Kaempferol Protects Blood Vessels From Damage Induced by Oxidative Stress and Inflammation in Association With the Nrf2/HO-1 Signaling Pathway

Abstract

Over recent years, an increasing number of studies have confirmed that the occurrence and development of vascular pathological changes are closely related to oxidative stress and the inflammatory response of the vascular endothelium. Kaempferol is the most common flavonoid compound found in fruits and vegetables. Our present research identified that kaempferol had the capability to protect the vascular endothelium in a mouse model of vascular injury and explored the specific mechanisms underlying these effects by investigating oxidative stress, the extent of cardiovascular injury, and inflammatory markers such as NF-kB, TNF-a, IL-6, and the Nrf2/HO-1 signaling pathway. Analysis showed that kaempferol reduced oxidative stress and inflammation mediated by H 2 O 2 and paraquat, respectively, both in vitro and in vivo. Furthermore, kaempferol suppressed the levels of TNF-a and IL-6, and the activation of NF-kB, in aortic tissues and human umbilical vein endothelial cells (HUVECs). Finally, we observed that kaempferol corrected the levels of antioxidants and elevated the protein levels of Nrf2 and HO-1 in aortic tissues and HUVECs. Collectively, our findings prove that kaempferol protects blood vessels from damage induced by oxidative stress and inflammation and that the Nrf2/HO-1 signaling pathway plays a key role in mediating these effects.

Kaempferol Inhibits Zearalenone-Induced Oxidative Stress and Apoptosis via the PI3K/Akt-Mediated Nrf2 Signaling Pathway: In Vitro and In Vivo Studies

“…Since KFL stimulates the Nrf2/HO-1/NQO1 pathway [ 20 ] ( Figure S1 ), we assessed whether KFL activates the Nrf2/HO-1/NQO1 pathway in ZEA-supplemented cells. Based on Western blotting and qRT-PCR, it was found that the proteins were significantly ( p < 0.05) upregulated in cells pre-treated with KFL, compared to cells treated with ZEA alone ( Figure 2 B and Figure 3 A).…”

Network Pharmacology Combined with Bioinformatics to Investigate the Mechanisms and Molecular Targets of Astragalus Radix-Panax notoginseng Herb Pair on Treating Diabetic Nephropathy

“…What is more, quercetin inhibited glomerular mesangial cell proliferation and epithelial-mesenchymal transition in DN via reactivation of the Hippo pathway and inhibition of the TGF- β /PI3K/Akt pathway, respectively [ 57 , 58 ]. Kaempferol, a natural polyflavonol, also exhibits nephroprotective effects in addition to its antioxidant and anti-inflammatory properties [ 59 ]. Studies demonstrated that kaempferol plays vital nephroprotective roles associating with inhibiting oxidative stress, proinflammatory cytokines (TNF- α and IL-1 β ), and fibrosis in DN via inhibiting hyperglycemia-induced activation RhoA/Rho-kinase [ 42 ].…”

Flavonoids and cardiovascular risk factors: a review

“…Flavonoids protect NO from inactivation and prevent eNOS uncoupling by: 1) directly scavenging superoxide anion and preventing peroxynitrite formation (54); 2) inhibiting reactive oxygen species (ROS)-producing enzymes such as NADPH oxidase, 5-lipoxygenase, cyclooxygenases (COX), myeloperoxidase, and xanthine oxidase; 3) stimulating antioxidant enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase (36,55); 4) increasing the activity of nuclear factor erythroid-2 related factor 2 (Nrf2) and up-regulating antioxidant enzymes such as NADPH:quinone oxidoreductase 1, hemeoxygenase-1, glutathione-S-transferase, and γ-glutamylcysteine ligase (56,57). In this context, several in vitro studies demonstrated the endothelium-dependency of flavonoid-induced relaxation of different vascular preparations (58).…”