The Modulation of Nrf-2/HO-1 Signaling Axis by Carthamus tinctorius L. Alleviates Vascular Inflammation in Human Umbilical Vein Endothelial Cells

Abstract

Carthamus tinctorius L., known as safflower, has been used in traditional treatment for cardiovascular, cerebrovascular, and diabetic vascular complications. We proposed to investigate how the ethanol extract of Carthamus tinctorius L. (ECT) can be used ethnopharmacologically and alleviate vascular inflammatory processes under cytokine stimulation in human vascular endothelial cells. Using the optimized HPLC method, six markers were simultaneously analyzed for quality control of ECT. Pretreatment with ECT (10–100 μg/mL) significantly reduced the increase of leukocyte adhesion to HUVEC by TNF-α in a dose-dependent manner. Cell adhesion molecules (CAMs) such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial cell selectin (E-selectin) are decreased by ECT. In addition, ECT significantly suppressed TNF-α-induced oxidative stress referring to reactive oxygen species (ROS) production. p65 NF-κB nuclear translocation and its activation were inhibited by ECT. Furthermore, pretreatment of ECT increased the HO-1 expression, and nuclear translocation of Nrf-2. These data suggest the potential role of ECT as a beneficial therapeutic herb in vascular inflammation via ROS/NF-kB pathway and the regulation of Nrf-2/HO-1 signaling axis is involved in its vascular protection. Thus, further study will be needed to clarify which compound is dominant for protection of vascular diseases.

Roles of Reactive Oxygen Species in Vascular Complications of Diabetes: Therapeutic Properties of Medicinal Plants and Food

“…Dried flowers (Honghua) and seeds of Carhamus tinctorius L. are often used to improve gynecological diseases and have good oxidation resistance [152]. The ethanol extract of flowers of C. tinctorius retarded TNF α-stimulated intracellular ROS generation by activating Nrf2/HO-1/CO signaling in HUVECs, followed by inhibiting p65 NF-κB nuclear translocation [153]. In 2K-1C hypertensive rats, the ethanolic extract of C. tinctorius suppressed the Ang II-AT1R-NADPH oxidase pathway to reduce O 2 − production in renovascular hypertension while inhibiting aortic gp91 phox overexpression as well as increasing NO bioavailability [154].…”