Recently, Nrf2/HO-1 has received extensive attention as the main regulatory pathway of intracellular defense against oxidative stress and is considered an ideal target for alleviating endothelial cell (EC) injury.
This paper aimed to summarized the natural monomers/extracts that potentially exert protective effects against oxidative stress in ECs.
A literature search was carried out regarding our topic with the keywords of \"atherosclerosis\" or \"Nrf2/HO-1\" or \"vascular endothelial cells\" or \"oxidative stress\" or \"Herbal medicine\" or \"natural products\" or \"natural extracts\" or \"natural compounds\" or \"traditional Chinese medicines\" based on classic books of herbal medicine and scientific databases including Pubmed, SciFinder, Scopus, the Web of Science, GoogleScholar, BaiduScholar, and others. Then, we analyzed the possible molecular mechanisms for different types of natural compounds in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress. In addition, perspectives for possible future studies are discussed.
These agents with protective effects against oxidative stress in ECs mainly include phenylpropanoids, flavonoids, terpenoids, and alkaloids. Most of these agents alleviate cell apoptosis in ECs due to oxidative stress, and the mechanisms are related to Nrf2/HO-1 signaling activation. However, despite continued progress in research on various aspects of natural agents exerting protective effects against EC injury by activating Nrf2/HO-1 signaling, the development of new drugs for the treatment of atherosclerosis (AS) and other CVDs based on these agents will require more detailed preclinical and clinical studies.
Our present paper provides updated information of natural agents with protective activities on ECs against oxidative stress by activating Nrf2/HO-1. We hope this review will provide some directions for the further development of novel candidate drugs from natural agents for the treatment of AS and other CVDs.

In the central nervous system, alteration of glial cell differentiation can affect brain functions. Polychlorinated biphenyls (PCBs) are persistent environmental chemical contaminants that exert neurotoxic effects in glial and neuronal cells. We examined the effects of a commercial mixture of PCBs, Aroclor1254 (A1254) on astrocytic differentiation of glial cells, using the rat C6 cell line as in vitro model. The exposure for 24 h to sub-toxic concentrations of A1254 (3 or 9 μM) impaired dibutyryl cAMP-induced astrocytic differentiation as showed by the decrease of glial fibrillary acidic protein (GFAP) protein levels and inhibition in change of cell morphology toward an astrocytic phenotype. The A1254 inhibition was restored by the addition of a protein kinase C (PKC) inhibitor, bisindolylmaleimide (bis), therefore indicating that PCBs disturbed the cAMP-induced astrocytic differentiation of C6 cells via the PKC pathway. The phosphorylation of signal transducer and activator of transcription 3 (STAT3) is essential for cAMP-induced transcription of GFAP promoter in C6 cells. Our results indicated that the exposure to A1254 (3 or 9 μM) for 24 h suppressed cAMP-induced STAT3 phosphorylation. Moreover, A1254 reduced cAMP-dependent phosphorylation of STAT3 requires inhibition of PKC activity. Together, our results suggest that PCBs induce perturbation in cAMP/PKA and PKC signaling pathway during astrocytic differentiation of glial cells.