabolism; Signal transduction; Signal Transduction - drug effects
• ISSN: 0028-1298; 1432-1912; 1432-1912
• DOI: 10.1007/s00210-024-03233-1

As a cardiovascular disease, coronary heart disease (CHD) is characterized by poor prognosis and increasing morbidity and mortality rates. Echinacoside (ECH) can protect against multiple cardiovascular diseases due to its antioxidant and anti-inflammatory properties. However, the role of ECH in CHD remains unclear. In ECH-treated human coronary artery endothelial cells (HCAECs), cell viability, NO production, endothelial nitric oxide synthase (eNOS) expression, and angiogenesis ability were detected using cell counting kit-8 (CCK-8) assay, diaminofluorescein-FM diacetate (DAF-FM DA) staining, western blot, and tube formation assay, respectively. The activities of oxidative stress markers were detected using dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay and corresponding assay kits. Cell apoptosis was detected utilizing flow cytometry and caspase3 assay. Western blot was used to detect the expressions of Nrf2/PPARγ signaling pathway- and mitochondrial dynamics-related proteins. Mitochondrial membrane potential and mitochondrial fusion and fission were detected using JC-1 staining and immunofluorescence (IF) assay. In this study, ECH was found to revive the viability, ameliorate the endothelial dysfunction, suppress oxidative stress, and inhibit the apoptosis in ox-LDL-induced HCAECs via activating Nrf2/PPARγ signaling pathway, which were all abolished following the treatment of Nrf2 inhibitor ML385. It was also identified that ECH regulated mitochondrial fusion-fission balance in ox-LDL-induced HCAECs through the activation of Nrf2/PPARγ signaling pathway. In summary, ECH activated Nrf2/PPARγ signaling pathway to regulate mitochondrial fusion-fission balance, thereby improving ox-LDL-induced dysfunction of HCAECs.