Ginsenoside Rb1 from Panax notoginseng Suppressed TNF-α-Induced Matrix Metalloproteinase-9 via the Suppression of Double-Strand RNA-Dependent Protein Kinase (PKR)/NF-κB Pathway

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 22; p. 8050
• Main Authors: Sun, Wen-Tao, Yang, Cindy L H, Or, Terry C T, Luo, Dan, Li, James C B
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19.11.2022; MDPI
• Subjects: Bioassays; Cancer; Cardiomyocytes; Cell proliferation; Chromatography; Column chromatography; double-strand RNA-dependent protein kinase (PKR); eIF-2 Kinase; Extracellular matrix; Fractionation; Gelatinase; Gelatinase A; Gelatinase B; Gene expression; Ginsenoside Rb1; Heart; Hepatocellular carcinoma; Hepatocytes; Herbal medicine; High performance liquid chromatography; Inflammation; Kinases; Liquid chromatography; Liver; Liver cancer; Matrix metalloproteinase; matrix metalloproteinase 9; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Matrix metalloproteinases; Metalloproteinase; Metastases; Metastasis; Myoblasts; NF-kappa B - metabolism; NF-κB; NF-κB protein; NMR; Nuclear magnetic resonance; Panax notoginseng; Panax notoginseng - chemistry; Phosphorylation; Protein kinase; Proteins; Silica; Silica gel; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - pharmacology; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Ventricular Remodeling; Panax notoginseng; NF-κB; double-strand RNA-dependent protein kinase (PKR); Ginsenoside Rb1; matrix metalloproteinase 9
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27228050

Chronic inflammation is commonly accompanied by the stimulation of matrix metalloproteinases (MMPs) production and the degradation of the extracellular matrix. The overexpression of MMP-9 (Gelatinase B) highly participates in the progression of pathetic cardiac remodeling and liver cancer metastasis. (Burkill) F. H. Chen (Sanqi), a widely used traditional Chinese medicinal herb, shows myocardial protective and anti-tumor effects. In this study, we examined the inhibitory effect of different PNG extracts on tumor necrosis factor (TNF)-α-induced MMP-9 expression in cardiac myoblast H9c2 cells. Using a bioassay-guided fractionation scheme, the most active extract was fractionated by silica gel column chromatography and high-performance liquid chromatography until an active compound was obtained. The compound was identified as Ginsenoside Rb1 by nuclear magnetic resonance. Ginsenoside Rb1 inhibited TNF-α-induced MMP-9 production in both H9c2 and liver carcinoma HepG-2 cells. Interestingly, it did not affect the MMP-2 (Gelatinase A) level and the cell proliferation of the two cell lines. The inhibitory effects of Ginsenoside Rb1 may be due to its modulation of double-strand RNA-dependent protein kinase and nuclear factor kappa B signaling pathways. The results reveal the potential use of Ginsenoside Rb1 for the treatment of inflammatory and MMP-9-related cardiac remodeling and metastasis of hepatocellular carcinomas.