Lysozyme Improves the Inhibitory Effects of Panax notoginseng Saponins on Phenotype Transformation of Vascular Smooth Muscle Cells by Binding to Ginsenoside Re

Abstract

Panax notoginseng saponins (PNS) have been used to treat cardiovascular diseases for hundreds of years in China. Lysozyme can bind to exogenous compounds and promote their activity. Nevertheless, knowledge of whether there is a synergistic role between lysozyme and PNS is far from sufficient. In this study, we show that the mixture of PNS and lysozyme synergistically inhibited platelet derived growth factor BB (PDGF-BB)-induced vascular smooth muscle cell (VSMC) viability, and in the five main components of PNS, GS-Re, but not GS-Rb1, NG-R1, GS-Rg1, or GS-Rd, reduced VSMC viability by combined application with lysozyme. Next, the supramolecular complexes formed by GS-Re and lysozyme were detected by mass spectrometry, and the binding ability increased with the concentration ratio of GS-Re to lysozyme from 4:1 to 12:1. In the supramolecular complexes, the relative contents of α-helix of lysozyme were increased, which was beneficial for stabilizing the structure of lysozyme. The 12:1 mixture of GS-Re and lysozyme (12.8 μmol/L GS-Re+1.067 μmol/L lysozyme) repressed PDGF-BB-induced VSMC viability, proliferation, and migration, which were associated with the upregulated differentiated markers and downregulated dedifferentiated markers. Finally, in CaCl2-induced rodent abdominal aortic aneurysm (AAA) models, we found that the 12:1 mixture of GS-Re and lysozyme slowed down AAA progression and reversed phenotype transformation of VSMCs. Thus, Gs-Re combined with a small amount of lysozyme may provide a novel therapeutic strategy for vascular remodeling-associated cardiovascular diseases.

SMOC2 promoted vascular smooth muscle cell proliferation, migration, and extracellular matrix degradation by activating BMP/TGF‐β1 signaling pathway

“…It is well studied that inhibiting the proliferation and migration of VSMCs could effectively inhibit the formation of AAA. ( 14 , 15 ) We found that silence of SMOC2 inhibited proliferation and migration of Ang II-treated VSMCs, whereas overexpression of SMOC2 had the opposite effect. These data demonstrated that SMOC2 may regulate the AAA developmental process by affecting the proliferation and migration of VSMCs.…”

Dipsacoside B Inhibits the Migration and Proliferation of VSMCs and Blunts Neointimal Formation by Upregulating PTEN Expression

“…Previous studies [31] have demonstrated that inhibition of excessive VSMC phenotypic switch are benefits during arterial remodeling. Studies have proven that triterpenoid saponins repressed VSMC proliferation by inhibiting phenotype transformation [17,18]. Therefore, we focus on the biomarkers to investigate whether DB exerts a role by blocking the phenotype switch of VSMC.…”

“…Report has shown that astragaloside IV can inhibit the proliferation and migration of rat VSMC by targeting CDK2 [16]. Besides, panax noto-ginseng saponins present inhibitory effects in the phenotype transformation of VSMCs and suppress abdominal aortic aneurysm progression [17]. Furthermore, ginsenoside Re inhibits VSMC proliferation induced by PDGF-BB via the eNOS/NO/cGMP pathway [18].…”

Analyzing noncovalent interactions between notoginseng saponins and lysozyme by deposition scanning intensity fading MALDI‐TOF mass spectrometry

“…Recently, it has been found the inhibitory effect of notoginseng saponins (NGS) on the proliferation of vascular smooth muscle cells, which is the pathological basis of many vascular diseases, could be promoted by binding to lysozyme. 29 Obviously, characterization and evaluation of noncovalent interaction between NGS and lysozyme is crucial to understanding their pharmacological activities. For direct MALDI analysis, an equal volume of lysozyme and NGS ligand were mixed and incubated at 38 C for 60 min.…”

“…Since it can bind with many small molecules, lysozyme is used for drug delivery in modern pharmaceutics. Recently, it has been found the inhibitory effect of notoginseng saponins (NGS) on the proliferation of vascular smooth muscle cells, which is the pathological basis of many vascular diseases, could be promoted by binding to lysozyme 29 . Obviously, characterization and evaluation of noncovalent interaction between NGS and lysozyme is crucial to understanding their pharmacological activities.…”