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

Abstract

Ethyl rosmarinate (RAE) is one of the active constituents from Clinopodium chinense (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.

Ethyl Rosmarinate Prevents the Impairment of Vascular Function and Morphological Changes in L-NAME-Induced Hypertensive Rats

“…These results indicated that ethyl rosmarinate promoted vasorelaxation, which may be related to the increase in eNOS which then increases the response to ACh with no alteration in vascular smooth muscle cell integrity. These results are in accordance with previous studies that stated that rosmarinic acid dilated aortic rings with an endothelium-dependent pathway and prevented endothelial cell damage in high-glucose conditions [16,33].…”

Gypenosides Inhibit Inflammatory Response and Apoptosis of Endothelial and Epithelial Cells in LPS-Induced ALI: A Study Based on Bioinformatic Analysis and in vivo/vitro Experiments

“…After LPS stimulation, the levels of p-p65 was increased dose dependently ( Figure 6A ). In line with the results of GPs in vivo, LPS co-treated with GPs could inhibit the expression of p-p65, just as ammonium pyrrolidinedithiocarbamate (PTDC), a widely used NF-κB pathway inhibitor 23 , 24 ( Figure 6B and C ) and the cytokines of TNF-α, IL-1β, IL-6, VCAM1 in HPMEC ( Figure 6D ), indicating GPs reduced the cytotoxicity of LPS to HPMEC.

Figure 6 GPs alleviated inflammatory response in endothelial cells.

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GC-MS and HPLC-ESI-MS-MS Characterization of Sanchezia oblonga (Acanthaceae) Extracts

“…Synapic acid derivatives exhibited antioxidant, antimicrobial, anti-inflammatory, anti-cancer, anti-anxiety (Nićiforović et al, 2017), anti-glycemic, neuroprotective, antibacterial (Chen, 2016) and analgesic activities (Hameed et al, 2016). Rosmarinic acid esters exhibited a broad spectrum of biological effects (Shen et al, 2018;Liang et al, 2017;Thammason et al, 2018). Glycerol phenylpropanoid glucosides act as hepatic glucose production inhibitors; structure-activity relationships indicated that the hydroxylation pattern of the hydroxycinnamic acid moiety and acetylation accounted for differences in activity (Murray et al, 2019).…”

“…The mass spectra of compounds 24 (Rt -10.3 min) and 26 (Rt -11.0 min) displayed the same [M -H]at m/z 387. The mass spectrum of compound 24 (Rt -10.3 min) exhibited base peak at m/z 163, that resulted to the loss of 225 Da from the molecular ion at m/z 387, which was formed by cleavage of the ester bond (Aziz et al, 2014;Shen et al, 2018;Wicha et al, 2015). Compound 24 was tentatively identified as ethyl rosmarinate.…”