Components of Salvia miltiorrhiza and Panax notoginseng against OGD/R-treated injury in Pericytes via regulating PI3K/AKT and JNK/ERK/P38 signaling pathways

Abstract

Abstract Salvia miltiorrhiza (SAL) and Panax notoginseng (PNS) is widely used for the treatment of ischemic stroke. However, what components of SAL and PNS protect brain microvascular pericytes after ischemic stroke remains unclear. We evaluated protective effects and mechanisms of the components of SAL and PNS in pericytes subjected to oxygen-glucose deprivation /reoxygenation (OGD/R). Pericytes were subjected to OGD/R. Cell Counting Kit-8 (CCK-8) was performed to evaluate cell viability. ROS and SOD kits were performed to detect oxidative stress. Flow cytometry was performed to analyze cells apoptosis. Scratch assay was performed to evaluate cells migration. Western blot was performed to detected expression of apoptosis proteins, VEGF, Ang-1, PDGFRβ, PI3K/AKT and JNK/ERK/P38 signaling pathways. Results showed Salvianolic acid B (Sal B), Salvianolic acid B (Sal D), Notoginsenoside R1(R1), Ginsenoside Rb1 (Rb1) and Ginsenoside Rg1 (Rg1) increased cell viability of pericytes subjected to OGD/R, reduced the level of ROS and increased the expression of SOD. The components reduced cells apoptosis, increased the proteins level of Bcl-2/Bax, reduced the level of Cleaved caspased3/caspase3, increased cells migration and enhanced the levels of Ang-1, PDGFR-β and VEGF. The components could activate PI3K/AKT/mTOR pathway, inhibit JNK/ERK/P38 pathway. Studies found that Sal B, Sal D, R1, Rb1 and Rg1 inhibited oxidative stress and apoptosis, increased release of pro-angiogenic regulators of pericytes-related to PI3K/AKT/mTOR and JNK/ERK/P38 signaling pathways. This provides a candidate basis for the development of monomeric drugs for treatment of ischemic stroke.