Fig. 6.

Chemo-modulative properties of Naringin and Naringenin; signaling mechanisms on the vascular endothelium. The activation of the vascular endothelium in disease states entails ROS generation, the binding of cytokines, immune cells, growth factors, and disease-causing agents (such as viruses and bacteria), to the membrane of endothelial cells. These agents bind upon transmembrane receptors which activate the downstream signaling pathways as shown above. NAR and NGN when administered or ingested are metabolized and inhibit the activity of ILRs, TNFRs, RTKs, TLRs, and other intracellular kinases and transcription factors (denoted by the circular green inhibition sign). This regulates the expression of proinflammatory genes and pro-oxidant genes. Importantly, NAR and NGN modulate redox-sensitive kinases ERKs, PKC, and Akt/PKB, which activate transcription factor Nrf2. Nrf2 translocates to the nucleus where it binds the Nrf2-ARE and expresses anti-inflammatory proteins and antioxidant enzymes necessary for cell survival. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)