Ginsenoside Rg1 prevents vascular intimal hyperplasia involved by SDF-1α/CXCR4, SCF/c-kit and FKN/CX3CR1 axes in a rat balloon injury

• Published in: Journal of ethnopharmacology 2020-10, Vol.260, p.113046-113046, Article 113046
• Main Authors: Hu, Anling, Shuai, Zhiqin, Liu, Jiajia, Huang, Bo, Luo, Yunmei, Deng, Jiang, Liu, Jie, Yu, Limei, Li, Lisheng, Xu, Shangfu
• Format: Article
• Language: English
• Subjects: Angioplasty, Balloon; Animals; Carotid Artery Injuries - etiology; Carotid Artery Injuries - metabolism; Carotid Artery Injuries - pathology; Carotid Artery Injuries - prevention & control; Carotid Artery, Common - drug effects; Carotid Artery, Common - metabolism; Carotid Artery, Common - pathology; Chemokine CX3CL1 - metabolism; Chemokine CXCL12 - metabolism; CX3C Chemokine Receptor 1 - metabolism; Disease Models, Animal; FKN/CX3CR1; Ginsenoside Rg1; Ginsenosides - pharmacology; Hyperplasia; Male; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - injuries; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Neointima; Proto-Oncogene Proteins c-kit - metabolism; Rats, Sprague-Dawley; Receptors, CXCR4 - metabolism; SCF/c-Kit; SDF-1α/CXCR4; Signal Transduction; Smooth muscle progenitor cells; Stem Cell Factor - metabolism
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2020.113046

Panax ginseng C. A. Mey. is a traditional tonic that has been used for thousands of years, and has positive effects on vascular diseases. Ginsenoside Rg1 (GS-Rg1) is one of the active ingredients of Panax ginseng C. A. Mey. and has been shown to have beneficial effects against ischemia/reperfusion injury. Our previously study has found that GS-Rg1 can mobilize bone marrow stem cells and inhibit vascular smooth muscle proliferation and phenotype transformation. However, pharmacological effects and mechanism of GS-Rg1 in inhibiting intimal hyperplasia is still unknown. This study was aimed to investigate whether GS-Rg1 prevented vascular intimal hyperplasia, and the involvement of stromal cell-derived factor-1α (SDF-1α)/CXCR4, stem cell factor (SCF)/c-kit and fractalkine (FKN)/CX3CR1 axes. Rats were operated with carotid artery balloon injury. The treatment groups were injected with 4, 8 and 16 mg/kg of GS-Rg1 for 14 days. The degree of intimal hyperplasia was evaluated by histopathological examination. The expression of α-SMA (α-smooth muscle actin) and CD133 were detected by double-label immunofluorescence. Serum levels of SDF-1α, SCF and soluble FKN (sFKN) were detected by enzyme linked immunosorbent assay (ELISA). The protein expressions of SCF, SDF-1α and FKN, as well as the receptors c-kit, CXC chemokine receptor type 4 (CXCR4) and CX3C chemokine receptor type 1 (CX3CR1) were detected by immunochemistry. GS-Rg1 reduced intimal hyperplasia by evidence of the values of NIA, the ratio of NIA/MA, and the ratio of NIA/IELA and the ratio of NIA/LA, especially in 16 mg/kg group. Furthermore, GS-Rg1 8 mg/kg group and 16 mg/kg group decreased the protein expressions of the SDF-1α/CXCR4, SCF/c-kit and FKN/CX3CR1 axes in neointima, meanwhile GS-Rg1 8 mg/kg group and 16 mg/kg group also attenuated the expressions of SDF-1α, SCF and sFKN in serum. In addition, the expression of α-SMA and CD133 marked smooth muscle progenitor cells (SMPCs) was decreased after GS-Rg1 treatment. GS-Rg1 has a positive effect on inhibiting vascular intimal hyperplasia, and the underlying mechanism is related to inhibitory expression of SDF-1α/CXCR4, SCF/c-kit and FKN/CX3CR1 axes. [ [Display omitted] ] •GS-Rg1 reduced the degree of intimal hyperplasia induced by balloon injury.•SDF-1α/CXCR4, SCF/c-kit and FKN/CX3CR1 axes were involved in the effect of GS-Rg1.•SMPCs might be related to the effect of GS-Rg1 on inhibiting intimal hyperplasia.