ApoA-I Nanoparticles as Curcumin Carriers for Cerebral Endothelial Cells: Improved Cytoprotective Effects against Methylglyoxal

Abstract

Methylglyoxal (MGO) is a highly reactive metabolite of glucose present at elevated levels in diabetic patients. Its cytotoxicity is associated with endothelial dysfunction, which plays a role in cardiovascular and cerebrovascular complications. Although curcumin has many therapeutic benefits, these are limited due to its low bioavailability. We aimed to improve the bioavailability of curcumin and evaluate a potential synergistic effect of curcumin and reconstituted high-density lipoprotein (rHDL) nanoparticles (Cur-rHDLs) on MGO-induced cytotoxicity and oxidative stress in murine cerebrovascular endothelial cells (bEnd.3). Cur-rHDL nanoparticles (14.02 ± 0.95 nm) prepared by ultracentrifugation and containing curcumin were quantified by LC–MS/MS. The synergistic effect of cur-rHDL nanoparticles was tested on bEnd.3 cytotoxicity, reactive oxygen species (ROS) production, chromatin condensation, endoplasmic reticulum (ER) stress, and endothelial barrier integrity by impedancemetry. The uptake of curcumin, alone or associated with HDLs, was also assessed by mass spectrometry. Pretreatment with Cur-rHDLs followed by incubation with MGO showed a protective effect on MGO-induced cytotoxicity and chromatin condensation, as well as a strong protective effect on ROS production, endothelial cell barrier integrity, and ER stress. These results suggest that Cur-rHDLs could be used as a potential therapeutic agent to limit MGO-induced dysfunction in cerebrovascular endothelial cells by enhancing the bioavailability and protective effects of curcumin.

Umbelliferone protects against methylglyoxal‐induced HUVECs dysfunction through suppression of apoptosis and oxidative stress

“…Previous studies demonstrated that an imbalance between oxidative stress (ROS and MDA) and antioxidants (SOD and GSH‐Px) is a leading factor of MGO‐induced endothelial cell dysfunction (Narra et al, 2022). To investigate whether umbelliferone has effects in the MGO‐mediated intracellular ROS generation, HUVECs were incubated with umbelliferone (10 and 20 μM) for 2 h and subsequently exposed to MGO (500 mM) for 24 h. It was observed that MGO treatment contributed to significant increase in ROS accumulation and MDA content, which was weakened by umbelliferone (Figure 4A and B).…”

Review of the Protective Mechanism of Curcumin on Cardiovascular Disease

“…They found that Cur-rHDLs(0.2 and 0.4 µM) reduced oxidative stress and endoplasmic reticulum stress(ERS) and played a protective role in the integrity of the endothelial cell barrier. 26 AGEs also have an effect on myocardial inflammation. Sowndhar et al found that dietary curcumin could neutralize AGEs-induced adverse reactions and reduce the expression of pro-inflammatory genes.…”