Puerarin protects endothelial progenitor cells from damage of angiotensin II via activation of ERK1/2‑Nrf2 signaling pathway

Abstract

Endothelial progenitor cell (EPC) dysfunction is associated with the formation of carotid atherosclerosis. It has been demonstrated that angiotensin II (Ang II) may impair the function of EPCs and puerarin, a natural product, possesses cardiovascular protective effects against oxidative stress and inflammation. Therefore, the present study aimed to investigate the beneficial effects of puerarin in Ang II‑induced EPC injury, and to elucidate the underlying mechanisms. Treatment with Ang II suppressed EPC proliferation and migration, increased the expression of the senescence marker β‑galactosidase, and the adhesion molecules intracellular adhesion molecule‑1 and vascular cell adhesion molecule‑1. However, the above effects were markedly alleviated by treatment with puerarin in a dose‑dependent manner (1, 10 and 100 µM). In addition, Ang II significantly increased reactive oxygen species production and the levels of the inflammatory cytokine tumor necrosis factor‑α and interleukin‑6. Notably, these effects were reversed by puerarin. However, it was identified that the impaired EPC functions were due to inhibition of the phosphorylation of extracellular signal‑regulated kinase 1 and 2 (ERK1/2) and the degradation of nuclear factor erythroid 2 like 2 (Nrf2), and treatment with puerarin activated the ERK1/2‑Nrf2 signaling pathway. The results of the present study indicated that puerarin protected Ang II‑induced EPC dysfunction via activation of the ERK1/2‑Nrf2 signaling pathway.

Endothelial Progenitor Cells: New Targets for Therapeutics for Inflammatory Conditions With High Cardiovascular Risk

“…In parallel, there is evidence that MACs are also of utmost importance in their contribution to angiogenesis, tissue regeneration and endothelial repair ( 22 , 23 ), where these precursor cells exert paracrine and trophic effects that influence the host microenvironment ( 24 , 25 ). The following sections will describe mechanisms underpinning vascular dysfunction in inflammatory conditions with high risk of cardiovascular disease (CVD) and consider potential therapeutic options aimed at improving progenitor cell reparative function ( 26 , 27 ) as a novel approach to exploit endogenous repair processes.…”

Puerarin protects vascular smooth muscle cells from oxidized low‑density lipoprotein‑induced reductions in viability via inhibition of the p38 MAPK and JNK signaling pathways

“…Puerarin, a major isoflavone isolated from the root of Pueraria lobata, has been reported to treat various cardiovascular diseases, including arterial hypertension, angina, myocardial infarction and arrhythmia (26)(27)(28). Puerarin has anti-atherosclerotic activity in diet-induced atherosclerosis in rabbits and rats (17,18).…”

Puerarin alters the function of monocytes/macrophages and exhibits chondroprotection in mice

“…Puerarin has been hypothesized to act in an arginase 2-dependent manner, a mitochondrial enzyme, via modulation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-associated oxidative stress (6,(11)(12)(13). In addition, puerarin alters the production of innate immune cells by regulating the differentiation of progenitor cells via estrogen receptors (14). Previous studies reported the protective effects of puerarin on the viability and function of endothelial progenitor cells derived from bone borrow and peripheral blood (10,14).…”

“…In addition, puerarin alters the production of innate immune cells by regulating the differentiation of progenitor cells via estrogen receptors (14). Previous studies reported the protective effects of puerarin on the viability and function of endothelial progenitor cells derived from bone borrow and peripheral blood (10,14). Furthermore, puerarin exhibits ameliorative effects in various inflammatory disorders via inhibiting the degranulation of mast cells, reducing monocyte adhesion to endothelial cells and modifying chemotactic agent expression in cardiac fibrotic tissue (15)(16)(17).…”

“…Furthermore, puerarin exhibits ameliorative effects in various inflammatory disorders via inhibiting the degranulation of mast cells, reducing monocyte adhesion to endothelial cells and modifying chemotactic agent expression in cardiac fibrotic tissue (15)(16)(17). Innate immune signal transduction pathways, including nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), mitogen-activated protein kinase and extracellular signal-regulated kinase signaling may be affected by treatment with puerarin (14,18,19).…”