Protocatechualdehyde Rescues Oxygen-Glucose Deprivation/Reoxygenation-Induced Endothelial Cells Injury by Inducing Autophagy and Inhibiting Apoptosis via Regulation of SIRT1

Abstract

Background: Oxidative stress-induced endothelial cell death, such as apoptosis and autophagy, plays a critical role in ischemia-reperfusion injury. Protocatechualdehyde (PCA) is a major bioactive component of the traditional Chinese medicine Salvia miltiorrhiza Bunge (Lamiaceae), and it has been proved to be effective in the prevention and treatment of ischemic cardiovascular and cerebrovascular diseases. However, its role in oxidative stress-induced endothelial cell death and its underlying mechanisms remains unclear. This study aims to investigate the effects and mechanisms of PCA on endothelial cell apoptosis and autophagy induced by oxygen-glucose deprivation/reoxygenation (OGD/R) injury.Methods: After OGD/R induction, human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of PCA. Cell viability, apoptosis, and autophagy were detected by Cell Counting Kit-8 assay, flow cytometry, and monodansylcadaverine assay, respectively. Western blot was applied to explore the effects of PCA on the expression levels of relevant protein factors.Results: The results show that PCA significantly promoted cell survival rate and cell proliferation and enhanced the antioxidant activity in OGD/R-induced HUVECs. PCA inhibited HUVECs apoptosis, as evidenced by decreased expression of cleaved-caspase-3, Bcl2-associated X (BAX), and increased expression of Bcl-2. PCA induced autophagy by reducing the expression of P62 while increasing the expression of Beclin-1 and LC3 II/I. Meanwhile, PCA enhanced the expression of Sirtuin 1 (SIRT1) and suppressed the expression of P53. When SIRT1 was inhibited by selisistat or SIRT1 small-interfering RNA, the anti-apoptotic and pro-autophagy abilities of PCA were attenuated.Conclusion: These results demonstrated that PCA rescued HUVECs from OGD/R-induced injury by promoting autophagy and inhibiting apoptosis through SIRT1 and could be developed as a potential therapeutic agent against ischemic diseases.

N‐acetylneuraminic acid modulates SQSTM1/p62 sialyation‐mediated ubiquitination degradation contributing to vascular endothelium dysfunction in experimental atherosclerosis mice

“…Autophagy is a highly conserved cytoprotective process, which mediates the degradation and recycling of intracellular organelles as well as proteins, 11 and plays important roles in endothelial homeostasis. [12][13][14][15] As reported before, SIA is functionally linked to cellular processes like mediating the proliferation of gastric cancer cells as well as osteosarcoma cells through the autophagic pathway. 16,17 Meanwhile, researchers have also found that SIA could activate TLR4/PKC/gp91 signaling pathway to regulate autophagy, 18 and sialic acid(SIA)containing glycosphingolipids could also induce autophagic cell death in astrocytes.…”

Effects and mechanisms of 6-hydroxykaempferol 3,6-di-O-glucoside-7-O-glucuronide from Safflower on endothelial injury in vitro and on thrombosis in vivo

“…Briefly, HUVECs were cultured in a pre-warmed glucose-free DMEM for 12 h. Then, the cells were maintained in hypoxia condition (1% O 2 , 94% N 2 , and 5% CO 2 ) for 4 h, and then returned to normoxic condition (95% air, 5% CO 2 ) with normal medium for 10 h as reoxygenation. Cao et al (2022) reported that protocatechualdehyde at 0.72, 1.45, and 3.62 μM significantly improved cell viability after OGD/R injury (p < 0.01), and thus HGG was tested at similar concentrations, 0.1, 1, and 10 μM, in this study. To determine the effect of HGG, cells were pre-incubated with HGG for 10 h, followed 4 h of OGD and 10 h of reoxygenation (R) (Lv et al, 2020).…”

The roles of liver sinusoidal endothelial cells in liver ischemia/reperfusion injury

“…In addition, traditional Chinese medicines, such as tragaloside IV, Penthorum chinense Pursh, and Salvia miltiorrhiza Bunge, may become novel therapeutic agents to protect against liver damage caused by IRI. [83][84][85] Finally, the mechanisms involved in liver IRI are complex and have not been fully elucidated. As basic researchers, we need to study the combination of different types of I/R in clinical practice, adopt relevant preclinical models, and use more objective methods to study the mechanism of IRI to better understand the roles played by LSECs, provide reliable references, and procure new ideas for the study of clinical liver IRI and its treatment.…”