Inhibiting adhesion events by Panax notoginseng saponins and Ginsenoside Rb1 protecting arteries via activation of Nrf2 and suppression of p38 - VCAM-1 signal pathway

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• 作者：Jishan Fan^a ; Danning Liu^b ; Cuiyao He^a ; Xiaohui Li^c ; ^{river080@sohu.com" class="auth_mail" title="E-mail the corresponding author} ; Fengtian He^d ; ^{steven2535@sina.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AS ; atherosclerosis ; PNS ; Panax notoginseng saponins ; Rb1 ; Ginsenoside Rb1 ; Nrf2 ; NF-E2-related factor 2 ; p38 ; p38 mitogen-activated protein kinase ; VCAM-1 ; vascular cell adhesion molecule-1 ; oxLDL ; oxidized low density lipoprotein ; EC ; endothelial cells ; HO1 ; heme oxygenase-1 ; SFN ; sulforaphane ; HUVEC ; human umbilical vein endothelial cells ; H2O2 ; hydrogen peroxide
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：4 November 2016
• 年：2016
• 卷：192
• 期：Complete
• 页码：423-430
• 全文大小：2746 K

文摘

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 (Sanqi) 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 TNF-α were measured. Upon treatment with H₂O₂ to induce oxidative stress_, cell viability and LDH levels were measured after cells were cultured with PNS or Rb1. 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 Rb1. Nuclear translocation of Nrf2 and expression of its target protein heme oxygenase (HO)-1 were observed in the respective presence of PNS or Rb1.

Results

Upon treatment with PNS or Rb1, 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-α levels were observed. In vitro treatment with PNS or Rb1 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 Rb1 treatment functionally activated Nrf2 in ECs.

Conclusions

Nrf2, an EC protective system, suppresses monocyte adhesion events via the inhibition of the ROS – TNF-α – p38 – VCAM-1 pathway following treatment with PNS, with Rb1 specifically playing an important role among PNS active components.