Inhibiting adhesion events by Panax notoginseng saponins and Ginsenoside Rbl protecting arteries via activation of Nrf2 and suppression of p38-VCAM-1 signal pathway

Ethnopharmacological relevance: Asian countries, such as China, Japan, and Korea, have witnessed a history of more than 1000 years of Panax notoginseng (Burk.) F.H. Chen's application as a famous traditional medicine for cardiovascular diseases (Zhou et al., 2004). The use of Panax notoginseng (Sang was first recorded in Bencao Gangmu, which was written by Li Shizhen, a Chinese pharmacologist of the MING dynasty, in 1578. It is included in The Plant List as one species of genus Panax (family Araliaceae). Panax notoginseng saponins (PNS) are the major active ingredients extracted from Panax notoginseng. Aim of the study: This study investigated whether PNS and the active constituent Ginsenoside Rb1 inhibits adhesion events by regulating the NF-E2-related factor 2 (Nrf2) - p38 - vascular cell adhesion molecule (VCAM)-1 pathway. Materials and methods: The AS model rats were treated once daily with PNS (100 mg/kg, i.p.) or Rb1 (40 mg/kg, i.p.), and pathological changes in the aortas were observed by electron microscopy and Sudan IV staining. The serum levels of NO, superoxide dismutase (SOD) and TINIF-alpha were measured. Upon treatment with H2O2 to induce oxidative stress, cell viability and LDH levels were measured after cells were cultured with PNS or Rbl. oxidized low density lipoprotein (oxLDL)-induced VCAM-1 and p38 protein expression and THP1 cell adhesion to ECs were assessed after treatment with PNS or Rbl. Nuclear translocation of Nrf2 and expression of its target protein heme oxygenase (HO)-1 were observed in the respective presence of PNS or Rbl. Results: Upon treatment with PNS or Rbl, pathological changes observed in the aortas of AS model rats were alleviated, and an increase in serum levels of NO and SOD and a decrease in TNF-alpha levels were observed. In vitro treatment with PNS or Rbl protected endothelial cells (ECs) from H2O2-mediated cytotoxicity, suppressed oxLDL-induced p38 and VCAM-1 protein expression and inhibited THP1 cell adhesion to ECs. Finally, PNS and Rbl treatment functionally activated Nrf2 in ECs. Conclusions: Nrf2, an EC protective system, suppresses monocyte adhesion events via the inhibition of the ROS - TNF-alpha - p38 - VCAM-1 pathway following treatment with PNS, with Rb1 specifically playing an important role among PNS active components. (C) 2016 Elsevier Ireland Ltd. All rights reserved.