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Ginsenoside Rb1 from Panax notoginseng Suppressed TNF-α-Induced Matrix Metalloproteinase-9 via the Suppression of
Wen-Tao Sun1, Cindy L H Yang2, Terry C T Or2
1School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao 266071, China.
Abstract:
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. Panax notoginseng (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.
Insights
Ginsenoside Rb1 from Panax notoginseng inhibits tumor necrosis factor-α-induced matrix metalloproteinase-9 (MMP-9) production. This compound shows potential for treating inflammatory conditions and cancer metastasis.
Area of Science:
- Pharmacology
- Biochemistry
- Traditional Chinese Medicine
Background:
- Chronic inflammation stimulates matrix metalloproteinases (MMPs), leading to extracellular matrix degradation.
- Overexpression of MMP-9 (Gelatinase B) is implicated in cardiac remodeling and liver cancer metastasis.
- Panax notoginseng (Sanqi) is a traditional Chinese herb with known myocardial protective and anti-tumor properties.
Purpose of the Study:
- To investigate the inhibitory effects of Panax notoginseng extracts on tumor necrosis factor-α (TNF-α)-induced MMP-9 expression.
- To identify the active compound responsible for MMP-9 inhibition.
- To explore the therapeutic potential of the identified compound in inflammatory and metastatic conditions.
Main Methods:
- Bioassay-guided fractionation of Panax notoginseng extracts.
- Silica gel column chromatography and high-performance liquid chromatography for compound isolation.
- Identification of the active compound using nuclear magnetic resonance spectroscopy.
- Assay of MMP-9 production in H9c2 and HepG-2 cells stimulated with TNF-α.
Main Results:
- Ginsenoside Rb1 was isolated and identified as the active compound.
- Ginsenoside Rb1 significantly inhibited TNF-α-induced MMP-9 production in both cardiac myoblast H9c2 and liver carcinoma HepG-2 cells.
- Ginsenoside Rb1 did not affect MMP-2 levels or cell proliferation in either cell line.
- Inhibitory effects are potentially mediated by modulation of protein kinase and nuclear factor kappa B signaling pathways.
Conclusions:
- Ginsenoside Rb1 demonstrates potent inhibition of MMP-9 production.
- This suggests a potential therapeutic role for Ginsenoside Rb1 in managing inflammatory diseases and preventing metastasis of hepatocellular carcinomas.
- Further research into its signaling pathway modulation could elucidate its mechanisms of action.
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