Herbal targeting of mitochondrial dynamic proteins in low-density lipoprotein driven atherosclerosis in vitro

Background Mitochondrial dysfunction is a critical early driver of endothelial injury in atherogenesis. Natural plant-derived products targeting mitochondrial quality control represent a promising therapeutic approach, yet their mechanisms in oxidized LDL (ox-LDL)-induced endothelial damage remain underexplored. Methods We evaluated ethanolic extracts from Rosmarinus officinalis , Cynara cardunculus , and Myrtus communis on ox-LDL-induced mitochondrial damage in human umbilical vein endothelial cells (HUVECs). Cell viability (MTT), proliferation (acridine orange staining), and mitochondrial membrane potential (Δψm; Rhodamine 6G) were assessed across therapeutic-equivalent concentrations (×0.1–×100). In a pathophysiologically relevant ox-LDL model (80 μg/mL, 48 h), RT-qPCR analyzed expression of genes regulating mitochondrial dynamics (DRP1, FIS1, MFF, MFN2, OPA1), mitophagy (PINK1, PARKIN, FUNDC1, OPTN, SQSTM1/p62), and antioxidant defense (CAT). Results All three extracts preserved Δψm and mitochondrial network architecture in healthy HUVECs in a dose-dependent manner. In the ox-LDL model, extracts reversed the pro-fission transcriptional shift by downregulating DRP1, FIS1, and MFF while restoring MFN2 and OPA1 expression ( p < 0.05–0.001). C. cardunculus robustly upregulated PINK1 and PARKIN, indicating enhanced ubiquitin-dependent mitophagy, whereas R. officinalis and M. communis preferentially increased FUNDC1 and OPTN, suggesting receptor-mediated clearance pathways. Extract treatment concurrently upregulated endogenous antioxidant enzymes (CAT), suppressed pro-inflammatory MAPK8 (JNK). Conclusions Polyphenol-rich herbal extracts protect endothelial cells from ox-LDL-induced injury by rebalancing mitochondrial fission/fusion dynamics, activating complementary mitophagy pathways, and fortifying antioxidant defenses. These findings support the potential of standardized herbal formulations as targeted adjunctive strategies for early atherosclerosis prevention through mitochondrial quality control.