Ethyl Rosmarinate Protects High Glucose-Induced Injury in Human Endothelial Cells

• Published in: Molecules (Basel, Switzerland) Vol. 23; no. 12; p. 3372
• Main Authors: Shen, Yan-Hui, Wang, Li-Ying, Zhang, Bao-Bao, Hu, Qi-Ming, Wang, Pu, He, Bai-Qiu, Bao, Guan-Hu, Liang, Jing-Yu, Wu, Fei-Hua
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19.12.2018; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Annexin V; Anthracenes - pharmacology; Apoptosis; Apoptosis - drug effects; Bcl-2 protein; c-Jun protein; Caspase-3; Cell Survival - drug effects; Cell viability; Cells, Cultured; Chromones - pharmacology; Cinnamates - pharmacology; Depsides - pharmacology; Diabetes; Diabetes mellitus; Endothelial cells; Endothelial Cells - cytology; Enzyme inhibitors; ethyl rosmarinate; Glucose; Glucose - adverse effects; high glucose; Humans; Hyperglycemia; JNK protein; Kinases; Molecular docking; Molecular Docking Simulation; Morpholines - pharmacology; NF-kappa B - metabolism; NF-κB protein; Oxidative Stress - drug effects; Phosphatidylinositol 3-Kinase - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Reactive Oxygen Species - metabolism; Rosmarinic Acid; Signal Transduction - drug effects; Staining; Transcription factors; vascular endothelial cell; apoptosis; rosmarinic acid; high glucose; ethyl rosmarinate; vascular endothelial cell
• DOI: 10.3390/molecules23123372
• ISSN: 1420-3049

Ethyl rosmarinate (RAE) is one of the active constituents from (Benth.) O. Kuntze, which is used for diabetic treatment in Chinese folk medicine. In this study, we investigated the protective effect of RAE on high glucose-induced injury in endothelial cells and explored its underlying mechanisms. Our results showed that both RAE and rosmarinic acid (RA) increased cell viability, decreased the production of reactive oxygen species (ROS), and attenuated high glucose-induced endothelial cells apoptosis in a dose-dependent manner, as evidenced by Hochest staining, Annexin V⁻FITC/PI double staining, and caspase-3 activity. RAE and RA both elevated Bcl-2 expression and reduced Bax expression, according to Western blot. We also found that LY294002 (phosphatidylinositol 3-kinase, or PI3K inhibitor) weakened the protective effect of RAE. In addition, PDTC (nuclear factor-κB, or NF-κB inhibitor) and SP600125 (c-Jun N-terminal kinase, or JNK inhibitor) could inhibit the apoptosis in endothelial cells caused by high glucose. Further, we demonstrated that RAE activated Akt, and the molecular docking analysis predicted that RAE showed more affinity with Akt than RA. Moreover, we found that RAE inhibited the activation of NF-κB and JNK. These results suggested that RAE protected endothelial cells from high glucose-induced apoptosis by alleviating reactive oxygen species (ROS) generation, and regulating the PI3K/Akt/Bcl-2 pathway, the NF-κB pathway, and the JNK pathway. In general, RAE showed greater potency than RA equivalent.