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Dendrobine modulates autophagy to alleviate ox‐LDL‐induced oxidative stress and senescence in HUVECs

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Dendrobine has potential advantages in suppressing atherosclerosis (AS). FK506‐binding protein 1A (FKBP1A) is implicated in the regulation of autophagy, inflammation, and apoptosis. To reveal the mechanism by which dendrobine inhibits… Click to show full abstract

Dendrobine has potential advantages in suppressing atherosclerosis (AS). FK506‐binding protein 1A (FKBP1A) is implicated in the regulation of autophagy, inflammation, and apoptosis. To reveal the mechanism by which dendrobine inhibits AS by modulating autophagy, oxidative stress, apoptosis, and senescence. An in vitro AS cell model was induced by culturing human umbilical vein endothelial cells (HUVECs) with oxidized low‐density lipoprotein (ox‐LDL). The cells were treated with dendrobine alone or in combination with short hairpin RNA (shRNA) targeting FKBP1A or together with 3‐methyladenine (3MA), an autophagy inhibitor. Inflammatory cytokines levels tumor necrosis factor‐α, interleukin‐6 (IL‐6), and IL‐1β were analyzed and oxidative stress levels were detected by the analysis of reactive oxygen species, malondialdehyde, and superoxide dismutase levels, followed by the analysis of apoptosis levels through terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Cell senescence was evaluated by senescence‐associated β‐galactosidase and light chain 3 (LC3) levels were detected by immunofluorescence (IF) staining. The targeting relationship of dendrobine and FKBP1A was predicted by SwissTarget, PyMol, Autodock, and Open Babel software. Dendrobine reduced the levels of proinflammation factors, oxidative stress levels, apoptosis levels, and senescence phenotype in ox‐LDL‐induced HUVECs. Besides, cell viability has an opposite change. Furthermore, there was an increase in LC3 IF tensity, and LC3‐II/I and Beclin1 expressions, and a decrease in p62 expression. However, these effects of dendrobine could be markedly destroyed by shRNA silencing FKBP1A and 3MA. Dendrobine can suppress inflammatory responses, oxidative stress, apoptosis, and senescence via FKBP1A‐involved autophagy ox‐LDL‐treated HUVECs.

Keywords: dendrobine; apoptosis; oxidative stress; senescence; ldl

Journal Title: Drug Development Research
Year Published: 2022

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